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Borkar SA, Yin L, Venturi GM, Shen J, Chang KF, Fischer BM, Nepal U, Raplee ID, Sleasman JW, Goodenow MM. Youth Who Control HIV on Antiretroviral Therapy Display Unique Plasma Biomarkers and Cellular Transcriptome Profiles Including DNA Repair and RNA Processing. Cells 2025; 14:285. [PMID: 39996757 PMCID: PMC11853983 DOI: 10.3390/cells14040285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/24/2025] [Accepted: 02/12/2025] [Indexed: 02/26/2025] Open
Abstract
Combination antiretroviral therapy (ART) suppresses detectible HIV-1 replication, but latent reservoirs and persistent immune activation contribute to residual viral-associated morbidities and potential viral reactivation. youth with HIV (YWH) virally suppressed on ART early in infection before CD4 T cell decline with fewer comorbidities compared to adults represent a critical population for identifying markers associated with viral control and predictors of viral breakthrough. This study employed a multi-omics approach to evaluate plasma biomarkers and cellular gene expression profiles in 52 participants, including 27 YWH on ART for 144 weeks and 25 youth with no infection (NI) (ages 18-24). Among the 27 YWH, 19 were virally suppressed (VS; <50 RNA copies/mL), while eight were non-suppressed (VNS; >50 RNA copies/mL). VS YWH displayed unique bioprofiles distinct from either VNS or NI. Early viral suppression mitigates inflammatory pathways and normalizes key biomarkers associated with HIV-related comorbidities. Genes upregulated in pathways linked to cellular homeostasis such as DNA repair, RNA processing, and transcription regulation may diminish viral breakthrough and maintain sustained HIV control on ART. Candidate markers and putative molecular mechanisms were identified, offering potential therapeutic targets to limit viral persistence, enhance HIV treatment strategies, and pave the way for improved clinical outcomes.
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Affiliation(s)
- Samiksha A. Borkar
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - Li Yin
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - Guglielmo M. Venturi
- Division of Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; (G.M.V.); (B.M.F.); (J.W.S.)
| | - Jerry Shen
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - Kai-Fen Chang
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - Bernard M. Fischer
- Division of Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; (G.M.V.); (B.M.F.); (J.W.S.)
| | - Upasana Nepal
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - Isaac D. Raplee
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
| | - John W. Sleasman
- Division of Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA; (G.M.V.); (B.M.F.); (J.W.S.)
| | - Maureen M. Goodenow
- Molecular HIV and Host Interactions Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20894, USA; (L.Y.); (J.S.); (K.-F.C.); (U.N.); (I.D.R.); (M.M.G.)
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Sheets K, Baker JV. HIV and Inflamm-Aging: How Do We Reach the Summit of Healthy Aging? TOPICS IN ANTIVIRAL MEDICINE 2024; 32:589-596. [PMID: 39765238 PMCID: PMC11737810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 01/18/2025]
Abstract
People with HIV (PWH) are living longer and experiencing a greater burden of morbidity from non-AIDS-defining conditions. Chronically treated HIV disease is associated with ongoing systemic inflammation that contributes to the development of chronic conditions (eg, cardiovascular disease) and geriatric syndromes (eg, frailty). Apart from HIV disease, a progressive increase in systemic inflammation is a characteristic feature of biologic aging, a process described as "inflammaging." Inflamm-aging is driven by persistent antigen stimulation and stress, leading to an immune profile characterized by elevated levels of blood inflammatory markers and cellular activation and senescence. Chronic HIV disease is hypothesized to accentuate the immune profile of inflamm-aging, in part through viral persistence in lymphatic tissues, permanent injury impairing immune recovery, the presence of copathogens, gut dysbiosis and microbial translocation, and chromosomal and genetic alterations associated with immune activation. Few strategies exist for safe and effective modulation of systemic inflammation among older PWH. The strongest current evidence supports aggressive management of modifiable risk factors such as lipids, blood pressure, and levels of physical activity. Future inflamm-aging research should be directed toward advancing the implementation of proven approaches, such as physical activity, as well as studying novel mechanisms of, and treatments for, inflamm-aging among PWH.
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Affiliation(s)
- Kerry Sheets
- Hennepin Healthcare, Minneapolis, Minnesota, and University of Minnesota, Minneapolis
| | - Jason V. Baker
- Hennepin Healthcare, Minneapolis, Minnesota, and University of Minnesota, Minneapolis
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Okafor CN, Somasunderam A, Lake JE, Gelfond J, Javanbakht M, Gorbach P, Shoptaw S, Schmitz J. Cannabis Use and Biomarkers of Inflammation, Immune Activation, and Microbial Translocation in Persons with HIV. Cannabis Cannabinoid Res 2024; 9:e1579-e1587. [PMID: 38335314 PMCID: PMC11685291 DOI: 10.1089/can.2023.0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/12/2024] Open
Abstract
Background: The relationship between cannabis and inflammation among persons with HIV (PWH) remains unclear. We examined whether the cannabis metabolite 11-nor-9-carboxy THC (THC-COOH) is associated with lower levels of plasma biomarkers of inflammation, immune activation, and microbial translocation in PWH. We hypothesized that cannabis use would be associated with lower levels of plasma inflammatory biomarkers than noncannabis use. Methods: We quantified THC-COOH in plasma, with THC-COOH levels between 5.1-69.9 μg/L and ≥70 μg/L being classified as moderate and heavy cannabis use, respectively, with noncannabis use defined as undetected THC-COOH. We measured a panel of plasma biomarkers of inflammation (interleukin [IL]-1-β, tumor necrosis factor-alpha, IL-18, IL-6, and C-reactive protein), immune activation (CD14 and CD163), and microbial translocation (iFABP2 and lipopolysaccharide binding protein [LBP]), with all biomarkers collected on the same day. We used a cross-sectional design and linear regression models to test whether cannabis use is associated with lower biomarker levels. Results: Participants were (N=107) sexual minority men with HIV (median age=32 years, IQR=28, 38), of whom 65% were virally suppressed; 36%, 44%, and 20% were classified as nonuse, moderate, and heavy cannabis, respectively. In linear regression models adjusted for viral suppression, stimulant use, and CD4 counts, heavy cannabis use was significantly associated with lower levels of log10 LBP (β=-0.14, 95% confidence interval: -0.24 to -0.04; false discovery rate=0.0029; partial eta squared=0.07) than noncannabis users. No precise associations were observed for other biomarkers (all p>0.05). Conclusions: Our findings suggest that cannabis use may be associated with lower plasma LBP. Further work is needed to clarify the relationship between cannabis use and biomarkers of microbial translocation in PWH.
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Affiliation(s)
- Chukwuemeka N. Okafor
- Division of Infectious Diseases, Department of Medicine, Long School of Medicine, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
| | - Anoma Somasunderam
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Jordan E. Lake
- Division of Infectious Disease, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Jonathan Gelfond
- Department of Population Health Sciences, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
| | - Marjan Javanbakht
- Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
| | - Pamina Gorbach
- Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
| | - Steven Shoptaw
- Department of Family Medicine, University of California Los Angeles, Los Angeles, California, USA
| | - Joy Schmitz
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
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Nazari I, Feinstein MJ. Evolving mechanisms and presentations of cardiovascular disease in people with HIV: implications for management. Clin Microbiol Rev 2024; 37:e0009822. [PMID: 38299802 PMCID: PMC10938901 DOI: 10.1128/cmr.00098-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024] Open
Abstract
People with HIV (PWH) are at elevated risk for cardiovascular diseases (CVDs), including myocardial infarction, heart failure, and sudden cardiac death, among other CVD manifestations. Chronic immune dysregulation resulting in persistent inflammation is common among PWH, particularly those with sustained viremia and impaired CD4+ T cell recovery. This inflammatory milieu is a major contributor to CVDs among PWH, in concert with common comorbidities (such as dyslipidemia and smoking) and, to a lesser extent, off-target effects of antiretroviral therapy. In this review, we discuss the clinical and mechanistic evidence surrounding heightened CVD risks among PWH, implications for specific CVD manifestations, and practical guidance for management in the setting of evolving data.
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Affiliation(s)
- Ilana Nazari
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Matthew J. Feinstein
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Division of Cardiology in the Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Foldyna B, Mayrhofer T, Zanni MV, Lyass A, Barve R, Karady J, McCallum S, Burdo TH, Fitch KV, Paradis K, Fulda ES, Diggs MR, Bloomfield GS, Malvestutto CD, Fichtenbaum CJ, Aberg JA, Currier JS, Ribaudo HJ, Hoffmann U, Lu MT, Douglas PS, Grinspoon SK. Pericoronary Adipose Tissue Density, Inflammation, and Subclinical Coronary Artery Disease Among People With HIV in the REPRIEVE Cohort. Clin Infect Dis 2023; 77:1676-1686. [PMID: 37439633 PMCID: PMC10724469 DOI: 10.1093/cid/ciad419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 06/30/2023] [Accepted: 07/10/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population. METHODS In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates. RESULTS Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001). CONCLUSIONS Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.
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Affiliation(s)
- Borek Foldyna
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Thomas Mayrhofer
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Health Economics, School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
| | - Markella V Zanni
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Asya Lyass
- Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA
| | - Radhika Barve
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Julia Karady
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Sara McCallum
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Tricia H Burdo
- Department of Microbiology, Immunology, and Inflammation and Center for NeuroVirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA
| | - Kathleen V Fitch
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Kayla Paradis
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Evelynne S Fulda
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Marissa R Diggs
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Gerald S Bloomfield
- Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA
| | - Carlos D Malvestutto
- Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA
| | - Carl J Fichtenbaum
- Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Judith A Aberg
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Judith S Currier
- Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
| | - Heather J Ribaudo
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Udo Hoffmann
- Innovative Imaging Consulting LLC, Waltham, Massachusetts, USA
| | - Michael T Lu
- Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Pamela S Douglas
- Department of Medicine (Cardiology), Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Steven K Grinspoon
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Mushin AS, Trevillyan JM, Lee SJ, Hearps AC, Hoy JF. Factors associated with the development of coronary artery disease in people with HIV. Sex Health 2023; 20:470-474. [PMID: 37394729 DOI: 10.1071/sh23043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 06/13/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND People living with HIV (PLHIV) are at increased risk for coronary artery disease (CAD). This study aimed to describe the features associated with CAD in PLHIV. METHODS A case ([n =160] PLHIV with CAD) control ([n =317] PLHIV matched by age and sex without CAD) study was performed at the Alfred Hospital, Melbourne, Australia (January 1996 and December 2018). Data collected included CAD risk factors, duration of HIV infection, nadir and at-event CD4+ T-cell counts, CD4:CD8 ratio, HIV viral load, and antiretroviral therapy exposure. RESULTS Participants were predominantly male (n =465 [97.4%]), with a mean age of 53years. Traditional risk factors associated with CAD in univariate analysis included hypertension (OR 11.4 [95%CI 5.01, 26.33], P <0.001), current cigarette smoking (OR 2.5 [95% CI 1.22, 5.09], P =0.012), and lower high-density lipoprotein cholesterol (OR 0.14 [95%CI 0.05, 0.37], P <0.001). There was no association between duration of HIV infection, nadir or current CD4 cell count. However, current and ever exposure to abacavir (cases: 55 [34.4%]; controls: 79 [24.9%], P =0.023 and cases: 92 [57.5%]; controls: 154 [48.6%], P =0.048, respectively) was associated with CAD. In conditional logistic regression analysis, current abacavir use, current smoking, and hypertension remained significantly associated (aOR=1.87 [CI=1.14, 3.07], aOR=2.31 [1.32, 4.04], and aOR=10.30 [5.25, 20.20] respectively). CONCLUSION Traditional cardiovascular risk factors and exposure to abacavir were associated with CAD in PLHIV. This study highlights that aggressive management of cardiovascular risk factors remains critical for reducing risk in PLHIV.
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Affiliation(s)
- Ari S Mushin
- Department of Infectious Diseases, Monash University, Melbourne, Vic., Australia
| | - Janine M Trevillyan
- Department of Infectious Diseases, Austin Health, Melbourne, Vic., Australia; and Department of Infectious Diseases at the Peter Doherty Institute of Infection and Immunity, University of Melbourne, Melbourne, Vic., Australia
| | - Sue J Lee
- Department of Infectious Diseases, Monash University, Melbourne, Vic., Australia; and Department of Infectious Diseases, Alfred Hospital, Melbourne, Vic., Australia
| | - Anna C Hearps
- Department of Infectious Diseases, Monash University, Melbourne, Vic., Australia; and Life Sciences Discipline, Burnet Institute, Melbourne, Vic., Australia
| | - Jennifer F Hoy
- Department of Infectious Diseases, Monash University, Melbourne, Vic., Australia; and Department of Infectious Diseases, Alfred Hospital, Melbourne, Vic., Australia
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Temu TM, Polyak SJ, Wanjalla CN, Mandela NA, Dabee S, Mogaka JN, Masyuko S, Longernecker C, Shakil S, Chohan B, Page ST, Lacourse SM, Gitura B, Crothers K, Oyugi J, Jaspan H, Farquhar C, Zifodya JS. Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy. AIDS 2023; 37:1065-1075. [PMID: 36928263 PMCID: PMC10155699 DOI: 10.1097/qad.0000000000003523] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/24/2023] [Accepted: 02/09/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults. METHODS We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI-, HIV-LTBI+, HIV-LTBI-). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors. RESULTS Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models ( P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants ( P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV-LTBI- ( P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4 + T-cell count and ART duration. CONCLUSIONS Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.
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Affiliation(s)
- Tecla M. Temu
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Stephen J. Polyak
- Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington
| | | | | | - Smritee Dabee
- Center for Infectious Disease Research, Seattle Biomedical Research Institute
| | - Jerusha N. Mogaka
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | | | - Chris Longernecker
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Medicine, University of Washington
| | - Saate Shakil
- Department of Medicine, University of Washington
| | - Bhavna Chohan
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | | | - Sylvia M. Lacourse
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Medicine, University of Washington
| | | | | | - Julius Oyugi
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Heather Jaspan
- Center for Infectious Disease Research, Seattle Biomedical Research Institute
| | - Carey Farquhar
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Medicine, University of Washington
- Veterans Affairs Puget Sound Healthcare System, Seattle, Washington
| | - Jerry S. Zifodya
- Department of Medicine, Tulane University School of Medicine, New Orleans, Lousiana, USA
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Abstract
PURPOSE OF REVIEW We review the intersection between the HIV and COVID-19 pandemics, particularly the impact of HIV infection on the development of severe COVID-19. RECENT FINDINGS Studies early in the COVID-19 pandemic did not find a clear link between HIV infection and increased COVID-19 severity or mortality. People with HIV (PWH) were more likely to have severe COVID-19, but much of the risk for worse outcomes was related to high rates of comorbidities and social determinants of health. Although comorbidities and social determinants of health are certainly critically important reasons for severe COVID-19 among PWH, recent large studies have found HIV infection - particularly when the CD4 cell count is low or HIV RNA is not suppressed - is an independent risk factor for COVID-19 severity. The link between HIV and severe COVID-19 highlights the need to diagnose and treat HIV as well as the importance of COVID-19 vaccination and treatment among PWH. SUMMARY People with HIV have faced increased challenges during the COVID-19 pandemic because of high rates of comorbidities and social determinants of health as well as the impact of HIV on COVID-19 severity. Information on the intersection of the two pandemics has been crucial to improving care for people with HIV.
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Affiliation(s)
- Kathleen W Miller
- Department of Infectious Disease, Massachusetts General Hospital, Boston, Massachusetts, USA
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Dalli J, Kitch D, O'Brien MP, Hunt PW, Funderburg N, Moisi D, Gupta A, Brown TT, Tien PC, Aberg JA, Shivakoti R. Pro-inflammatory and pro-resolving lipid mediators of inflammation in HIV: effect of aspirin intervention. EBioMedicine 2023; 89:104468. [PMID: 36791659 PMCID: PMC10025757 DOI: 10.1016/j.ebiom.2023.104468] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/25/2022] [Accepted: 01/24/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established; further aspirin reduces CVD risk in the general population through production of some of these anti-inflammatory lipid mediators, but they have not been studied in PWH. METHODS We evaluated the relationship between plasma lipid mediators (i.e. 50 lipid mediators including classic eicosanoids and specialized pro-resolving mediators (SPMs)) and HIV status; and the impact of aspirin in PWH on regulating these autacoids. Plasma samples were obtained from 110 PWH receiving antiretroviral therapy (ART) from a randomized trial of aspirin (ACTG-A5331) and 107 matched SN samples (MACS-WIHS Combined Cohort). FINDINGS PWH had lower levels of arachidonic acid-derived pro-inflammatory prostaglandins (PGs: PGE2 and PGD2) and thromboxanes (Tx: TxB2), and higher levels of select pro-resolving lipid mediators (e.g. RvD4 and MaR2n-3 DPA) compared to SN. At the interval tested, aspirin intervention was observed to reduced PGs and Tx, and while we did not observe an increase in aspirin triggered mediators, we observed the upregulation of other SPM in aspirin treated PWH, namely MaR2n-3 DPA. INTERPRETATION Together these observations demonstrate that plasma lipid mediators profiles, some with links to systemic inflammation and CVD risk, become altered in PWH. Furthermore, aspirin intervention did not increase levels of aspirin-triggered pro-resolving lipid mediators, consistent with other reports of an impaired aspirin response in PWH. FUNDING NIH.
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Affiliation(s)
- Jesmond Dalli
- William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Center for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK
| | - Douglas Kitch
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA
| | | | - Peter W Hunt
- Department of Medicine, University of California, San Francisco School of Medicine, USA and Department of Veterans Affairs Medical Center, San Francisco, USA
| | - Nicholas Funderburg
- Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, Ohio State University, Columbus, USA
| | - Daniela Moisi
- Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, USA
| | - Amita Gupta
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, USA
| | - Todd T Brown
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco School of Medicine, USA and Department of Veterans Affairs Medical Center, San Francisco, USA
| | - Judith A Aberg
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Rupak Shivakoti
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
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Adedokun TA, Kwaghe VG, Adedokun O, Badru T, Odili AN, Alfa J, Kolade-Yunusa HO, Ojji DB. Prevalence and risk factors for subclinical atherosclerosis amongst adults living with HIV in University of Abuja Teaching Hospital, Gwagwalada. FRONTIERS IN REPRODUCTIVE HEALTH 2023; 5:1092211. [PMID: 36819143 PMCID: PMC9935581 DOI: 10.3389/frph.2023.1092211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 01/10/2023] [Indexed: 02/05/2023] Open
Abstract
Background Subclinical atherosclerosis characterizes cardiovascular diseases (CVD), and Human Immunodeficiency Virus (HIV) infection and antiretroviral therapy (ART) are identified risk factors for atherosclerosis. Meanwhile, data on HIV and atherosclerosis in Nigeria are limited. Objectives We sought to estimate the prevalence of subclinical atherosclerosis and associated risk factors amongst adult persons living with HIV/AIDS (PLHIV) enrolled at University of Abuja Teaching Hospital, Gwagwalada, Abuja (UATH). Methods This was a cross-sectional study of 277 consecutively selected PLHIV ≥18 years enrolled for HIV care and treatment at UATH. Pretested structured questionnaire was used to collect data from consenting ART-experienced and ART-naïve patients on risk factors of atherosclerosis. Carotid intima media thickness (CIMT) ≥0.71 mm as measured by Doppler ultrasonography was used to identify patients with sub-clinical atherosclerosis. Two logistic regression models with (Model-A) and without (Model-B) traditional risk factors were fitted to identify risk factors of subclinical atherosclerosis. Results Participants' mean age was 39.44 ± 10.71 years with female preponderance (64.26%). Overall prevalence of subclinical atherosclerosis was 43.32% (62.25% in ART-experienced). Model-A identified male sex [AOR 4.33(1.74-10.76), p = 0.002], advancing age [30-39 years AOR 5.95(1.31-26.96), p = 0.021]; ≥40 years AOR 19.51(4.30-88.56), p ≤ 0.001), advancing HIV infection [≥WHO stage II AOR 4.19(1.11-15.92), p = 0.035], hypercholesterolemia [AOR 3.88(1.47-10.25), p ≤ 0.001] and ≥5 year duration on ART [AOR 9.05(3.16-25.92), p ≤ 0.001] as risk factors of subclinical atherosclerosis. In Model-B (excluding traditional risk factors) on the other hand, advancing HIV infection [≥WHO stage II AOR 3.93(1.19-13.042), p = 0.025] and duration on ART [≥5 years AOR 11.43(4.62-28.29), p = 0.001] were found as risk factors of subclinical atherosclerosis. Conclusion Subclinical atherosclerosis was higher in ART-experienced patients, and this was irrespective of presence or absence of traditional risk factors. And advancing HIV disease and duration on ART were found as significant risk factors for subclinical atherosclerosis. We therefore recommend routine CVD risk screening in PLHIV.
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Affiliation(s)
- Taiwo A. Adedokun
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria,Correspondence: Taiwo A. Adedokun
| | - Vivian G. Kwaghe
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria
| | - Oluwasanmi Adedokun
- Center for International Health, Education, and Biosecurity (Ciheb), Maryland Global Initiatives Corporation (MGIC) - an Affiliate of University of Maryland Baltimore, Abuja, Nigeria
| | - Titilope Badru
- Strategic Information Department, FHI360, Abuja, Nigeria
| | - Augustine N. Odili
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria
| | - Jacob Alfa
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria
| | - Hadijat O. Kolade-Yunusa
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria
| | - Dike B. Ojji
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, FCT, Nigeria
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11
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Perkins MV, Joseph S, Dittmer DP, Mackman N. Cardiovascular Disease and Thrombosis in HIV Infection. Arterioscler Thromb Vasc Biol 2023; 43:175-191. [PMID: 36453273 PMCID: PMC10165851 DOI: 10.1161/atvbaha.122.318232] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/18/2022] [Indexed: 12/03/2022]
Abstract
HIV infection has transitioned from an acute, fatal disease to a chronic one managed by antiretroviral therapy. Thus, the aging population of people living with HIV (PLWH) continues to expand. HIV infection results in a dysregulated immune system, wherein CD4+ T cells are depleted, particularly in the gastrointestinal tract, disrupting the gut epithelial barrier. Long-term HIV infection is associated with chronic inflammation through potentially direct mechanisms caused by viral replication or exposure to viral proteins and indirect mechanisms resulting from increased translocation of microbial products from the intestine or exposure to antiretroviral therapy. Chronic inflammation (as marked by IL [interleukin]-6 and CRP [C-reactive protein]) in PLWH promotes endothelial cell dysfunction and atherosclerosis. PLWH show significantly increased rates of cardiovascular disease, such as myocardial infarction (risk ratio, 1.79 [95% CI, 1.54-2.08]) and stroke (risk ratio, 2.56 [95% CI, 1.43-4.61]). In addition, PLWH have increased levels of the coagulation biomarker D-dimer and have a two to ten-fold increased risk of venous thromboembolism compared with the general population. Several small clinical trials analyzed the effect of different antithrombotic agents on platelet activation, coagulation, inflammation, and immune cell activation. Although some markers for coagulation were reduced, most agents failed to reduce inflammatory markers in PLWH. More studies are needed to understand the underlying mechanisms driving inflammation in PLWH to create better therapies for lowering chronic inflammation in PLWH. Such therapies can potentially reduce atherosclerosis, cardiovascular disease, and thrombosis rates in PLWH and thus overall mortality in this population.
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Affiliation(s)
- Megan V. Perkins
- UNC Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Sarah Joseph
- UNC Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Dirk P. Dittmer
- UNC Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Nigel Mackman
- UNC Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Hematology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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12
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Zanni MV, Foldyna B, McCallum S, Burdo TH, Looby SE, Fitch KV, Fulda ES, Autissier P, Bloomfield GS, Malvestutto CD, Fichtenbaum CJ, Overton ET, Aberg JA, Erlandson KM, Campbell TB, Ellsworth GB, Sheth AN, Taiwo B, Currier JS, Hoffmann U, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK. Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States. Clin Infect Dis 2023; 76:323-334. [PMID: 36101518 PMCID: PMC9839188 DOI: 10.1093/cid/ciac767] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/26/2022] [Accepted: 09/12/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. METHODS REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. RESULTS The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055). CONCLUSIONS Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).
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Affiliation(s)
- Markella V Zanni
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Borek Foldyna
- Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Sara McCallum
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Tricia H Burdo
- Department of Microbiology, Immunology, and Inflammation and Center for NeuroVirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA
| | - Sara E Looby
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Yvonne L. Munn Center for Nursing Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Kathleen V Fitch
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Evelynne S Fulda
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Patrick Autissier
- Department of Biology , Boston College, Chestnut Hill, Massachusetts, USA
| | - Gerald S Bloomfield
- Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA
| | - Carlos D Malvestutto
- Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA
| | - Carl J Fichtenbaum
- Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Edgar T Overton
- Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA
| | - Judith A Aberg
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Kristine M Erlandson
- Department of Medicine, Division of Infectious Disease, University of Colorado—Anschutz Medical Campus, Aurora, Colorado, USA
| | - Thomas B Campbell
- Department of Medicine, Division of Infectious Disease, University of Colorado—Anschutz Medical Campus, Aurora, Colorado, USA
| | - Grant B Ellsworth
- Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA
| | - Anandi N Sheth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Babafemi Taiwo
- Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois, USA
| | - Judith S Currier
- Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
| | - Udo Hoffmann
- Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Michael T Lu
- Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Pamela S Douglas
- Duke University Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Heather J Ribaudo
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Steven K Grinspoon
- Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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13
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Sil S, Thangaraj A, Oladapo A, Hu G, Kutchy NA, Liao K, Buch S, Periyasamy P. Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging. Viruses 2022; 15:44. [PMID: 36680084 PMCID: PMC9866731 DOI: 10.3390/v15010044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/15/2022] [Accepted: 12/20/2022] [Indexed: 12/25/2022] Open
Abstract
Chronic low-grade inflammation remains an essential feature of HIV-1 infection under combined antiretroviral therapy (cART) and contributes to the accelerated cognitive defects and aging in HIV-1 infected populations, indicating cART limitations in suppressing viremia. Interestingly, ~50% of the HIV-1 infected population on cART that develops cognitive defects is complicated by drug abuse, involving the activation of cells in the central nervous system (CNS) and neurotoxin release, altogether leading to neuroinflammation. Neuroinflammation is the hallmark feature of many neurodegenerative disorders, including HIV-1-associated neurocognitive disorders (HAND). Impaired autophagy has been identified as one of the underlying mechanisms of HAND in treated HIV-1-infected people that also abuse drugs. Several lines of evidence suggest that autophagy regulates CNS cells' responses and maintains cellular hemostasis. The impairment of autophagy is associated with low-grade chronic inflammation and immune senescence, a known characteristic of pathological aging. Therefore, autophagy impairment due to CNS cells, such as neurons, microglia, astrocytes, and pericytes exposure to HIV-1/HIV-1 proteins, cART, and drug abuse could have combined toxicity, resulting in increased neuroinflammation, which ultimately leads to accelerated aging, referred to as neuroinflammaging. In this review, we focus on the potential role of autophagy in the mechanism of neuroinflammaging in the context of HIV-1 and drug abuse.
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Affiliation(s)
- Susmita Sil
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Annadurai Thangaraj
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Centre for Excellence in Nanobio Translational Research, Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India
| | - Abiola Oladapo
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Guoku Hu
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Naseer A Kutchy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA
| | - Ke Liao
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA 90048, USA
| | - Shilpa Buch
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Palsamy Periyasamy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
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14
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Ali MW, Ayanbisi I, Adamu S, Saad FK, Musa MS, Ayoola YA. Assessment of cardiovascular risk factors in obese women with HIV. Int J STD AIDS 2022; 33:1206-1211. [PMID: 36255193 DOI: 10.1177/09564624221132626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND The risk of significant weight gain/obesity associated with recently adopted antiretroviral therapy (ART) has been shown to be particularly higher among the black race, and female gender compared to their male counterparts. Herein, we evaluated and compared subclinical CVD risk between apparently healthy obese (BMI ≥30 kg/m2) and age matched normal BMI (BMI 18.5-24.9 kg/m2) women with HIV (WWH) on ART. METHODS This was a hospital-based cross-sectional study of adult (≥18 years) WWH. Conventional two-dimensional echocardiography and doppler imaging parameters, lipid profile, and high sensitivity C-reactive protein (hsCRP) measures were compared between the two groups. Multivariable regression analysis was done to determine independent variables. RESULT A total of 60 WWH were evaluated, 30 participants in each group. The mean age of the participants and duration on ART was 36.26 ± 5.71 and 10.23 ± 5.04 (years) respectively. Measured hsCRP, total cholesterol, and low-density lipoproteins were significantly (p = 0.002, p = 0.044, and p = 0.016 respectively) elevated in the obese group. Obese WWH had higher left atrial diameter, left atrial volume, left atrial area, aortic diameter, left ventricular mass (LVM), left ventricular mass index (LVMI), intraventricular septum in systole/diastole, left ventricular posterior wall in diastole and systole (p < 0.001, p = 0.018, p = 0.004, p = 0.025, p < 0.001, p = 0.019/p < 0.001, p = 0.020, and p = 0.021 respectively). On multivariable regression analysis, the measured serum biomarker hsCRP and the echocardiographic variables LVM and LVMI were independently associated (p = 0.02, p = 0.001 and p = 0.022 respectively) with BMI. CONCLUSION Obese WWH had higher biomarkers of CVDs and alterations in left ventricular structure that may increase their risk for adverse cardiovascular morbidity and mortality.
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Affiliation(s)
- Mohammed W Ali
- College of Medical Sciences, 475041Gombe State University, Gombe, Nigeria.,Department of Medicine, 291499Federal Teaching Hospital Gombe, Gombe, Nigeria
| | - Ismail Ayanbisi
- Department of Medicine, 291499Federal Teaching Hospital Gombe, Gombe, Nigeria
| | - Simon Adamu
- Department of Chemical Pathology, Federal Teaching Hospital Gombe, Gombe, Nigeria
| | - Fadimatu K Saad
- Department of Medicine, 291499Federal Teaching Hospital Gombe, Gombe, Nigeria
| | - Muhammad S Musa
- Department of Medicine, Yobe State University Teaching Hospital, Damaturu, Nigeria
| | - Yekeen A Ayoola
- College of Medical Sciences, 475041Gombe State University, Gombe, Nigeria.,Department of Medicine, 291499Federal Teaching Hospital Gombe, Gombe, Nigeria
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15
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Boczar KE, Faller E, Zeng W, Wang J, Small GR, Corrales-Medina VF, deKemp RA, Ward NC, Beanlands RSB, MacPherson P, Dwivedi G. Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study. J Nucl Cardiol 2022; 29:3057-3068. [PMID: 34820771 DOI: 10.1007/s12350-021-02830-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/22/2021] [Indexed: 01/29/2023]
Abstract
AIMS This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin. METHODS AND RESULTS Of the 35 HIV+ patients enrolled, 17 were randomized to treatment with 10 mg/day rosuvastatin and 18 to usual care for 6 months. An HIV- control cohort was selected for baseline comparison of serum inflammatory markers and monocyte markers of inflammation. 18F-FDG-PET/CT imaging of bone marrow, spleen, and thoracic aorta was performed in the HIV+ cohort at baseline and 6 months. While CD14++CD16- and CCR2 expressions were reduced, serum levels of IL-7, IL-8, and MCP-1 were elevated in the HIV+ population compared to the controls. There was a significant drop in FDG uptake in the bone marrow (TBRmax), spleen (SUVmax) and thoracic aortic (TBRmax) in the statin-treated group compared to the control group (bone marrow: - 10.3 ± 16.9% versus 5.0 ± 18.9%, p = .0262; spleen: - 9.8 ± 20.3% versus 11.3 ± 28.8%, p = .0497; thoracic aorta: - 19.1 ± 24.2% versus 4.3 ± 15.4%, p = .003). CONCLUSIONS HIV+ patients had significantly markers of systemic inflammation including monocyte activation. Treatment with low-dose rosuvastatin in the HIV+ cohort significantly reduced bone marrow, spleen and thoracic aortic FDG uptake.
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Affiliation(s)
- Kevin E Boczar
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Elliot Faller
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Wanzhen Zeng
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Jerry Wang
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Gary R Small
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Vicente F Corrales-Medina
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Robert A deKemp
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Natalie C Ward
- School of Public Health, Curtin University, Perth, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| | - Rob S B Beanlands
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Paul MacPherson
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Girish Dwivedi
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada.
- School of Medicine, University of Western Australia, Perth, Australia.
- Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, The University of Western Australia, Murdoch, Australia.
- Department of Cardiology, Fiona Stanley Hospital, Murdoch, WA, 6009, Australia.
- School of Biomedical Sciences at Curtin University, Perth, WA, Australia.
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16
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Kelly C, Gurung R, Kamng'ona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Heyderman R, Mallon P, Mwandumba H, Khoo S, Klein N. Circulating microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness: a nested case control study. Wellcome Open Res 2022; 6:264. [PMID: 36300175 PMCID: PMC9577278 DOI: 10.12688/wellcomeopenres.17044.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2022] [Indexed: 11/20/2022] Open
Abstract
Background: We aim to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with a new diagnosis of HIV and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) were carried out in a cohort of adults with a new HIV diagnosis and CD4 <100 cells/µL at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic BP and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% CI 4 - 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness [spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions: Circulating microparticles associate strongly with arterial stiffness among PLWH in Malawi. Endothelial and platelet microparticles are the predominant cell origin types, indicating that platelet driven endothelial dysfunction pathways warrant further investigation in HIV associated arterial stiffness.
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Affiliation(s)
- Christine Kelly
- Centre for Experimental Pathogen Host Research, UCD, Dublin, Ireland
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Rijan Gurung
- Institute of Infection, immunity and Inflammation, UCL, London, UK
| | - Raphael Kamng'ona
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Irene Sheha
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Mishek Chammudzi
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Kondwani Jambo
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Liverpool School of Tropical Medicine, LSTM, Liverpool, UK
| | - Jane Mallewa
- College of Medicine, University of Malawi, Blantyre, Malawi
| | - Alicja Rapala
- Institute of Cardiovascular Science, UCL, London, UK
| | - Rob Heyderman
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Institute of Infection, immunity and Inflammation, UCL, London, UK
| | - Patrick Mallon
- Centre for Experimental Pathogen Host Research, UCD, Dublin, Ireland
| | - Henry Mwandumba
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Liverpool School of Tropical Medicine, LSTM, Liverpool, UK
| | - Saye Khoo
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Nigel Klein
- Institute of Infection, immunity and Inflammation, UCL, London, UK
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17
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Wagle A, Goerlich E, Post WS, Woldu B, Wu KC, Hays AG. HIV and Global Cardiovascular Health. Curr Cardiol Rep 2022; 24:1149-1157. [PMID: 35802233 DOI: 10.1007/s11886-022-01741-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/19/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE OF REVIEW Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. RECENT FINDINGS PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.
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Affiliation(s)
- Anjali Wagle
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA
| | - Erin Goerlich
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA
| | - Wendy S Post
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA.,Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bethel Woldu
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA.,MedStar Heart and Vascular Institute, Baltimore, MD, USA.,Department of Medicine, Division of Cardiology, MedStar Georgetown University, Washington, DC, USA
| | - Katherine C Wu
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA.,Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Allison G Hays
- Department of Medicine, Johns Hopkins Division of Cardiology, Baltimore, MD, USA. .,Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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18
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Lewis JE, Poles J, Garretson E, Tiozzo E, Goldberg S, Campbell CSG, Simões HG, Woolger JM, Konefal J. Are Physical Fitness and CRP Related to Framingham Risk Score in HIV+ Adults? Am J Lifestyle Med 2022; 16:229-240. [DOI: 10.1177/1559827620904345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 01/15/2020] [Indexed: 11/15/2022] Open
Abstract
Background. People living with HIV (PLWH) have increased risk of cardiovascular disease (CVD). The Framingham Risk Score (FRS) predicts a 10-year CVD risk. Its relationships to physical fitness and C-reactive protein (CRP) are not well established. The current aim is to determine the links between FRS, physical fitness, and CRP in PLWH. Methods. Participants (n = 87) were assessed on multiple biomarkers. The FRS was calculated with the respective variables. Other variables that correlated significantly with FRS were entered into a regression equation to determine their relationship to FRS. Results. The FRS for men was more than twice that for women (12.8 vs 6.0, P < .001). Men were more fit than women, but most participants were not fit. Aerobic capacity was predictive of FRS in men, but not in women, and muscular strength was not predictive of FRS. Women had more than double the CRP compared with men (7.9 vs 3.5 mg/L, P < .01), and it was unrelated to FRS. Conclusions. In men, aerobic capacity was significantly predictive of FRS, but muscular strength and CRP were unrelated to FRS in both genders. These results do not conclusively demonstrate that physical fitness and CRP are related to FRS in PLWH.
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Affiliation(s)
- John E. Lewis
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Jillian Poles
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Eleanor Garretson
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Eduard Tiozzo
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Sharon Goldberg
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Carmen S. G. Campbell
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Herbert G. Simões
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Judi M. Woolger
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
| | - Janet Konefal
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida (JEL, EG, ET)
- Department of Kinesiology and Sport Sciences, University of Miami School of Education and Human Development, Miami, Florida (JP)
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico (SG)
- Catholic University of Brasilia, Brasilia, Brazil (CSGC, HGS)
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida (JMW)
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19
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Amador-Lara F, Andrade-Villanueva JF, Vega-Magaña N, Peña-Rodríguez M, Alvarez-Zavala M, Sanchez-Reyes K, Toscano-Piña M, Peregrina-Lucano AA, Del Toro-Arreola S, González-Hernández LA, Bueno-Topete MR. Gut microbiota from Mexican patients with metabolic syndrome and HIV infection: an inflammatory profile. J Appl Microbiol 2022; 132:3839-3852. [PMID: 35218591 DOI: 10.1111/jam.15505] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022]
Abstract
AIM A remarkable increase in metabolic syndrome (MetS) has occurred in HIV-infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore the profile of the gut microbiota in Mexican population with HIV infection and MetS. METHODS AND RESULTS Thirty HIV-infected patients with MetS compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next-generation sequencing. High sensitivity C-reactive protein >3mg l-1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α-diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short-chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus, and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS. CONCLUSIONS HIV-infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented. SIGNIFICANCE AND IMPACT OF STUDY Dysbiosis in MetS HIV-infected patients is a promising therapeutic target.
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Affiliation(s)
- Fernando Amador-Lara
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México.,Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Jaime F Andrade-Villanueva
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México.,Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Natali Vega-Magaña
- Laboratorio de Diagnóstico de Enfermedades Emergentes y Reemergentes (LaDEER), Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México.,Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México
| | - Marcela Peña-Rodríguez
- Instituto de Investigación en Enfermedades Crónico-Degenerativas (IECD), Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México
| | - Monserrat Alvarez-Zavala
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México.,Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Karina Sanchez-Reyes
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México.,Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Marcela Toscano-Piña
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Alejandro A Peregrina-Lucano
- Departamento de Farmacobiología; Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán #1421, esq. Olímpica, C.P. 44430, Guadalajara, Jalisco, México
| | - Susana Del Toro-Arreola
- Instituto de Investigación en Enfermedades Crónico-Degenerativas (IECD), Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México
| | - Luz A González-Hernández
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México.,Instituto de Investigación en Inmunodeficiencias y VIH (InIVIH), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Hospital #278, colonia el Retiro, CP 44280, Guadalajara, Jalisco, México
| | - Miriam R Bueno-Topete
- Instituto de Investigación en Enfermedades Crónico-Degenerativas (IECD), Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, CP 44340, Guadalajara, Jalisco, México
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20
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Hughey CM, Vuong BW, Ribaudo HB, Mitchell CCK, Korcarz CE, Hodis HN, Currier JS, Stein JH. Grayscale Ultrasound Texture Features of Carotid and Brachial Arteries in People With HIV Infection Before and After Antiretroviral Therapy. J Am Heart Assoc 2022; 11:e024142. [PMID: 35179037 PMCID: PMC9075086 DOI: 10.1161/jaha.121.024142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background We aimed to investigate novel grayscale ultrasound characteristics of the carotid and brachial arteries in people with HIV infection before and after starting initial antiretroviral therapy (ART). Methods and Results We performed grayscale ultrasound image analyses of the common carotid artery (CCA) and brachial artery before and after receipt of 1 of 3 randomly allocated ART regimens. We measured arterial wall echogenicity (grayscale median), contrast (gray-level difference statistic method), and entropy. These measures and their changes were compared with atherosclerotic cardiovascular disease risk factors, measures of HIV disease severity, and inflammatory biomarkers before and after ART. Changes in the grayscale measures were evaluated within and between ART arms. Among 201 ART-naïve people with HIV, higher systolic blood pressure, higher body mass index, lower CD4+ T cells, and non-Hispanic White race and ethnicity were associated independently with lower CCA grayscale median. Changes in each CCA grayscale measure from baseline to 144 weeks correlated with changes in soluble CD163: grayscale median (ρ=-0.17; P=0.044), gray-level difference statistic-contrast (ρ=-0.19; P=0.024), and entropy (ρ=-0.21; P=0.016). Within the atazanavir/ritonavir arm, CCA entropy increased (adjusted β=0.023 [95% CI, 0.001-0.045]; P=0.04), but no other within-arm changes in grayscale measures were seen. Correlations of brachial artery grayscale measures were weaker. Conclusions In ART-naïve people with HIV, CCA grayscale ultrasound measures were associated with atherosclerotic cardiovascular disease risk factors and lower grayscale median was associated with lower CD4+ T cells. Reductions in soluble CD163 with initial ART were associated with improvements in all 3 CCA grayscale measures, suggesting that reductions in macrophage activation with ART initiation may lead to less arterial injury. Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT00811954; NCT00851799.
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Affiliation(s)
| | - Belinda W Vuong
- University of Wisconsin School of Medicine and Public Health Madison WI
| | | | | | - Claudia E Korcarz
- University of Wisconsin School of Medicine and Public Health Madison WI
| | - Howard N Hodis
- Keck School of Medicine of University of Southern California Los Angeles CA
| | - Judith S Currier
- David Geffen School of Medicine at University of California-Los Angeles Los Angeles CA
| | - James H Stein
- University of Wisconsin School of Medicine and Public Health Madison WI
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21
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Derry HM, Johnston CD, Burchett CO, Brennan-Ing M, Karpiak S, Zhu YS, Siegler EL, Glesby MJ. Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV. J Gerontol B Psychol Sci Soc Sci 2022; 77:50-60. [PMID: 33580236 PMCID: PMC8755907 DOI: 10.1093/geronb/gbab027] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years. METHOD Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (β = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (β = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (β = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers. DISCUSSION Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.
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Affiliation(s)
- Heather M Derry
- Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, US
| | - Carrie D Johnston
- Division of Infectious Diseases, Weill Cornell Medicine, New York, US
| | - Chelsie O Burchett
- Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, US
- Department of Psychology, Stony Brook University, New York, US
| | - Mark Brennan-Ing
- Brookdale Center for Healthy Aging, Hunter College, City University of New York, US
| | - Stephen Karpiak
- ACRIA Center on HIV & Aging at GMHC, New York, US
- New York University, Rory Meyers College of Nursing, US
| | - Yuan-Shan Zhu
- Department of Medicine and Clinical and Translational Science Center, Weill Cornell Medicine, New York, US
| | - Eugenia L Siegler
- Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, US
| | - Marshall J Glesby
- Division of Infectious Diseases, Weill Cornell Medicine, New York, US
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22
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Kelly C, Gurung R, Kamng'ona R, Sheha I, Chammudzi M, Jambo K, Mallewa J, Rapala A, Heyderman R, Mallon P, Mwandumba H, Khoo S, Klein N. Circulating microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness: a nested case control study. Wellcome Open Res 2021; 6:264. [PMID: 36300175 PMCID: PMC9577278 DOI: 10.12688/wellcomeopenres.17044.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2021] [Indexed: 03/21/2024] Open
Abstract
Background: We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Antiretroviral therapy (ART)-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic blood pressure (BP) and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% confidence interval [CI] 4 - 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness (spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions: Circulating microparticles associate strongly with arterial stiffness among people living with HIV in Malawi. Endothelial damage and platelet microparticles are the predominant cell origin types and future translational studies could consider prioritising these pathways.
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Affiliation(s)
- Christine Kelly
- Centre for Experimental Pathogen Host Research, UCD, Dublin, Ireland
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Rijan Gurung
- Institute of Infection, immunity and Inflammation, UCL, London, UK
| | - Raphael Kamng'ona
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Irene Sheha
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Mishek Chammudzi
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
| | - Kondwani Jambo
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Liverpool School of Tropical Medicine, LSTM, Liverpool, UK
| | - Jane Mallewa
- College of Medicine, University of Malawi, Blantyre, Malawi
| | - Alicja Rapala
- Institute of Cardiovascular Science, UCL, London, UK
| | - Rob Heyderman
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Institute of Infection, immunity and Inflammation, UCL, London, UK
| | - Patrick Mallon
- Centre for Experimental Pathogen Host Research, UCD, Dublin, Ireland
| | - Henry Mwandumba
- Malawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, Malawi, Malawi
- Liverpool School of Tropical Medicine, LSTM, Liverpool, UK
| | - Saye Khoo
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Nigel Klein
- Institute of Infection, immunity and Inflammation, UCL, London, UK
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23
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Hameiri-Bowen D, Sovershaeva E, Flaegstad T, Gutteberg TJ, Ngwira LG, Simms V, Rehman AM, Mchugh G, Bandason T, Ferrand RA, Rowland-Jones S, Yindom LM. Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection. AIDS 2021; 35:1743-1751. [PMID: 34074817 PMCID: PMC7611698 DOI: 10.1097/qad.0000000000002964] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVE HIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD. DESIGN Case--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility. METHODS Cryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD. RESULTS Biomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association. CONCLUSION HCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.
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Affiliation(s)
- Dan Hameiri-Bowen
- University of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom
| | - Evgeniya Sovershaeva
- UiT The Arctic University of Norway
- University Hospital of North Norway, Tromsø, Norway
| | - Trond Flaegstad
- UiT The Arctic University of Norway
- University Hospital of North Norway, Tromsø, Norway
| | - Tore Jarl Gutteberg
- UiT The Arctic University of Norway
- University Hospital of North Norway, Tromsø, Norway
| | - Lucky Gift Ngwira
- Liverpool School of Tropical Medicine, Liverpool, UK
- Malawi-Liverpool Wellcome Trust Clinical Research Program, Blantyre, Malawi
| | - Victoria Simms
- International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Andrea M Rehman
- International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Grace Mchugh
- Department of Clinical Research
- Biomedical Research and Training Institute, Harare, Zimbabwe
| | - Tsitsi Bandason
- Biomedical Research and Training Institute, Harare, Zimbabwe
| | - Rashida Abbas Ferrand
- Department of Clinical Research
- Biomedical Research and Training Institute, Harare, Zimbabwe
| | - Sarah Rowland-Jones
- University of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom
| | - Louis-Marie Yindom
- University of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom
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24
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Achhra AC, Lyass A, Borowsky L, Bogorodskaya M, Plutzky J, Massaro JM, D'Agostino RB, Triant VA. Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations. Curr HIV/AIDS Rep 2021; 18:271-279. [PMID: 34247329 PMCID: PMC8733948 DOI: 10.1007/s11904-021-00567-w] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). RECENT FINDINGS Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians' ability to deliver optimal preventive care.
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Affiliation(s)
- Amit C Achhra
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Asya Lyass
- Department of Mathematics and Statistics, Boston University, Boston, MA, USA
| | - Leila Borowsky
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Milana Bogorodskaya
- Division of Infectious Diseases, MetroHealth, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jorge Plutzky
- Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA
| | - Joseph M Massaro
- Department of Mathematics and Statistics, Boston University, Boston, MA, USA
| | - Ralph B D'Agostino
- Department of Mathematics and Statistics, Boston University, Boston, MA, USA
| | - Virginia A Triant
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 02114, USA.
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
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25
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Mueller MC, Usadel S, Kern WV, Zirlik A, Zhou Q. Proportion of patients eligible for statin therapy substantially varies between different cardiovascular disease risk calculators and guidelines used. Int J STD AIDS 2021; 32:1188-1195. [PMID: 34233537 DOI: 10.1177/09564624211029392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Because people living with HIV (PLWH) have an elevated risk for cardiovascular disease (CVD), prevention of CVD should be integrated in to HIV care. In this study, we compared the agreement between three risk scores and evaluated the indication for statin therapy based on guidelines of the American Heart Association and European AIDS Clinical Society. This study is a cross-sectional, single-center study. All PLWH ≥ 30 years without CVD and statin therapy were consecutively enrolled. Agreement between CVD risk estimates was assessed using Cohen's kappa coefficient. Of 488 PLWH, 41.2% were female with a median age of 47.8 years. D:A:D-R classified the highest proportion of patients in the categories of high/very high risk for CVD (17.8%) compared to SCORE (4.7%) and FRS (13.7%). D:A:D-R and SCORE (κ = 0.11) as well as D:A:D-R and FRS (κ = 0.33) showed poor agreement. Based on different CVD risk equations and guidelines, indication for statin therapy ranged from 34.8% to 92.0% of patients. In conclusion, a high proportion of PLWH is at high risk for CVD likely underestimated by treating physicians. Inconsistencies in the evaluation of CVD risk and primary prophylaxis should be tackled by an interdisciplinary approach.
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Affiliation(s)
- Matthias C Mueller
- Division of Infectious Diseases, Department of Medicine II, Medical Center, Faculty of Medicine, 9174University of Freiburg, Freiburg, Germany.,Department of Infection Medicine, Medical Care Center, MVZ Clotten, Freiburg, Germany
| | - Susanne Usadel
- Department of Infection Medicine, Medical Care Center, MVZ Clotten, Freiburg, Germany
| | - Winfried V Kern
- Division of Infectious Diseases, Department of Medicine II, Medical Center, Faculty of Medicine, 9174University of Freiburg, Freiburg, Germany
| | - Andreas Zirlik
- Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, 9174University of Freiburg, Freiburg, Germany.,Division of Cardiology, 31475Medical University of Graz, Graz, Austria
| | - Qian Zhou
- Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, 9174University of Freiburg, Freiburg, Germany.,Department of Cardiology, 30262University Hospital of Basel, Basel, Switzerland
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26
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Patel AA, Budoff MJ. Coronary Artery Disease in Patients with HIV Infection: An Update. Am J Cardiovasc Drugs 2021; 21:411-417. [PMID: 33184766 DOI: 10.1007/s40256-020-00451-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/30/2020] [Indexed: 12/13/2022]
Abstract
Premature cardiovascular disease among the HIV-infected population is of great concern among clinicians. The increased life expectancy of HIV-infected individuals is mainly due to the early detection of infection and the advent of antiretroviral therapy. Once known as a deadly disease, HIV infection has transitioned into a chronic condition. Cardiovascular disease in this population is thought to progress early due to traditional and non-traditional risk factors. Early detection of subclinical atherosclerosis has become a center of focus in research as our complete understanding of this process it not yet well known. Advancements in cardiac computed tomography angiography has enabled the exploration of coronary artery disease by further evaluation of coronary stenosis and plaque analysis. An increase in cardiovascular event rates in this population is currently thought to be linked to antiretroviral therapy, Framingham risk factors, and HIV. We sought to present an updated comprehensive review of the available literature on HIV related to atherosclerosis and cardiovascular risk.
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Affiliation(s)
- Amish A Patel
- Division of Cardiology, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA
- Division of Cardiology, University of California Riverside School of Medicine, Riverside, CA, USA
| | - Matthew J Budoff
- Division of Cardiology, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
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27
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Triant VA, Gandhi RT. When Epidemics Collide: Why People With Human Immunodeficiency Virus May Have Worse Coronavirus Disease 2019 Outcomes and Implications for Vaccination. Clin Infect Dis 2021; 72:e1030-e1034. [PMID: 33395474 PMCID: PMC7799344 DOI: 10.1093/cid/ciaa1946] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Indexed: 12/13/2022] Open
Affiliation(s)
- Virginia A Triant
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Rajesh T Gandhi
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
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28
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Testosterone, HIV, and cardiovascular disease risk. Cardiovasc Endocrinol Metab 2021; 10:72-79. [PMID: 34124602 PMCID: PMC8189608 DOI: 10.1097/xce.0000000000000236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 09/04/2020] [Indexed: 11/26/2022]
Abstract
There has been a recent increase in the use of testosterone supplementation among young adults in the United States, despite the controversy of testosterone replacement therapy (TRT) and cardiovascular safety. The lower testosterone levels and earlier age of TRT use in persons living with HIV (PLHIV) is of particular relevance for this population because cardiovascular disease (CVD) comorbidities are known to be increased among PLHIV. There is very limited data on TRT in PLHIV, as such, in this article, we sought to compile current evidence regarding the diagnosis and management of testosterone deficiency and its link to CVD risk including among PLHIV.
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29
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Siedner MJ, Bibangambah P, Kim J, Lankowski A, Chang JL, Yang IT, Kwon DS, North CM, Triant VA, Longenecker C, Ghoshhajra B, Peck RN, Sentongo RN, Gilbert R, Kakuhikire B, Boum Y, Haberer JE, Martin JN, Tracy R, Hunt PW, Bangsberg DR, Tsai AC, Hemphill LC, Okello S. Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study. J Am Heart Assoc 2021; 10:e019994. [PMID: 34096320 PMCID: PMC8477876 DOI: 10.1161/jaha.120.019994] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.
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Affiliation(s)
- Mark J. Siedner
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
| | - Prossy Bibangambah
- Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
| | - June‐Ho Kim
- Department of MedicineHarvard Medical SchoolBostonMA,Department of MedicineBrigham and Women's HospitalBostonMA
| | - Alexander Lankowski
- Department of MedicineUniversity of WashingtonSeattleWA,Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research CenterSeattleWA
| | - Jonathan L. Chang
- Department of MedicineHarvard Medical SchoolBostonMA,Department of MedicineBrigham and Women's HospitalBostonMA
| | - Isabelle T. Yang
- Department of MedicineGeisel School of Medicine at DartmouthHanoverNH
| | - Douglas S. Kwon
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and HarvardCambridgeMA
| | - Crystal M. North
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | - Virginia A. Triant
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | | | - Brian Ghoshhajra
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | - Robert N. Peck
- Center for Global HealthWeill Cornell Medical CollegeNew YorkNY
| | - Ruth N. Sentongo
- Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
| | - Rebecca Gilbert
- Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | - Bernard Kakuhikire
- Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
| | - Yap Boum
- Epicentre Research BaseMbararaUganda
| | - Jessica E. Haberer
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | | | - Russell Tracy
- Department of Pathology and Laboratory MedicineUniversity of VermontBurlingtonVT
| | - Peter W. Hunt
- Department of MedicineUniversity of CaliforniaSan FranciscoCA
| | | | - Alexander C. Tsai
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
| | - Linda C. Hemphill
- Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
| | - Samson Okello
- Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
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30
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Jan AK, Moore JV, Wang RJ, Mcging M, Farr CK, Moisi D, Hartman-Filson M, Kerruish R, Jeon D, Lewis E, Crothers K, Lederman MM, Hunt PW, Huang L. Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV. AIDS 2021; 35:1031-1040. [PMID: 33635847 PMCID: PMC8102352 DOI: 10.1097/qad.0000000000002846] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco). DESIGN Cross-sectional, observational study. METHODS Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression. RESULTS Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco. CONCLUSION Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.
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Affiliation(s)
- Amanda K Jan
- Division of HIV, Infectious Diseases and Global Medicine
| | - Julia V Moore
- Division of HIV, Infectious Diseases and Global Medicine
| | - Richard J Wang
- Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
| | - Maggie Mcging
- Division of HIV, Infectious Diseases and Global Medicine
| | - Carly K Farr
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA
| | - Daniela Moisi
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH
| | | | - Robert Kerruish
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA
| | - Diane Jeon
- Division of HIV, Infectious Diseases and Global Medicine
| | - Eula Lewis
- Department of Anesthesia and Perioperative Care, San Francisco General Hospital
| | - Kristina Crothers
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA
| | - Michael M Lederman
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH
| | - Peter W Hunt
- Division of Experimental Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA
| | - Laurence Huang
- Division of HIV, Infectious Diseases and Global Medicine
- Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
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31
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Hoffmann U, Lu MT, Foldyna B, Zanni MV, Karady J, Taron J, Zhai BK, Burdo T, Fitch KV, Kileel EM, Williams K, Fichtenbaum CJ, Overton ET, Malvestutto C, Aberg J, Currier J, Sponseller CA, Melbourne K, Floris-Moore M, Van Dam C, Keefer MC, Koletar SL, Douglas PS, Ribaudo H, Mayrhofer T, Grinspoon SK. Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention. JAMA Netw Open 2021; 4:e2114923. [PMID: 34185068 PMCID: PMC8243232 DOI: 10.1001/jamanetworkopen.2021.14923] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
IMPORTANCE Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. OBJECTIVES To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. DESIGN, SETTING, AND PARTICIPANTS This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. EXPOSURE HIV disease. MAIN OUTCOMES AND MEASURES The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). RESULTS The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). CONCLUSIONS AND RELEVANCE In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.
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Affiliation(s)
| | | | | | | | - Julia Karady
- Massachusetts General Hospital, Boston
- MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Jana Taron
- Massachusetts General Hospital, Boston
- University Hospital Freiburg, Freiburg, Germany
| | - Bingxue K. Zhai
- Massachusetts General Hospital, Boston
- Brigham and Women’s Hospital, Boston, Massachusetts
| | | | | | | | | | | | | | | | - Judith Aberg
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | | | | | - Cornelius Van Dam
- Greensboro Clinical Research Site, Cone Health, Greensboro, North Carolina
| | - Michael C. Keefer
- University of Rochester Adult HIV Therapeutic Strategies Network Clinical Research Site, Rochester, New York
| | | | - Pamela S. Douglas
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
| | - Heather Ribaudo
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Thomas Mayrhofer
- Massachusetts General Hospital, Boston
- School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
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32
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Wiebe SA, Balfour L, Cameron WD, Sandre D, Holly C, Tasca GA, MacPherson PA. Psychological changes in successful completers of an HIV-tailored smoking cessation program: mood, attachment and self-efficacy. AIDS Care 2021; 34:689-697. [PMID: 33880980 DOI: 10.1080/09540121.2021.1909697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
High rates of cigarette smoking is the leading contributor to the increasing risk of cardiovascular disease (CVD) among people living with HIV (PLH). Relapse rates among PLH who quit smoking are high among those receiving standard care, which may be due to several unique social and psychological challenges PLH face when they attempt to quit smoking. The purpose of the current study was to examine change in relevant psychological factors in a subgroup of participants (n = 14) who remained smoke-free at 6-months follow-up in an HIV-tailored smoking cessation counselling program (N = 50). We examined self-reported depressive symptoms, attachment style and self-efficacy across 5 time points (baseline, quite date, 4, 12 and 24 weeks). At study baseline, mean depression scores fell above the clinical cut off of 16 (M = 16.31; SD = 13.53) on the Centre for Epidemiological Studies - Depression (CES-D) scale and fell below the clinical cut off at 24 weeks post quit date (M = 13.36; SD = 10.62). Results of multi-level modeling indicated a significant linear reduction in depressive symptoms and a significant linear improvement in self-efficacy to refrain from smoking across study visits. These results suggest that positive change in mood and self-efficacy may be helpful for PLH who remain smoke-free during a quit attempt.
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Affiliation(s)
- Stephanie A Wiebe
- Department of Psychology, The Ottawa Hospital, Ottawa, Canada.,School of Psychology, University of Ottawa, Ottawa, Canada
| | - Louise Balfour
- Department of Psychology, The Ottawa Hospital, Ottawa, Canada.,Department of Medicine, University of Ottawa, Ottawa, Canada.,Ottawa Hospital Research Institute, Ottawa, Canada
| | - William D Cameron
- Ottawa Hospital Research Institute, Ottawa, Canada.,Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada.,Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Daniella Sandre
- Department of Psychology, The Ottawa Hospital, Ottawa, Canada.,Ottawa Hospital Research Institute, Ottawa, Canada.,Department of Psychology, University of Ottawa, Ottawa, Canada
| | - Crystal Holly
- Department of Psychology, The Ottawa Hospital, Ottawa, Canada.,Ottawa Hospital Research Institute, Ottawa, Canada
| | | | - Paul A MacPherson
- Ottawa Hospital Research Institute, Ottawa, Canada.,Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada.,Faculty of Medicine, University of Ottawa, Ottawa, Canada
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Boldeanu I, Sadouni M, Mansour S, Baril JG, Trottier B, Soulez G, S Chin A, Leipsic J, Tremblay C, Durand M, Chartrand-Lefebvre C. Prevalence and Characterization of Subclinical Coronary Atherosclerotic Plaque with CT among Individuals with HIV: Results from the Canadian HIV and Aging Cohort Study. Radiology 2021; 299:571-580. [PMID: 33876969 DOI: 10.1148/radiol.2021203297] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography (n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors. Results There were 181 PLWH (mean age, 56 years ± 7; 167 men) and 84 healthy volunteers (mean age, 57 years ± 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively; P = .45), as were CAC score (odds ratio [OR], 1.06; 95% CI: 0.58, 1.94; P = .85) and overall plaque prevalence (prevalence ratio, 1.07; 95% CI: 0.86, 1.32; P = .55) after adjustment for cardiovascular risk. Noncalcified plaque prevalence (prevalence ratio, 2.5; 95% CI: 1.07, 5.67; P = .03) and volume (OR, 2.8; 95% CI: 1.05, 7.40; P = .04) were higher in PLWH. Calcified plaque frequency was reduced in PLWH (OR, 0.6; 95% CI: 0.40, 0.91; P = .02). Treatment with protease inhibitors was associated with higher volume of overall (OR, 1.8; 95% CI: 1.09, 2.85; P = .02) and mixed plaque (OR, 1.6; 95% CI: 1.04, 2.45; P = .03). Conclusion Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in asymptomatic people living with HIV without known cardiovascular disease compared with healthy volunteers without HIV. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lai in this issue.
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Affiliation(s)
- Irina Boldeanu
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Manel Sadouni
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Samer Mansour
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Jean-Guy Baril
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Benoît Trottier
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Gilles Soulez
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Anne S Chin
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Jonathon Leipsic
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Cécile Tremblay
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Madeleine Durand
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
| | - Carl Chartrand-Lefebvre
- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
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- From the Departments of Radiology (I.B., M.S., G.S., A.S.C., C.C.L.), Cardiology (S.M.), Family Medicine (J.G.B., B.T.), Microbiology (C.T.) and Internal Medicine (M.D.), University of Montreal Hospital (CHUM), 1051 Sanguinet St, Montréal, QC, Canada H2X 0C1; and Department of Radiology, Providence Health Care, Vancouver, Canada (J.L.). Members of the Canadian HIV and Aging Cohort Study Group are listed in the acknowledgments
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Bares SH, Smeaton LM, Scott SE, Smith BA, Godfrey C, McComsey GA. The Association Between Weight Gain, Sex and Immune Activation Following the Initiation of Antiretroviral Therapy. J Infect Dis 2021; 224:1765-1774. [PMID: 33870433 DOI: 10.1093/infdis/jiab210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 04/16/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Immune activation persists despite suppressive antiretroviral therapy (ART) and may be affected by sex or body composition. We explored these relationships in a subset of participants who initiated ART in two large randomized trials. METHODS Purposeful sampling selected participants who achieved virologic suppression on ART and either maintained weight within +/- 0.5 kg/m 2 or gained 2.6-6.4 kg/m 2 from baseline to 96 weeks. We measured 7 markers of inflammation and immune activation at weeks 0 and 96. Multivariable linear regression explored associations of weight gain, sex, and pre-ART BMI with pre-ART and changes in biomarker concentrations. RESULTS 340 participants were selected; median pre-ART age 42 years, CD4+ cell count 273 cells/mm 3, HIV-1 RNA 4.7 log10 copies/mL; 49% were women, 33% white, 42% black, and 24% Hispanic. Among participants with a normal pre-ART BMI, higher pre-ART levels of IL-6, sTNF-RI and RII, CXCL-10, sCD163 and hsCRP were associated with weight gain. Association of weight gain with week 96 changes of these biomarkers differed by sex; women who gained weight had smaller declines in most measured biomarkers compared to men who gained. CONCLUSIONS Among women, weight gain is associated with attenuated decline in several immune activation markers following ART initiation.
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Affiliation(s)
- Sara H Bares
- University of Nebraska Medical Center, Omaha, NE, U.S
| | | | - Sarah E Scott
- University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, U.S
| | - Beth A Smith
- University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, U.S
| | - Catherine Godfrey
- Office of the Global AIDS Coordinator, Department of State, Washington D.C., U.S
| | - Grace A McComsey
- University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, U.S
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Rogers BG, Glynn TR, Bainter SA, McCauley T, Antoni MH, Safren SA. Syndemics and salivary inflammation in people living with HIV/AIDS. Psychol Health 2021; 36:496-510. [PMID: 32400209 PMCID: PMC7665986 DOI: 10.1080/08870446.2020.1763995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 04/21/2020] [Accepted: 04/24/2020] [Indexed: 10/24/2022]
Abstract
OBJECTIVE People living with HIV/AIDS (PLWHA) are disproportionally exposed to a host of structural, community, and individual-level physical and psychosocial stressors also termed 'syndemic conditions.' The current study aimed to examine the association between experiencing syndemic conditions and physiological stress response and be associated with bodily inflammation, including Interlekin-6 (IL-6) and C-reactive protein (CRP) in PLWHA. DESIGN Participants (N = 103) were recruited from a public HIV clinic. They provided saliva samples of IL-6 and CRP and completed psychosocial measures. MAIN OUTCOME MEASURES Levels of circulating salivary IL-6 and CRP. RESULTS When predictors (birth country, recent housing instability, and incarceration history) were simultaneously entered into a regression model, only incarceration history was negatively associated with IL-6 [b = -.27, t(98) = -3.11, p = .002]. For CRP, the resulting regression model was not significant, [F(3, 98) = 2.23, p = .090]. CONCLUSION Although we had expected higher levels of syndemics to be associated with higher levels of circulating inflammation, in our sample, length of incarceration was associated with lower levels of circulating IL-6. Findings are therefore suggestive of a stress response disruption resulting in a negative feedback loop as the long-term impact of chronic stress on inflammation.
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Affiliation(s)
- Brooke G. Rogers
- Department of Psychology, University of Miami, Coral Gables, FL, USA
| | - Tiffany R. Glynn
- Department of Psychology, University of Miami, Coral Gables, FL, USA
| | - Sierra A. Bainter
- Department of Psychology, University of Miami, Coral Gables, FL, USA
| | - Thomas McCauley
- Department of Psychology, University of Miami, Coral Gables, FL, USA
| | - Michael H. Antoni
- Department of Psychology, University of Miami, Coral Gables, FL, USA
| | - Steven A. Safren
- Department of Psychology, University of Miami, Coral Gables, FL, USA
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Ebner B, Vincent L, Grant J, Martinez C. Cardiac Catheterization Procedures in Patients with HIV: A Retrospective Analysis. J Cardiovasc Dev Dis 2021; 8:jcdd8040033. [PMID: 33801600 PMCID: PMC8066790 DOI: 10.3390/jcdd8040033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/24/2021] [Accepted: 03/24/2021] [Indexed: 11/29/2022] Open
Abstract
With the advent of effective antiretroviral therapies, there has been a decrease in HIV-related mortality, but an increase in non-AIDS-related comorbidities including cardiovascular disease (CVD). We sought to investigate current status of cardiac catheterization (CC) procedures in people with HIV (PWH). This is a retrospective study done at a University Hospital in South Florida between 2017 and 2019. Medical records from 985 PWH indicated that CC was performed in 1.9% of the cases. Of the PWH who underwent CC, 68% were found to have obstructive coronary artery disease (CAD). Among obstructive CAD cases, PCI was performed in 77% and CABG in 21% of cases; 26% had a repeat procedure and 11% died from non-cardiac causes. When comparing PWH who had CC to those who did not, there was a significantly higher rate of statin use (63% vs. 25%, p < 0.015) and a higher prevalence of low ejection fraction (38% vs. 11%, p = 0.004) among those patients who underwent CC. However, there was no significant difference in the prevalence of hypertension (p = 0.13), HbA1c levels (p = 0.32), CD4 count (p = 0.45) nor in undetectable viral load status (p = 0.75) after controlling for age, sex and BMI. Despite the finding of traditional CVD risk factors among PWH, there were no differences in HIV-related factors among patients requiring CC, supporting the importance of optimization of traditional CVD risk factors in this population.
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Affiliation(s)
- Bertrand Ebner
- Department of Internal Medicine, Jackson Health System/University of Miami Miller School of Medicine, Miami, FL 33136, USA; (L.V.); (J.G.)
- Correspondence: ; Tel.: +1-(305)-585-5400
| | - Louis Vincent
- Department of Internal Medicine, Jackson Health System/University of Miami Miller School of Medicine, Miami, FL 33136, USA; (L.V.); (J.G.)
| | - Jelani Grant
- Department of Internal Medicine, Jackson Health System/University of Miami Miller School of Medicine, Miami, FL 33136, USA; (L.V.); (J.G.)
| | - Claudia Martinez
- Department of Cardiovascular Disease, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
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Echocardiographic Findings Among Virally Suppressed HIV-Infected Aging Asians Compared with HIV-Negative Individuals. J Acquir Immune Defic Syndr 2021; 85:379-386. [PMID: 32701821 DOI: 10.1097/qai.0000000000002456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia. DESIGN A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand. METHODS All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors. RESULTS The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m were associated with pulmonary hypertension (P < 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities. CONCLUSIONS In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.
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Abstract
PURPOSE OF REVIEW Systemic inflammation increases as a consequence of aging (inflammaging) and contributes to age-related morbidities. Inflammation in people living with HIV is elevated compared with the general population even after prolonged suppression of viremia with anti-retroviral therapy. Mechanisms that contribute to inflammation during aging and in treated HIV disease are potentially interactive, leading to an exaggerated inflammatory phenotype in people with HIV. RECENT FINDINGS Recent studies highlight roles for anti-retroviral therapy, co-infections, immune system alterations, and microbiome perturbations as important contributors to HIV-associated inflammation. These factors likely contribute to increased risk of age-related morbidities in people living with HIV. Understanding mechanisms that exaggerate the inflammaging process in people with HIV may lead to improved intervention strategies, ultimately, extending both lifespan and healthspan.
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Cornwell A, Palli R, Singh MV, Benoodt L, Tyrell A, Abe JI, Schifitto G, Maggirwar SB, Thakar J. Molecular characterization of atherosclerosis in HIV positive persons. Sci Rep 2021; 11:3232. [PMID: 33547350 PMCID: PMC7865026 DOI: 10.1038/s41598-021-82429-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 12/30/2020] [Indexed: 01/30/2023] Open
Abstract
People living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.
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Affiliation(s)
- Adam Cornwell
- Department of Biomedical Genetics, University of Rochester, Rochester, NY, USA
| | - Rohith Palli
- Medical Scientist Training Program, University of Rochester, Rochester, NY, USA
- Biophysics, Structural, and Computational Biology PhD Program, University of Rochester, Rochester, NY, USA
| | - Meera V Singh
- Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA
| | - Lauren Benoodt
- Biophysics, Structural, and Computational Biology PhD Program, University of Rochester, Rochester, NY, USA
| | - Alicia Tyrell
- Department of Neurology, General Neurology, University of Rochester, Rochester, NY, USA
- Department of Imaging Sciences, University of Rochester, Rochester, NY, USA
| | - Jun-Ichi Abe
- Department of Cardiology-Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Texas A&M Health Science Center Institute of Biosciences and Technology, Houston, TX, USA
| | - Giovanni Schifitto
- Department of Neurology, General Neurology, University of Rochester, Rochester, NY, USA
- Department of Imaging Sciences, University of Rochester, Rochester, NY, USA
| | - Sanjay B Maggirwar
- Department of Microbiology, Immunology, and Tropical Medicine, George Washing University, Washington, DC, USA
| | - Juilee Thakar
- Department of Biomedical Genetics, University of Rochester, Rochester, NY, USA.
- Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
- Department of Biostatistics and Computational Biology, University of Rochester, 601 Elmwood Avenue, , Box 672, Rochester, NY, 14642, USA.
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Ghosn J, Abdoul H, Fellahi S, Merlet A, Salmon D, Morini JP, Deleuze J, Blacher J, Capeau J, Bastard JP, Viard JP. Prevalence of Silent Atherosclerosis and Other Comorbidities in an Outpatient Cohort of Adults Living with HIV: Associations with HIV Parameters and Biomarkers. AIDS Res Hum Retroviruses 2021; 37:101-108. [PMID: 33076677 DOI: 10.1089/aid.2020.0182] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
People living with HIV (PLWH) are at risk of noninfectious comorbidities. It is important to individualize those at higher risk. In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined by using Chi-square or Fisher's exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Among 790 participants [median age: 49.8 years (interquartile range, IQR: 44.5-55.6), 77.1% males, median CD4: 536/mm3 (IQR: 390-754), 83.6% with undetectable viral load], asymptomatic atherosclerosis was found in 26% and was associated in multivariate analysis with older age, longer known duration of infection, higher sCD14, and lower adiponectin levels. Hypertension was found in 33.5% of participants, diabetes in 19.4%, renal impairment in 14.6%, elevated low-density lipoprotein-cholesterol in 13.3%, elevated triglyceride/high-density lipoprotein (HDL)-cholesterol ratio in 6.6%, and osteoporosis in 7.9%. The presence of two or more comorbidities was found in 42.1% of participants and was associated in multivariate analysis with older age and longer exposure to antiretrovirals. Comorbidities were diversely associated with biomarkers: osteoporosis with higher IL-6, renal impairment with higher sCD14, hypertension with higher D-dimer, diabetes and elevated triglyceride/HDL-cholesterol ratio both with lower adiponectin and lower 25-hydroxyvitamin D. Asymptomatic atherosclerosis and multimorbidity were frequent in a cohort of middle-aged, well-controlled, PLWH and were associated with traditional and HIV-specific factors. Associations between morbidities and inflammatory/immune activation biomarkers were diverse.
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Affiliation(s)
- Jade Ghosn
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Hendy Abdoul
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Soraya Fellahi
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Audrey Merlet
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Dominique Salmon
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jean-Pierre Morini
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jean Deleuze
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jacques Blacher
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jacqueline Capeau
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jean-Philippe Bastard
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
| | - Jean-Paul Viard
- Immunology-Infectious Diseases Unit, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Centre-Université de Paris, Paris, France
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Kuk M, Ward NC, Dwivedi G. Extrinsic and Intrinsic Responses in the Development and Progression of Atherosclerosis. Heart Lung Circ 2021; 30:807-816. [PMID: 33468387 DOI: 10.1016/j.hlc.2020.12.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 11/25/2022]
Abstract
Atherosclerosis is a multifactorial disease that is thought to be primarily inflammatory in origin. Given the contribution of inflammation to the development and progression of atherosclerosis, other conditions that are characterised by a dysregulated inflammatory response have also been proposed to play a role. The purpose of this review is to organise and present the various inflammatory processes that can affect atherosclerosis into two broad categories: extrinsic or host-independent and intrinsic or host-dependent. Within these two categories, we will discuss various processes that may contribute to the development and progression of atherosclerosis and the clinical studies describing these associations. Although the clinical trials investigating anti-inflammatory therapies have to date provided mixed results, further studies, particularly in conjunction with lipid-lowering and blood pressure lowering therapies should be considered.
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Affiliation(s)
- Mariya Kuk
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada; McGill University Health Centre, McGill University, Montreal, Canada
| | - Natalie C Ward
- School of Public Health, Curtin University, Perth, WA, Australia; Medical School, University of Western Australia, Perth, WA, Australia
| | - Girish Dwivedi
- Medical School, University of Western Australia, Perth, WA, Australia; Harry Perkins Institute for Medical Research, Fiona Stanley Hospital, Perth, WA, Australia.
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Stein JH, Kime N, Korcarz CE, Ribaudo H, Currier JS, Delaney JC. Effects of HIV Infection on Arterial Endothelial Function: Results From a Large Pooled Cohort Analysis. Arterioscler Thromb Vasc Biol 2021; 41:512-522. [PMID: 33327750 PMCID: PMC7770018 DOI: 10.1161/atvbaha.120.315435] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 10/26/2020] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV- controls. Approach and Results: We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV- controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV- serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV- controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=-1.59% [95% CI, -2.58% to -0.60%], P=0.002), even after covariate adjustment (β=-1.36% [95% CI, -2.46% to -0.47%], P=0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=-1.90% [95% CI, -2.58% to -1.21%], P<0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD. CONCLUSIONS The significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease.
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Affiliation(s)
- James H. Stein
- University of Wisconsin School of Medicine and Public Health; Madison, WI
| | - Noah Kime
- University of Washington Collaborative Health Studies Coordinating Center, Seattle, WA
| | - Claudia E. Korcarz
- University of Wisconsin School of Medicine and Public Health; Madison, WI
| | | | - Judith S. Currier
- David Geffen School of Medicine at University of California -Los Angeles; Los Angeles, CA
| | - Joseph C. Delaney
- University of Washington Collaborative Health Studies Coordinating Center, Seattle, WA
- College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba; Winnipeg, MB
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Temu TM, Zifodya JS, Polyak SJ, Wagoner J, Wanjalla CN, Masyuko S, Nyabiage J, Kinuthia J, Bloomfield GS, Page ST, Farquhar C. Antiretroviral therapy reduces but does not normalize immune and vascular inflammatory markers in adults with chronic HIV infection in Kenya. AIDS 2021; 35:45-51. [PMID: 33055570 PMCID: PMC7718419 DOI: 10.1097/qad.0000000000002729] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART). DESIGN Cross-sectional study. METHODS We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors. RESULTS Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1. CONCLUSION HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.
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Affiliation(s)
- Tecla M Temu
- Department of Global Health, University of Washington, Seattle, Washington
| | - Jerry S Zifodya
- Department of Medicine, Tulane University, New Orleans, Louisiana
| | - Stephen J Polyak
- Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Jessica Wagoner
- Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | | | - Sarah Masyuko
- Department of Global Health, University of Washington, Seattle, Washington
- Ministry of Health
- Kenyatta National Hospital, Nairobi, Kenya
| | - Jerusha Nyabiage
- Department of Global Health, University of Washington, Seattle, Washington
| | | | - Gerald S Bloomfield
- Department of Medicine and Duke Global Health Institute, Duke University, Durham, North Carolina
| | | | - Carey Farquhar
- Department of Global Health, University of Washington, Seattle, Washington
- Department of Medicine
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
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Masyuko SJ, Page ST, Polyak SJ, Kinuthia J, Osoti AO, Otieno FC, Kibachio JM, Mogaka JN, Macharia PM, Chohan BH, Wogner J, O'Connor A, Temu TM, Zifodya JS, Otedo A, Nakanjako D, Hughes JP, Farquhar C. Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression. Clin Infect Dis 2020; 73:e2034-e2042. [PMID: 33313687 DOI: 10.1093/cid/ciaa1650] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. METHODS We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1β, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. RESULTS We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4-10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1β (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). CONCLUSIONS We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.
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Affiliation(s)
- Sarah J Masyuko
- Ministry of Health, Nairobi, Kenya.,Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Stephanie T Page
- Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Stephen J Polyak
- Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - John Kinuthia
- Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya
| | - Alfred O Osoti
- Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya
| | - Fredrick C Otieno
- Department of Clinical Medicine and Therapeutics, College of Health Sciences, University of Nairobi, Nairobi, Kenya
| | | | - Jerusha N Mogaka
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | | | - Bhavna H Chohan
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Jessica Wogner
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Aidan O'Connor
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Tecla M Temu
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Jerry S Zifodya
- Department of Medicine, Tulane University, New Orleans, Louisiana, USA
| | | | - Damalie Nakanjako
- Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - James P Hughes
- Department of Biostatistics, University of Washington, Seattle, Washington, USA
| | - Carey Farquhar
- Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Medicine, University of Washington, Seattle, Washington, USA.,Department of Epidemiology, University of Washington, Seattle, Washington, USA
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Reyes-Retana JA, Duque-Ossa LC. Acute Myocardial Infarction Biosensor: A Review From Bottom Up. Curr Probl Cardiol 2020; 46:100739. [PMID: 33250264 DOI: 10.1016/j.cpcardiol.2020.100739] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 10/27/2020] [Indexed: 02/09/2023]
Abstract
Acute myocardial infarction (AMI) is a cardiovascular disease that is produced due to a deficiency of oxygen generating irreversible damage in the heart muscle. In diagnosis, electrocardiogram (ECG) investigation has been the main method but is insufficient, so approaches like the measurement of biomarkers levels in plasma or saliva have become one of the most commonly applied strategies for prognosis of AMI, as some of them are specifically related to a heart attack. Many tests are carrying on to determine biological markers changes, but usually, they present disadvantages related to time consumption and laborious work. To overcome the issues, researchers around the world have been developing different ways to enhance detection through the use of biosensors. These diagnostic devices have a biological sensing element associated to a physicochemical transducer that can be made from different materials and configurations giving place to different kinds of detection: Electrical/Electrochemical, Optical and Mechanical. In this review, the authors presents relevant investigations related to the most important biomarkers and biosensors used for their detection having in mind the nanotechnology participation in the process through the application of nanostructures as a good choice for device configuration.
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Affiliation(s)
- J A Reyes-Retana
- Tecnologico de Monterrey, School of Engineering and Science, Av. Carlos Lazo 100, Santa Fe, La Loma, Mexico City 01389, Mexico. https://tec.mx
| | - L C Duque-Ossa
- Tecnologico de Monterrey, School of Engineering and Science, Av. Carlos Lazo 100, Santa Fe, La Loma, Mexico City 01389, Mexico. https://tec.mx
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46
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Haile ZT, Sarfo B, Bonney EY, Mensah EA, Deletsu S. Association between Antiretroviral Treatment and Markers of Systemic Inflammation among HIV Patients in Ghana. Curr HIV Res 2020; 18:466-474. [PMID: 32807057 DOI: 10.2174/1570162x18666200817111152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 06/27/2020] [Accepted: 07/17/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Studies from high-income countries have reported that even after receiving antiretroviral treatment (ART), HIV-infected adults may not achieve normal levels of certain inflammatory markers that are known to be associated with the onset and development of non-communicable diseases. OBJECTIVE The aim of this study is to examine the relationship between ART and markers of systemic inflammation in HIV/AIDS patients at an urban antiretroviral clinic in Ghana. METHODS We examined serum levels of high sensitivity CRP (hsCRP), interleukin-6 (IL-6), interleukin- 18(IL-18), and tumor necrosis factor-α (sTNFR1 and sTNFR2) from 40 HIV infected patients. Kruskal-Wallis Test was used to examine the differences in markers of systemic inflammation according to the types of ART medication taken. We then utilized generalized additive models (GAM) with non-linear function to examine the association between ART and markers of systemic inflammation after adjusting for potential confounders. RESULTS Overall, 30 (75.0%) of the participants received ART and 35 (85%) were female. Kruskal- Wallis Test revealed no significant differences in the markers of systemic inflammation among the three categories of ART (none, AZT, 3TC, EFV/NVP, and TDF, 3TC/FTC, EFV/NVP). In the multivariable- adjusted GAM model, we found a significant but non-linear association between time since diagnosis and CRP levels (p=0.006). CONCLUSION Although the relatively small sample size limits the scope of the study's findings, these results suggest that individuals on ART need to be screened periodically for the development of chronic conditions. This line of investigation has the potential to influence treatment and clinical guidelines that will improve the quality of care for HIV-infected patients.
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Affiliation(s)
- Zelalem T Haile
- Department of Social Medicine, Ohio University Heritage College of Osteopathic Medicine, Dublin OH-43016, United States
| | - Bismark Sarfo
- Department of Epidemiology and Disease Control, University of Ghana School of Public Health, Legon, Ghana
| | - Evelyn Y Bonney
- Department of Virology, University of Ghana Noguchi Memorial Institute for Medical Research, Legon, Ghana
| | - Eric A Mensah
- Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana
| | - Selase Deletsu
- Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana
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47
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Bloch M, John M, Smith D, Rasmussen TA, Wright E. Managing HIV-associated inflammation and ageing in the era of modern ART. HIV Med 2020; 21 Suppl 3:2-16. [PMID: 33022087 DOI: 10.1111/hiv.12952] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. METHODS Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. RESULTS The changing natural history and demographics of human immunodeficiency virus (HIV)-infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life-threatening AIDS-related complications. From initial monotherapy with first-generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co-morbidities associated with HIV-infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non-AIDS-related co-morbidities are caused, at least in part, by persistent, low-grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. CONCLUSIONS In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.
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Affiliation(s)
- M Bloch
- Holdsworth House Medical Practice, Sydney, NSW, Australia.,Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - M John
- Kirby Institute, University of New South Wales, Sydney, NSW, Australia.,Royal Perth Hospital, Perth, WA, Australia.,Institute of Immunology and Infectious Disease, Perth, WA, Australia
| | - D Smith
- School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia.,The Albion Centre, Sydney, NSW, Australia
| | - T A Rasmussen
- Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia.,University of Melbourne, Melbourne, Vic., Australia
| | - E Wright
- The Alfred Hospital, Melbourne, Vic., Australia.,Centre for Inflammatory Diseases, Monash University, Melbourne, Vic., Australia.,The Burnett Institute, Melbourne, Vic., Australia
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48
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Bowman ER, Cameron CM, Richardson B, Kulkarni M, Gabriel J, Cichon MJ, Riedl KM, Mustafa Y, Cartwright M, Snyder B, Raman SV, Zidar DA, Koletar SL, Playford MP, Mehta NN, Sieg SF, Freeman ML, Lederman MM, Cameron MJ, Funderburg NT. Macrophage maturation from blood monocytes is altered in people with HIV, and is linked to serum lipid profiles and activation indices: A model for studying atherogenic mechanisms. PLoS Pathog 2020; 16:e1008869. [PMID: 33002093 PMCID: PMC7553323 DOI: 10.1371/journal.ppat.1008869] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/13/2020] [Accepted: 08/10/2020] [Indexed: 12/20/2022] Open
Abstract
People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes are enriched in PWH; however, little is known regarding monocyte-derived macrophages (MDMs) that may drive atherosclerosis in this population. We isolated PBMCs from people with and without HIV, and cultured these cells for 5 days in medium containing autologous serum to generate MDMs. Differential gene expression (DGE) analysis of MDMs from PWH identified broad alterations in innate immune signaling (IL-1β, TLR expression, PPAR βδ) and lipid processing (LXR/RXR, ACPP, SREBP1). Transcriptional changes aligned with the functional capabilities of these cells. Expression of activation markers and innate immune receptors (CD163, TLR4, and CD300e) was altered on MDMs from PWH, and these cells produced more TNFα, reactive oxygen species (ROS), and matrix metalloproteinases (MMPs) than did cells from people without HIV. MDMs from PWH also had greater lipid accumulation and uptake of oxidized LDL. PWH had increased serum levels of free fatty acids (FFAs) and ceramides, with enrichment of saturated FAs and a reduction in polyunsaturated FAs. Levels of lipid classes and species that are associated with CVD correlated with unique DGE signatures and altered metabolic pathway activation in MDMs from PWH. Here, we show that MDMs from PWH display a pro-atherogenic phenotype; they readily form foam cells, have altered transcriptional profiles, and produce mediators that likely contribute to accelerated ASCVD. People with HIV (PWH) are at greater risk for developing cardiovascular disease (CVD) than the general public, but the mechanisms underlying this increased risk are poorly understood. Macrophages play key roles in the pathogenesis of atherosclerosis, and are potential targets for therapeutic intervention. Here, we investigate phenotypic and functional abnormalities in monocyte-derived macrophages (MDMs) isolated from PWH that may drive CVD risk in this population. MDMs were differentiated in the presence of autologous serum, enabling us to explore the contributions of serum components (lipids, inflammatory cytokines, microbial products) as drivers of altered MDM function. We link serum levels of inflammatory biomarkers and CVD-associated lipid species to MDM activation. Our study provides new insight into drivers of pro-atherogenic MDM phenotype in PWH, and identifies directions for future study and potential intervention strategies to mitigate CVD risk.
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Affiliation(s)
- Emily R. Bowman
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America
- * E-mail:
| | - Cheryl M. Cameron
- Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Brian Richardson
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Manjusha Kulkarni
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America
| | - Janelle Gabriel
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America
| | - Morgan J. Cichon
- Department of Food Science & Technology and the Nutrient & Phytochemical Shared Resource, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America
| | - Kenneth M. Riedl
- Department of Food Science & Technology and the Nutrient & Phytochemical Shared Resource, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America
| | - Yousef Mustafa
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Michael Cartwright
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Brandon Snyder
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America
| | - Subha V. Raman
- Department of Internal Medicine, Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio, United States of America
| | - David A. Zidar
- Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America
| | - Susan L. Koletar
- Department of Medicine, Division of Infectious Diseases, Ohio State University, Columbus, Ohio, United States of America
| | - Martin P. Playford
- Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Nehal N. Mehta
- Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Scott F. Sieg
- Department of Medicine, Division of Infectious Diseases and HIV Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, United States of America
| | - Michael L. Freeman
- Department of Medicine, Division of Infectious Diseases and HIV Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, United States of America
| | - Michael M. Lederman
- Department of Medicine, Division of Infectious Diseases and HIV Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, United States of America
| | - Mark J. Cameron
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America
| | - Nicholas T. Funderburg
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America
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49
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Temu TM, Polyak SJ, Zifodya JS, Wanjalla CN, Koethe JR, Masyuko S, Nyabiage J, Kinuthia J, Gervassi AL, Oyugi J, Page S, Farquhar C. Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya. Open Forum Infect Dis 2020; 7:ofaa425. [PMID: 33094120 PMCID: PMC7568437 DOI: 10.1093/ofid/ofaa425] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/10/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Residual monocyte activation may contribute to increased risk for endothelial dysfunction and subsequent atherosclerotic cardiovascular diseases (CVDs) among people with HIV (PWH) on antiretroviral therapy (ART). We examined the relationship between monocyte activation and endothelial activation in PWH in Kenya. METHODS Serum levels of markers of endothelial activation (soluble/circulating intercellular [sICAM-1] and vascular [sVCAM-1] cell adhesion molecule-1), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and monocyte activation (soluble CD14 [sCD14]) were measured in 275 PWH on ART and 266 HIV-negative persons. Linear regression was used to evaluate associations, adjusting for demographic and traditional CVD risk factors. RESULTS Among 541 participants, the median age was 43 years, 50% were female, and most PWH were virally suppressed (97%). sICAM-1 and sVCAM-1 levels were significantly higher in PWH than in HIV-negative participants (P < .001 for both). After further adjustment for traditional CVD risk factors, HIV infection remained associated with 49% (95% CI, 33% to 67%) greater sICAM-1 and 30% (95% CI, 14% to 48%) greater sVCAM-1 relative to uninfected controls. Adjustment for sCD14 substantially attenuated the difference between PWH and HIV-negative individuals. In a stratified analysis of PWH, both sICAM-1 and sVCAM-1 were positively associated with sCD14 (P < .001). CONCLUSIONS Despite viral suppression, African PWH have evidence of enhanced endothelial activation associated with sCD14, suggesting that monocyte activation plays a role in atherosclerotic plaque development. Future studies are needed to determine mechanistic pathways leading to monocyte activation in this population.
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Affiliation(s)
- Tecla M Temu
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Stephen J Polyak
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
| | - Jerry S Zifodya
- Department of Medicine, Tulane University, New Orleans, Louisiana, USA
| | | | - John R Koethe
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Sarah Masyuko
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Jerusha Nyabiage
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - John Kinuthia
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Kenyatta National Hospital, Nairobi, Kenya
| | - Ana L Gervassi
- Center for Infectious Disease Research, Seattle Biomedical Research Institute, Seattle, Washington, USA
| | - Julius Oyugi
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
| | - Stephanie Page
- Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA
| | - Carey Farquhar
- Department of Global Health, University of Washington, Seattle, Washington, USA
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50
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Tindle HA, Freiberg MS, Gnatienko N, Blokhina E, Cheng DM, Yaroslavtseva T, Bendiks S, Winter M, Krupitsky E, Samet JH. Design of a randomized controlled trial of smoking cessation medications for alcohol reduction among HIV-positive heavy drinkers and daily smokers in St. Petersburg, Russia. Contemp Clin Trials Commun 2020; 19:100625. [PMID: 33659761 PMCID: PMC7889999 DOI: 10.1016/j.conctc.2020.100625] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 07/08/2020] [Accepted: 07/13/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND HIV, heavy drinking, and smoking are all pro-inflammatory and increase risk for coronary heart disease (CHD). Interventions that reduce alcohol use, smoking, or both in HIV-positive people could lower inflammation, CHD and death risk. Varenicline and cytisine are proven therapies for smoking cessation and may also reduce alcohol consumption. The comparative efficacy of varenicline and cytisine to reduce alcohol consumption has not been tested, nor has their comparative effectiveness been reported for smoking. OBJECTIVE This paper describes the protocol of the Studying Partial agonists for Ethanol and Tobacco Elimination in Russians with HIV (St PETER HIV), a four-arm parallel-group randomized controlled trial comparing effects of varenicline, cytisine, and nicotine replacement therapy (NRT). METHODS The study is recruiting four hundred HIV-positive heavy drinking smokers interested in cutting down on alcohol and/or tobacco in St. Petersburg, Russia. Participants are randomly assigned to receive either active varenicline + NRT placebo, varenicline placebo + active NRT, active cytisine + NRT placebo, cytisine placebo + active NRT. All participants receive evidence-based counseling for alcohol and tobacco use, one active medication, and one placebo. Outcomes are: 1) % heavy drinking days in the past month (primary study outcome at three months) and alcohol craving; 2) cigarettes per day (primary smoking outcome at 3 months) and 7-day point prevalence abstinence and; 3) inflammation, CHD risk, and mortality risk. CONCLUSION St PETER HIV addresses the paucity of randomized controlled trial data to guide treatment of alcohol consumption and smoking in HIV-positive heavy drinking smokers.
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Affiliation(s)
- Hilary A. Tindle
- Vanderbilt Center for Tobacco, Addiction and Lifestyle (ViTAL), Vanderbilt University Medical Center, Division of General Internal Medicine & Public Health and Vanderbilt Ingram Cancer Center, 2525 West End, Suite 450, Nashville, TN, 37203, United States
- Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), Nashville, TN, United States
| | - Matthew S. Freiberg
- Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), Nashville, TN, United States
- Vanderbilt Center for Clinical Cardiovascular Trials Evaluation (V-C3REATE), Vanderbilt University Medical Center, Division of Cardiovascular Medicine, 2525 West End, Suite 300-A, Nashville, TN, 37203, United States
| | - Natalia Gnatienko
- Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, 801 Massachusetts Avenue, 2nd Floor, Boston, MA, 02118, United States
| | - Elena Blokhina
- Pavlov University, Lev Tolstoy St. 6-8, St. Petersburg, 197022, Russian Federation
| | - Debbie M. Cheng
- Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, 3rd Floor, Boston, MA, 02118, United States
| | | | - Sally Bendiks
- Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, 801 Massachusetts Avenue, 2nd Floor, Boston, MA, 02118, United States
| | - Michael Winter
- Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, 85 East Newton Street, 9th Floor, Boston, MA 02118, United States Pasteur Research Institute of Epidemiology and Microbiology, Russian Federation, Mira St. 14, St. Petersburg, 197101, Russian Federation
| | - Evgeny Krupitsky
- Pavlov University, Lev Tolstoy St. 6-8, St. Petersburg, 197022, Russian Federation
- Bekhterev National Medical Research Center for Psychiatry and Neurology, Bekhtereva St., 3, St. Petersburg, 192019, Russian Federation
| | - Jeffrey H. Samet
- Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine/Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, 801 Massachusetts Avenue, 2nd Floor, Boston, MA, 02118, United States
- Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Avenue, 2nd Floor, Boston, MA, 02118, United States
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