|
1
|
Tanner MR, O’Shea JG, Byrd KM, Johnston M, Dumitru GG, Le JN, Lale A, Byrd KK, Cholli P, Kamitani E, Zhu W, Hoover KW, Kourtis AP. Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV - CDC Recommendations, United States, 2025. MMWR Recomm Rep 2025; 74:1-56. [PMID: 40331832 PMCID: PMC12064164 DOI: 10.15585/mmwr.rr7401a1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2025] Open
Abstract
Nonoccupational postexposure prophylaxis (nPEP) for HIV is recommended when a nonoccupational (e.g., sexual, needle, or other) exposure to nonintact skin or mucous membranes that presents a substantial risk for HIV transmission has occurred, and the source has HIV without sustained viral suppression or their viral suppression information is not known. A rapid HIV test (also referred to as point-of-care) or laboratory-based antigen/antibody combination HIV test is recommended before nPEP initiation. Health care professionals should ensure the first dose of nPEP is provided as soon as possible, and ideally within 24 hours, but no later than 72 hours after exposure. The initial nPEP dose should not be delayed due to pending results of any laboratory-based testing, and the recommended length of nPEP course is 28 days. The recommendations in these guidelines update the 2016 nPEP guidelines (CDC. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. Atlanta, GA: US Department of Health and Human Services, CDC; 2017). These 2025 nPEP guidelines update recommendations and considerations for use of HIV nPEP in the United States to include newer antiretroviral (ARV) agents, updated nPEP indication considerations, and emerging nPEP implementation strategies. The guidelines also include considerations for testing and nPEP regimens for persons exposed who have received long-acting injectable ARVs in the past. Lastly, testing recommendations for persons who experienced sexual assault were updated to align with the most recent CDC sexually transmitted infection treatment guidelines. These guidelines are divided into two sections: Recommendations and CDC Guidance. The preferred regimens for most adults and adolescents are now bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine). However, the regimen can be tailored to the clinical circumstances. Medical follow-up for persons prescribed nPEP also should be tailored to the clinical situation; recommended follow-up includes a visit at 24 hours (remote or in person) with a medical provider, and clinical follow-up 4-6 weeks and 12 weeks after exposure for laboratory testing. Persons initiating nPEP should be informed that pre-exposure prophylaxis for HIV (PrEP) can reduce their risk for acquiring HIV if they will have repeat or continuing exposure to HIV after the end of the nPEP course. Health care professionals should offer PrEP options to persons with ongoing indications for PrEP and create an nPEP-to-PrEP transition plan for persons who accept PrEP.
Collapse
|
|
2
|
Hudson JA, Ferrand RA, Gitau SN, Mureithi MW, Maffia P, Alam SR, Shah ASV. HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology. Circ Res 2024; 134:1546-1565. [PMID: 38781300 DOI: 10.1161/circresaha.124.323890] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.
Collapse
Affiliation(s)
- Jonathan A Hudson
- Kings College London BHF Centre, School of Cardiovascular and Metabolic Medicine & Sciences, United Kingdom (J.A.H.)
| | - Rashida A Ferrand
- Department of Clinical Research (R.A.F.), London School of Hygiene and Tropical Medicine, United Kingdom
- Biomedical Research and Training Institute, Harare, Zimbabwe (R.A.F.)
| | - Samuel N Gitau
- Department of Radiology, Aga Khan University Nairobi, Kenya (S.N.G.)
| | - Marianne Wanjiru Mureithi
- Department of Medical Microbiology and Immunology, Faculty of Health Sciences (M.W.M.), University of Nairobi, Kenya
| | - Pasquale Maffia
- School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom (P.M.)
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Italy (P.M.)
- Africa-Europe Cluster of Research Excellence in Non-Communicable Diseases and Multimorbidity, African Research Universities Alliance and The Guild of European Research-Intensive Universities, Glasgow, United Kingdom (P.M.)
| | - Shirjel R Alam
- Department of Cardiology, North Bristol NHS Trust, United Kingdom (S.R.A.)
| | - Anoop S V Shah
- Department of Non-Communicable Disease Epidemiology (A.S.V.S.), London School of Hygiene and Tropical Medicine, United Kingdom
- Department of Cardiology, Imperial College NHS Trust, London, United Kingdom (A.S.V.S.)
| |
Collapse
|
|
3
|
Srichatrapimuk S, Wongsa A, Sungkanuparph S, Kiertiburanakul S, Tassaneetrithep B, Phuphuakrat A. Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study. AIDS Res Ther 2023; 20:13. [PMID: 36849967 PMCID: PMC9969700 DOI: 10.1186/s12981-023-00506-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 02/15/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND Chronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV receiving ART. METHODS A randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavastatin or placebo were investigated. RESULTS A total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41-54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm3. The median duration of ATV/r use was 36 (24-48) months. Significant change in levels of basic fibroblast growth factor (FGF) between pitavastatin treatment and placebo at week 12 from baseline was observed (27.1 vs. 20.5 pg/mL; p=0.023). However, there were no significant changes from baseline of hs-CRP and other plasma cytokine levels at week 12 of pitavastatin or placebo. Regarding cellular markers, percentages of HLA-DR+CD38-CD4+ T cells and PD1+CD4+ T cells significantly decreased from baseline in PLHIV receiving pitavastatin for 12 weeks, as compared to placebo (- 0.27 vs. 0.02%; p=0.049 and - 0.23 vs. 0.23%; p=0.022, respectively). CONCLUSIONS Pitavastatin treatment increases basic FGF levels, and lowers HLA-DR+CD38-CD4+ T cells, and PD1+CD4+ T cells. Further study on the effects of pitavastatin on preventing cardiovascular diseases in PLHIV should be pursued.
Collapse
Affiliation(s)
- Sirawat Srichatrapimuk
- grid.10223.320000 0004 1937 0490 Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Artit Wongsa
- grid.10223.320000 0004 1937 0490Center of Research Excellence in Immunoregulation, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Somnuek Sungkanuparph
- grid.10223.320000 0004 1937 0490 Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Sasisopin Kiertiburanakul
- grid.10223.320000 0004 1937 0490Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400 Thailand
| | - Boonrat Tassaneetrithep
- grid.10223.320000 0004 1937 0490Center of Research Excellence in Immunoregulation, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Angsana Phuphuakrat
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
| |
Collapse
|
|
4
|
Ramos SR, Fraser M, Araya F, Kim HY, Parrilla JAS, Sy KM, Nagpal RT, Camacho-Rivera M, Boutjdir M. Community-Engaged Intervention Mapping for Cardiovascular Disease Prevention in Black and Latinx Sexual Minority Men With HIV in New York City: Protocol for a Web-Based Mixed Methods Study. JMIR Res Protoc 2022; 11:e41602. [PMID: 36130735 PMCID: PMC9597416 DOI: 10.2196/41602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Approximately every 37 seconds, someone in the United States dies of cardiovascular disease (CVD). It has emerged as an important contributor to morbidity among persons with HIV. Black and Latinx sexual minority men are at higher risk of both HIV and CVD when compared to heterosexual, nonethnic or minority men. Persons with HIV have a 1.5 to 2-times risk of having CVD than do HIV-negative persons. Data suggest that by the year 2030, an estimated 78% of persons with HIV will have CVD. The relationship between HIV and CVD in marginalized populations is not well understood because overall awareness of HIV and CVD as comorbid conditions is low, which further heightens risk. This has created a critically pressing issue affecting underrepresented ethnic and racial populations with HIV and requires immediate efforts to mitigate risk. OBJECTIVE The purpose of this formative, mixed methods study is to use a community-engaged approach to map a behavioral intervention for CVD prevention in Black and Latinx sexual minority men with HIV in New York City. METHODS Literature reviews focused on behavioral prevention studies using intervention mapping. In Aim 1, we will use qualitative interviews with HIV program managers and community members to understand facilitators and barriers to CVD prevention, chronic illnesses of concern, and early design elements needed for a web-based CVD prevention intervention. In Aim 2, we will conduct qualitative interviews and administer cross-sectional validated surveys with 30 Black and Latinx sexual minority men with HIV. We will assess illness perceptions of chronic conditions, such as HIV, hypertension, and diabetes. A total of 40 participants (program managers and community members) for Aims 1 and 2 will be enrolled to participate. To develop the protocol, we will follow steps 1 through 3 (needs assessment, change objectives, implementation strategy) of intervention mapping, using mixed methods. RESULTS The study was approved by New York University Institutional Review Board in February 2021 (IRB-FY2021-4772) and also by the Yale University Institutional Review Board in June 2022 (#2000031577). We anticipate completing data collection on or before December 2022. Early analyses suggested concerns about illnesses outside of HIV and associated comorbid conditions, such as COVID-19 and monkeypox. Additionally, we noted a strong interest in using a web-based platform for CVD prevention education. CONCLUSIONS Web-based, behavioral, CVD prevention interventions may be promising modalities to closing the cardiovascular health disparities gap in Black and Latinx sexual minority men with HIV by extending the reach of prevention interventions using community-informed approaches and technological modalities that have been underused in this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR1-10.2196/41602.
Collapse
Affiliation(s)
- S Raquel Ramos
- School of Nursing, Yale University, Orange, CT, United States
- School of Public Health, Social and Behavioral Sciences, Yale University, New Haven, CT, United States
| | - Marilyn Fraser
- Arthur Ashe Institute for Urban Health, Brooklyn, NY, United States
| | - Faven Araya
- Arthur Ashe Institute for Urban Health, Brooklyn, NY, United States
| | - Hyun Young Kim
- College of Nursing, New York University, New York, NY, United States
| | - Jon Andre Sabio Parrilla
- School of Public Health, Social and Behavioral Sciences, Yale University, New Haven, CT, United States
| | - Kalla Maxine Sy
- School of Public Health, Social and Behavioral Sciences, Yale University, New Haven, CT, United States
| | | | - Marlene Camacho-Rivera
- School of Public Health, State University of New York Downstate Health Sciences University, Brooklyn, NY, United States
| | - Mohamed Boutjdir
- Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn, NY, United States
- Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, NY, United States
- Department of Medicine, New York University School of Medicine, New York, NY, United States
| |
Collapse
|
|
5
|
Tian X, Yao Y, He G, Jia Y, Wang K, Chen L. Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database. Sci Rep 2021; 11:12438. [PMID: 34127681 PMCID: PMC8203613 DOI: 10.1038/s41598-021-91549-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/24/2021] [Indexed: 11/09/2022] Open
Abstract
This current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.
Collapse
Affiliation(s)
- Xiaojiang Tian
- Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, 400021, China
| | - Yao Yao
- Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, 400021, China
| | - Guanglin He
- Department of Anthropology and Ethnology, Institute of Anthropology, National Institute for Data Science in Health and Medicine, and School of Life Sciences, Xiamen University, Xiamen, 361005, China
| | - Yuntao Jia
- Department of Pharmacy, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
| | - Kejing Wang
- Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, 400021, China.
| | - Lin Chen
- Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, 400021, China.
| |
Collapse
|
|
6
|
Uccello G, Mollace R, Stelitano M, Tavernese A, Muscoli S, Di Luozzo M, De Vico P, Romeo F, Cammalleri V. Clinical and angiographical features of first episode of acute coronary syndrome in patients with human immunodeficiency virus infection. HIV Res Clin Pract 2021; 22:31-35. [PMID: 33876716 DOI: 10.1080/25787489.2021.1911502] [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
BACKGROUND Patients affected by the human immunodeficiency virus (HIV) show an increased risk of myocardial infarction. Clinical and angiographic features of HIV positive (HIV+) patients presenting with the first episode of an acute coronary syndrome (ACS) are not well defined in previous studies. OBJECTIVE To demonstrate that HIV + patients with acute coronary syndrome had different features than non-HIV patients. METHODS We identified 48 HIV + patients without previous cardiovascular events admitted to our Emergency Department with ACS diagnosis between 2012 and 2020. Clinical and angiographic characteristics were compared with a control group of 48 non-HIV consecutive patients affected by ACS as first episode. RESULTS HIV + patients were most frequently men (87.5% vs 62.5%, p = 0.009) and younger about a decade (mean age 53.8 ± 8.2 vs 63.7 ± 11.9 years old, p < 0.0001); statistically significant hypertriglyceridemia has been found in the HIV group (178,6 ± 59,8 mg/dl vs 142,7 ± 63,7 mg/dl, p = 0.005). HIV(+) patients had a higher rate of anterior ST-elevation myocardial infarction (STEMI) (65% vs 33%, p = 0.03) and significant lesions on left anterior descending (LAD) coronary artery (83% vs 58% p = 0.01). CONCLUSIONS HIV + patients with the first episode of ACS are generally young men with higher triglycerides and most frequently presenting with anterior STEMI and LAD involvement. The strict control of risk factors and a program for the early identification of coronary artery disease are strongly recommended in this subset of patients.
Collapse
Affiliation(s)
- Giuseppe Uccello
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Rocco Mollace
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Maria Stelitano
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Annamaria Tavernese
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Saverio Muscoli
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Marco Di Luozzo
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Pasquale De Vico
- Department of Anaesthesia, University of Rome "Tor Vergata", Rome, Italy
| | - Francesco Romeo
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| | - Valeria Cammalleri
- Department of Cardiovascular Disease, University of Rome "Tor Vergata", Rome, Italy
| |
Collapse
|
|
7
|
Triant VA, Siedner MJ. Darunavir and Cardiovascular Risk: Evaluating the Data to Inform Clinical Care. J Infect Dis 2020; 221:498-500. [PMID: 31828327 DOI: 10.1093/infdis/jiz482] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 10/09/2019] [Indexed: 12/24/2022] 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.,Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Mark J Siedner
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA.,Africa Health Research Institute, KwaZulu-Nata, South Africa
| |
Collapse
|
|
8
|
Mizushima D, Dung NTH, Dung NT, Matsumoto S, Tanuma J, Gatanaga H, Trung NV, Kinh NV, Oka S. Dyslipidemia and cardiovascular disease in Vietnamese people with HIV on antiretroviral therapy. Glob Health Med 2020; 2:39-43. [PMID: 33330773 DOI: 10.35772/ghm.2019.01035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/10/2020] [Accepted: 02/19/2020] [Indexed: 11/08/2022]
Abstract
With expanding antiretroviral therapy (ART) in Vietnam, the use of second-line ART with ritonavir-boosted lopinavir (LPV/r) is increasing. However, little is known regarding the effect of LPV/r on dyslipidemia (DL) and cardiovascular disease (CVD) in people with HIV in Vietnam. A cross-sectional study was performed in a cohort of HIV-infected Vietnamese patients on ART at the National Hospital for Tropical Diseases in Hanoi, Vietnam. In addition to DL, we included hypertension (HT) and hyperglycemia (HG) as non-communicable diseases. Blood pressure, casual blood sugar levels, and the lipid profile were evaluated cross-sectionally in October and November 2016. The incidence of CVD was calculated in the cohort. We determined factors associated with diseases by univariate and multivariate analyses. A total of 1,346 subjects were evaluated for their non-communicable diseases. The subjects' mean age was 39.2 years and 41.8% were women. A total of 10.5% of the subjects had exposure to LPV/r. DL, HT, and HG was diagnosed in 53.5%, 24.4%, and 0.8% of the subjects, respectively. In multivariate analysis, age (OR = 1.040; 95% CI, 1.025-1.055), female sex (OR = 0.335; 95% CI, 0.264-0.424), and LPV/r exposure (OR = 3.251; 95% CI, 2.030-5.207) were significantly associated with DL. The incidence rate of CVD was 1.87/1,000 person-years (15 incidental cases in 8,013 person-years). LPV/r exposure was not a risk factor for the incidence of CVD. Although a causative relation with LPV/r and CVD was not identified in this study, attention should be paid to CVD for patients on LPV/r in the future.
Collapse
Affiliation(s)
- Daisuke Mizushima
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | | | | | - Shoko Matsumoto
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Junko Tanuma
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroyuki Gatanaga
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.,Center for AIDS Research, Kumamoto University, Kumamoto, Japan
| | | | | | - Shinichi Oka
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.,Center for AIDS Research, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
|
9
|
Abstract
Antiretroviral therapy has largely transformed HIV infection into a chronic disease condition. As such, physicians and other providers caring for individuals living with HIV infection need to be aware of the potential cardiovascular complications of HIV infection and the nuances of how HIV infection increases the risk of cardiovascular diseases, including acute myocardial infarction, stroke, peripheral artery disease, heart failure and sudden cardiac death, as well as how to select available therapies to reduce this risk. In this Review, we discuss the epidemiology and clinical features of cardiovascular disease, with a focus on coronary heart disease, in the setting of HIV infection, which includes a substantially increased risk of myocardial infarction even when the HIV infection is well controlled. We also discuss the mechanisms underlying HIV-associated atherosclerotic cardiovascular disease, such as the high rates of traditional cardiovascular risk factors in patients with HIV infection and HIV-related factors, including the use of antiretroviral therapy and chronic inflammation in the setting of effectively treated HIV infection. Finally, we highlight available therapeutic strategies, as well as approaches under investigation, to reduce the risk of cardiovascular disease and lower inflammation in patients with HIV infection.
Collapse
Affiliation(s)
- Priscilla Y Hsue
- University of California-San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.
| | - David D Waters
- University of California-San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA
| |
Collapse
|
|
10
|
Two-drug regimens with dolutegravir for maintaining viral suppression: looking at the right companion. AIDS 2019; 33:2264-2266. [PMID: 31688045 DOI: 10.1097/qad.0000000000002329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
11
|
Brief Report: Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid Atherosclerosis in HIV-Infected Patients on Virological Suppression. J Acquir Immune Defic Syndr 2019; 79:617-623. [PMID: 30204718 DOI: 10.1097/qai.0000000000001854] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1-infected patients on virological suppression. DESIGN Retrospective study on adult HIV-1-infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and without previous cardiovascular events. METHODS Intima media thickness was measured in 4 segments: carotid common artery and bifurcation on the left and right sides. Carotid lesion was defined as an intima media thickness ≥1.5 mm in ≥1 region at CUS. Patients were classified as: normal if all bilirubin values before CUS were below the upper normal limit and with hyperbilirubinemia if ≥1 bilirubin value above upper normal limit before CUS was recorded. Multivariate logistic regression was used to determine whether hyperbilirubinemia showed association with the presence of ≥1 carotid lesion, after adjusting for confounding factors. RESULTS Overall, 903 patients were evaluated, 511 with ≥1 and 392 without carotid lesions. At multivariate analysis, total [adjusted odds ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62 (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions in addition to younger age, negative hepatitis C virus antibodies, higher nadir CD4, lower low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir treatment on carotid lesions was detected. CONCLUSIONS In HIV-1-treated patients, total or indirect hyperbilirubinemia was likely associated with the absence of carotid lesions.
Collapse
|
|
12
|
Afonso P, Auclair M, Caron-Debarle M, Capeau J. Impact of CCR5, integrase and protease inhibitors on human endothelial cell function, stress, inflammation and senescence. Antivir Ther 2019; 22:645-657. [PMID: 28350300 DOI: 10.3851/imp3160] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Ageing HIV-infected patients present an increased incidence of cardiovascular diseases, endothelial dysfunction being an early alteration. Some protease inhibitors (PIs) have been shown to increase the risk of cardiovascular disease. We evaluated here the effects of CCR5 or integrase inhibitors as compared to PIs on endothelial functions in vitro. METHODS Human coronary artery endothelial cells (HCAEC) from adult and old non-HIV-infected donors were treated for 15 days with the CCR5 inhibitor maraviroc, the integrase inhibitors dolutegravir or raltegravir or the ritonavir-boosted PIs, darunavir (DRV/r) or atazanavir (ATV/r), all at Cmax concentrations. We evaluated endothelial function, secretion of adhesion molecules and cytokines, inflammation, oxidative stress and senescence. RESULTS In endothelial cells from adult donors, we confirmed that ATV/r and DRV/r adversely affected all assessed endothelial functions and enhanced senescence, these effects being mild for DRV/r. Raltegravir had no effect and maraviroc a mild anti-inflammatory effect. Dolutegravir decreased inflammation, by inhibiting the NFκB pathway, and senescence, by repressing the p21 pathway. Moreover, HCAEC from an old donor presented, constitutively, a high level of senescence. Raltegravir mildly affected inflammation and senescence while maraviroc and dolutegravir decreased oxidative stress, inflammation and senescence and improved endothelial dysfunction. CONCLUSIONS We report here that the integrase inhibitor dolutegravir and the CCR5 inhibitor maraviroc reduced inflammation of human adult endothelial cells to different extents while raltegravir was neutral. Dolutegravir also reduced senescence, while PI/r increased inflammation and senescence. It is important to address the clinical relevance of these results.
Collapse
Affiliation(s)
- Pauline Afonso
- Sorbonne Universités, UPMC Univ Paris 6, Paris, France.,Inserm UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Martine Auclair
- Sorbonne Universités, UPMC Univ Paris 6, Paris, France.,Inserm UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Martine Caron-Debarle
- Sorbonne Universités, UPMC Univ Paris 6, Paris, France.,Inserm UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Jacqueline Capeau
- Sorbonne Universités, UPMC Univ Paris 6, Paris, France.,Inserm UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.,ICAN, Institute of Cardiometabolism and Nutrition, Paris, France
| |
Collapse
|
|
13
|
Feinstein MJ, Hsue PY, Benjamin L, Bloomfield GS, Currier JS, Freiberg MS, Grinspoon SK, Levin J, Longenecker CT, Post. WS. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association. Circulation 2019; 140:e98-e124. [PMID: 31154814 PMCID: PMC7993364 DOI: 10.1161/cir.0000000000000695] [Citation(s) in RCA: 421] [Impact Index Per Article: 70.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
As early and effective antiretroviral therapy has become more widespread, HIV has transitioned from a progressive, fatal disease to a chronic, manageable disease marked by elevated risk of chronic comorbid diseases, including cardiovascular diseases (CVDs). Rates of myocardial infarction, heart failure, stroke, and other CVD manifestations, including pulmonary hypertension and sudden cardiac death, are significantly higher for people living with HIV than for uninfected control subjects, even in the setting of HIV viral suppression with effective antiretroviral therapy. These elevated risks generally persist after demographic and clinical risk factors are accounted for and may be partly attributed to chronic inflammation and immune dysregulation. Data on long-term CVD outcomes in HIV are limited by the relatively recent epidemiological transition of HIV to a chronic disease. Therefore, our understanding of CVD pathogenesis, prevention, and treatment in HIV relies on large observational studies, randomized controlled trials of HIV therapies that are underpowered to detect CVD end points, and small interventional studies examining surrogate CVD end points. The purpose of this document is to provide a thorough review of the existing evidence on HIV-associated CVD, in particular atherosclerotic CVD (including myocardial infarction and stroke) and heart failure, as well as pragmatic recommendations on how to approach CVD prevention and treatment in HIV in the absence of large-scale randomized controlled trial data. This statement is intended for clinicians caring for people with HIV, individuals living with HIV, and clinical and translational researchers interested in HIV-associated CVD.
Collapse
Affiliation(s)
| | - Priscilla Y. Hsue
- University of California-San Francisco School of Medicine, San Francisco, CA
| | | | | | - Judith S. Currier
- University of California-Los Angeles School of Medicine, Los Angeles, CA
| | | | | | - Jules Levin
- National AIDS Treatment Advocacy Program, New York, NY
| | | | - Wendy S. Post.
- Johns Hopkins University School of Medicine, Baltimore, MD
| |
Collapse
|
|
14
|
Chou R, Dana T, Grusing S, Bougatsos C. Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2019; 321:2337-2348. [PMID: 31184705 DOI: 10.1001/jama.2019.2592] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
IMPORTANCE Untreated HIV infection can result in significant morbidity, mortality, and HIV transmission. A 2012 review for the US Preventive Services Task Force (USPSTF) found antiretroviral therapy (ART) associated with improved clinical outcomes and decreased transmission risk in persons with CD4 cell counts less than 500/mm3. OBJECTIVE To update the 2012 review on HIV screening to inform the USPSTF. DATA SOURCES Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019. STUDY SELECTION Nonpregnant individuals 12 years and older; randomized clinical trials (RCTs) and controlled observational studies of screening vs no screening, alternative screening strategies, earlier vs later initiation of ART, and long-term harms of ART. DATA EXTRACTION AND SYNTHESIS One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. MAIN OUTCOMES AND MEASURES Mortality, AIDS events, quality of life, function, and HIV transmission; harms of screening and long-term (≥2 years) harms of ART; screening yield. RESULTS Eighteen new studies (5 RCTs, 11 cohort studies, and 2 systematic reviews; N = 266 563) were included, and 11 studies (2 RCTs and 9 cohort studies; N = 218 542) were carried forward from the prior USPSTF report. No study directly evaluated effects of HIV screening vs no screening on clinical outcomes or harms, or the yield of alternative screening strategies. Two newly identified RCTs conducted completely or partially in low-resource settings found ART initiation at CD4 cell counts greater than 500/mm3 associated with lower risk of a composite outcome of mortality, AIDS-defining events, or serious non-AIDS events (relative risk [RR], 0.44 [95% CI, 0.31-0.63] and RR, 0.57 [95% CI, 0.35-0.95]); results were consistent with those from a large observational study. Early ART was not associated with increased risk of cardiovascular events. Early ART initiation was associated with sustained reduction in risk of HIV transmission at 5.5 years (RR, 0.07 [95% CI, 0.02-0.22] for linked transmission). New evidence regarding the association between abacavir use and risk of cardiovascular events was inconsistent. Certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. CONCLUSIONS AND RELEVANCE In nonpregnant adolescents and adults there was no direct evidence on the clinical benefits and harms of screening for HIV infections vs no screening, or the yield of repeat or alternative screening strategies. New evidence extends effectiveness of ART to asymptomatic individuals with CD4 cell counts greater than 500/mm3 and shows sustained reduction in risk of HIV transmission at longer-term follow-up, although certain ART regimens may be associated with increased risk of long-term harms.
Collapse
Affiliation(s)
- Roger Chou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
- Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland
| | - Tracy Dana
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
| | - Sara Grusing
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
| | - Christina Bougatsos
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
| |
Collapse
|
|
15
|
Switch to dolutegravir and unboosted atazanavir in HIV-1 infected patients with undetectable viral load and long exposure to antiretroviral therapy. AIDS 2019; 33:1256-1260. [PMID: 30870194 DOI: 10.1097/qad.0000000000002188] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
: We evaluated the efficacy and safety of a two-drug regimen including dolutegravir (DTG) and unboosted atazanavir (uATV) in 151 HIV-1 infected patients with HIV-RNA of more than 50 copies/ml. During a median follow-up of 62 (42-97) weeks, two virological failures (1%) and 13 treatment discontinuations (9%) occurred; the 48-week probability of virological failure was 0.8% (95% confidence interval 0.2-5.6%). Switch to DTG + uATV may represent a boosting and transcriptase reverse inhibitors sparing otion in individuals with long exposure to antiretroviral therapy and risk of cardiovascular disease.
Collapse
|
|
16
|
Gurbel PA, deFilippi CR, Bliden KP, Tantry US. HIV infection, ACS, PCI and high platelet reactivity: ingredients for a perfect thrombotic storm. Eur Heart J 2019; 38:1687-1689. [PMID: 28087604 DOI: 10.1093/eurheartj/ehw630] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Paul A Gurbel
- Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Christopher R deFilippi
- Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Kevin P Bliden
- Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Udaya S Tantry
- Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Falls Church, VA, USA
| |
Collapse
|
|
17
|
Oswald DM, Sim ES, Baker C, Farhan O, Debanne SM, Morris NJ, Rodriguez BG, Jones MB, Cobb BA. Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections. FASEB J 2019; 33:1852-1859. [PMID: 30183373 PMCID: PMC6338643 DOI: 10.1096/fj.201800923r] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 08/06/2018] [Indexed: 12/30/2022]
Abstract
Despite effective control of HIV infection with antiretroviral drugs, individuals with HIV have high incidences of secondary diseases. These sequelae, such as cardiovascular disease (CVD), are poorly understood and represent a major health burden. To date, predictive biomarkers of HIV-associated secondary disease have been elusive, making preventative clinical management essentially impossible. Here, we applied a newly developed and easy to deploy, multitarget, and high-throughput glycomic analysis to banked HIV+ human plasma samples to determine whether the glycome may include biomarkers that predict future HIV-associated cardiovascular events or CVD diagnoses. Using 324 patient samples, we identified a glycomic fingerprint that was predictive of future CVD events but independent of CD4 counts, diabetes, age, and birth sex, suggesting that the plasma glycome may serve as a biomarker for specific HIV-associated sequelae. Our findings constitute the discovery of novel glycan biomarkers that could classify patients with HIV with elevated risk for CVD and reveal the untapped prognostic potential of the plasma glycome in human disease.-Oswald, D. M., Sim, E. S., Baker, C., Farhan, O., Debanne, S. M., Morris, N. J., Rodriguez, B. G., Jones, M. B., Cobb, B. A. Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.
Collapse
Affiliation(s)
- Douglas M. Oswald
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Edward S. Sim
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Courtney Baker
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Obada Farhan
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Sara M. Debanne
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Nathan J. Morris
- Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Benigno G. Rodriguez
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Mark B. Jones
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Brian A. Cobb
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| |
Collapse
|
|
18
|
Baldé A, Lang S, Wagner A, Ferrières J, Montaye M, Tattevin P, Cotte L, Aslangul E, Bidégain F, Chéret A, Mary-Krause M, Meynard JL, Molina JM, Partisani M, Roger PM, Boccara F, Costagliola D. Trends in the risk of myocardial infarction among HIV-1-infected individuals relative to the general population in France: Impact of gender and immune status. PLoS One 2019; 14:e0210253. [PMID: 30650119 PMCID: PMC6334967 DOI: 10.1371/journal.pone.0210253] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 12/19/2018] [Indexed: 02/07/2023] Open
Abstract
We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/μL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.
Collapse
Affiliation(s)
- Aliou Baldé
- Sorbonne Université, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Sylvie Lang
- Sorbonne Université, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Aline Wagner
- Laboratoire d'épidémiologie et de santé publique, Université de Strasbourg, Strasbourg, France
| | - Jean Ferrières
- Centre hospitalier universitaire de Rangueil, service de cardiologie B, Université de Toulouse, Toulouse, France
| | - Michèle Montaye
- INSERM, Institut Pasteur de Lille, Univ. Lille, CHU Lille, France
| | - Pierre Tattevin
- Hôpital Universitaire Pontchaillou, service des maladies infectieuses et USI, Rennes, France
| | - Laurent Cotte
- INSERM U1052, Hospices Civils de Lyon, Hôpital de la Croix Rousse, service des maladies infectieuses et tropicales, Lyon, France
| | - Elisabeth Aslangul
- Sorbonne Paris Cité, Université Paris Descartes, APHP, Hôtel Dieu, service de médecine interne, Paris, France
| | - Frédéric Bidégain
- APHP, Hôpital Avicenne, service de maladie infectieuse, Bobigny, France
| | - Antoine Chéret
- Sorbonne Paris Cité, Université Paris Descartes, Paris, Centre hospitalier de Tourcoing, service des maladies infectieuses, Tourcoing, France
| | - Murielle Mary-Krause
- Sorbonne Université, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Jean-Luc Meynard
- APHP, Hôpital Saint-Antoine, service des maladies infectieuses et tropicales, Paris, France
| | - Jean-Michel Molina
- Sorbonne Paris Cité, Université de Paris Diderot Paris, INSERM, UMRS 941, APHP, Hôpital Saint-Louis, service des maladies infectieuses et tropicales, Paris, France
| | - Marialuisa Partisani
- Hôpitaux Universitaires de Strasbourg, Le Trait D’Union, centre de soins de l’infection par le VIH, Strasbourg, France
| | - Pierre-Marie Roger
- Université de Nice Sophia-Antipolis, Centre hospitalier universitaire de Nice, groupe hospitalier l’Archet, service d’infectiologie, Nice, France
| | - Franck Boccara
- Sorbonne Université, INSERM, APHP, Hôpital Saint-Antoine, service de cardiologie, Paris, France
| | - Dominique Costagliola
- Sorbonne Université, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique, IPLESP, Paris, France
| |
Collapse
|
|
19
|
Opsomer M, Dimitrova D, Verspeelt J, Purrington A, Mehbob A, Chavers S, Pai H, Vanveggel S, Luo D, Brown K, Moecklinghoff C, Nettles RE, Boven K. Evaluation of Cardiovascular Disease Risk in HIV-1-Infected Patients Treated with Darunavir. Drugs R D 2018; 18:199-210. [PMID: 29992490 PMCID: PMC6131121 DOI: 10.1007/s40268-018-0238-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Introduction We evaluated cardiovascular disease (CVD) risk associated with darunavir treatment and examined the demographic/clinical characteristics of darunavir users based on data from Janssen-sponsored clinical trials, post-marketing pharmacovigilance databases, and administrative claims databases. Methods First, selected CVD events [myocardial infarction, stroke, sudden death, invasive cardiovascular procedures (coronary artery angioplasty or bypass, or carotid endarterectomy)] were analyzed in 19 Janssen-sponsored phase 2–4 studies (incidence rates estimated from pooled data; 95% confidence intervals derived from Poisson distribution). Second, analyses were conducted to identify spontaneously reported CVD events in post-marketing pharmacovigilance databases and evaluate disproportional reporting of CVD events for darunavir (using Empirical Bayesian Geometric Mean scores). Third, baseline demographic/clinical characteristics of human immunodeficiency virus-1 (HIV-1)–infected patients in general and new users of darunavir and atazanavir were explored using three US administrative claims databases. Results Among 19 Janssen-sponsored clinical trials (treatment durations ≤ 6 years), the CVD event rate (95% CI) per 1000 person-years (pooled population; n = 5713) was 6.15 (2.91–11.89), and was lower for patients who used once-daily darunavir/ritonavir 800/100 mg [0.71 (0.16–3.05); n = 1326] versus twice-daily darunavir/ritonavir 600/100 mg [9.21 (4.94–16.04); n = 3058]. Trend analysis of post-marketing pharmacovigilance data showed that cumulative CVD event reporting rates for darunavir users (any dose) generally declined over time. Spontaneously reported CVD events were not disproportionately reported with darunavir versus other protease inhibitors. Compared with the general HIV-1–infected population and atazanavir users, higher proportions of darunavir users were male, older, and had comorbidities associated with CVD risk based on results from US administrative claims databases. Conclusions This comprehensive review of Janssen-sponsored clinical trial, post-marketing, and epidemiological data does not suggest that CVD should be considered an important risk for users of darunavir. Electronic supplementary material The online version of this article (10.1007/s40268-018-0238-8) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
| | | | | | | | | | - Scott Chavers
- Janssen Research and Development, LLC, Titusville, NJ, USA
| | - Helen Pai
- Janssen Research and Development, LLC, Raritan, NJ, USA
| | | | - Donghan Luo
- Janssen Research and Development, LLC, Titusville, NJ, USA
| | | | | | | | - Katia Boven
- Janssen Research and Development, LLC, Titusville, NJ, USA
| |
Collapse
|
|
20
|
Stroke in HIV. Can J Cardiol 2018; 35:280-287. [PMID: 30825950 DOI: 10.1016/j.cjca.2018.11.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 11/21/2018] [Accepted: 11/30/2018] [Indexed: 12/26/2022] Open
Abstract
Stroke is a heterogeneous disease in persons living with human immunodeficiency virus (HIV). HIV is thought to increase the risk of stroke through both HIV-related and traditional stroke risk factors, which vary with respect to the patient's age and clinical characteristics. Numerous studies show that detectable viremia and immunosuppression increase the risk of stroke across all ages, whereas traditional risk factors are more common in the aging population with HIV. As persons living with HIV age and acquire traditional stroke risk factors, the prevalence of stroke will likely continue to increase. Large- and small-vessel disease are the most common causes of stroke, although it is important to evaluate for infectious etiology as well. Research regarding the management of stroke in patients with HIV is scant, and recommendations often parallel those for the general population. Treatment of HIV and effective reduction of traditional stroke risk factors is important to reduce the risk of stroke in persons living with HIV. Future research will help elucidate the pathophysiology of HIV and stroke risk, investigate sex differences in stroke risk, and evaluate the safety and benefits of standard stroke preventative measures and HIV-specific interventions in this population.
Collapse
|
|
21
|
Guaraldi G, Pintassilgo I, Milic J, Mussini C. Managing antiretroviral therapy in the elderly HIV patient. Expert Rev Clin Pharmacol 2018; 11:1171-1181. [PMID: 30444968 DOI: 10.1080/17512433.2018.1549484] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Owing to more effective and less toxic antiretroviral therapy (ART), people living with HIV (PLWH) live longer, a phenomenon expected to grow in the next decades. With advancing age, effectively treated PLWH experience not only a heightened risk for non-infective comorbidities and multimorbidity, but also for geriatric syndromes and frailty. In addition, older adults living with HIV (OALWH) have a higher prevalence of so-called iatrogenic triad described as polypharmacy (PP), potentially inappropriate medication use, and drug-drug interactions. Areas covered: This review will focus the management of ART in OALWH. We will discuss iatrogenic triad and best way to address PP. Special focus will be given to pharmacokinetic and pharmacodynamic aspects of ART in the elderly, evaluation of ART toxicities, and specific ART strategies commonly used in this population. Expert commentary: Research should be focused on recruiting more OALWH, frail individuals in particular, into the clinical trials and specific geriatric outcome need to be considered together with traditional viroimmunological outcomes.
Collapse
Affiliation(s)
- Giovanni Guaraldi
- a Modena HIV Metabolic Clinic , Azienda Policlinico-Universitaria di Modena , Modena , Italy.,b Department of Medical and Surgical Sciences for Children & Adults , University of Modena and Reggio Emilia , Modena , Italy
| | - Ines Pintassilgo
- c Internal Medicine Department , Hospital Garcia de Orta , Almada , Portugal
| | - Jovana Milic
- a Modena HIV Metabolic Clinic , Azienda Policlinico-Universitaria di Modena , Modena , Italy.,b Department of Medical and Surgical Sciences for Children & Adults , University of Modena and Reggio Emilia , Modena , Italy.,d Clinical and Experimental Medicine PhD Program , University of Modena and Reggio Emilia , Modena , Italy
| | - Cristina Mussini
- a Modena HIV Metabolic Clinic , Azienda Policlinico-Universitaria di Modena , Modena , Italy.,b Department of Medical and Surgical Sciences for Children & Adults , University of Modena and Reggio Emilia , Modena , Italy
| |
Collapse
|
|
22
|
Yanagawa B, Verma S, Dwivedi G, Ruel M. Cardiac Surgery in HIV Patients: State of the Art. Can J Cardiol 2018; 35:320-325. [PMID: 30744921 DOI: 10.1016/j.cjca.2018.11.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 11/12/2018] [Accepted: 11/13/2018] [Indexed: 11/27/2022] Open
Abstract
The clinical status of HIV infection has changed dramatically with the introduction of combined antiretroviral therapy. Patients with HIV are now living long enough to be susceptible to chronic illnesses, such as coronary disease and nonischemic cardiomyopathy, which can be consequences of the combined antiretroviral therapy treatment itself. Cardiovascular diseases are a major source of morbidity and mortality in HIV-positive patients. Increasingly, such patients might be candidates for the full range of cardiac surgical interventions, including coronary bypass, valve surgery, and heart transplantation. There has been a shift from offering palliative procedures such as pericardial window and balloon valvuloplasty, to more conventional and durable surgical therapies in HIV-positive patients. We herein provide an overview of the contemporary outcomes of cardiac surgery in this complex and unique patient population. We review some of the ethical issues around the selection and surgical care of HIV-positive patients. We also discuss strategies to best protect the surgical treatment team from the risks of HIV transmission. Finally, we highlight the need for involvement of dedicated infectious disease professionals in a multidisciplinary heart team approach, aiming at the comprehensive care of these unique and complex patients.
Collapse
Affiliation(s)
- Bobby Yanagawa
- Division of Cardiac Surgery, St Michael's Hospital, Toronto, Ontario, Canada.
| | - Subodh Verma
- Division of Cardiac Surgery, St Michael's Hospital, Toronto, Ontario, Canada
| | - Girish Dwivedi
- Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, Australia
| | - Marc Ruel
- Ottawa Heart Institute, University of Ottawa, Ottawa, Ontario, Canada
| |
Collapse
|
|
23
|
Churchill D, Waters L, Ahmed N, Angus B, Boffito M, Bower M, Dunn D, Edwards S, Emerson C, Fidler S, Fisher M, Horne R, Khoo S, Leen C, Mackie N, Marshall N, Monteiro F, Nelson M, Orkin C, Palfreeman A, Pett S, Phillips A, Post F, Pozniak A, Reeves I, Sabin C, Trevelion R, Walsh J, Wilkins E, Williams I, Winston A. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. HIV Med 2018; 17 Suppl 4:s2-s104. [PMID: 27568911 DOI: 10.1111/hiv.12426] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | | | | | - Mark Bower
- Chelsea and Westminster Hospital, London, UK
| | | | - Simon Edwards
- Central and North West London NHS Foundation Trust, UK
| | | | - Sarah Fidler
- Imperial College School of Medicine at St Mary's, London, UK
| | | | | | | | | | | | | | | | - Mark Nelson
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | | | | | | | | | - Anton Pozniak
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | - Caroline Sabin
- Royal Free and University College Medical School, London, UK
| | | | - John Walsh
- Imperial College Healthcare NHS Trust, London, UK
| | | | - Ian Williams
- Royal Free and University College Medical School, London, UK
| | | |
Collapse
|
|
24
|
Laurence J, Elhadad S, Ahamed J. HIV-associated cardiovascular disease: importance of platelet activation and cardiac fibrosis in the setting of specific antiretroviral therapies. Open Heart 2018; 5:e000823. [PMID: 30018781 PMCID: PMC6045710 DOI: 10.1136/openhrt-2018-000823] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 05/02/2018] [Accepted: 05/15/2018] [Indexed: 12/18/2022] Open
Abstract
HIV infection is a risk factor for cardiovascular disease (CVD). This risk is accentuated by certain combination antiretroviral therapies (cARTs), independent of their effects on lipid metabolism and insulin sensitivity. We sought to define potential mechanisms for this association through systematic review of clinical and preclinical studies of CVD in the setting of HIV/cART from the English language literature from 1989 to March 2018. We used PubMed, Web of Knowledge and Google Scholar, and conference abstracts for the years 2015-March 2018. We uncovered three themes: (1) a critical role for the HIV protease inhibitor (PI) ritonavir and certain other PI-based regimens. (2) The importance of platelet activation. Virtually all PIs, and one nucleoside reverse transcriptase inhibitor, abacavir, activate platelets, but a role for this phenomenon in clinical CVD risk may require additional postactivation processes, including: release of platelet transforming growth factor-β1; induction of oxidative stress with production of reactive oxygen species from vascular cells; suppression of extracellular matrix autophagy; and/or sustained proinflammatory signalling, leading to cardiac fibrosis and dysfunction. Cardiac fibrosis may underlie an apparent shift in the character of HIV-linked CVD over the past decade from primarily left ventricular systolic to diastolic dysfunction, possibly driven by cART. (3) Recognition of the need for novel interventions. Switching from cART regimens based on PIs to contemporary antiretroviral agents such as the integrase strand transfer inhibitors, which have not been linked to clinical CVD, may not mitigate CVD risk assumed under prior cART. In conclusion, attention to the effects of specific antiretroviral drugs on platelet activation and related profibrotic signalling pathways should help: guide selection of appropriate anti-HIV therapy; assist in evaluation of CVD risk related to novel antiretrovirals; and direct appropriate interventions.
Collapse
Affiliation(s)
- Jeffrey Laurence
- Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York City, New York, USA
| | - Sonia Elhadad
- Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York City, New York, USA
| | - Jasimuddin Ahamed
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
| |
Collapse
|
|
25
|
González-Cordón A, Doménech M, Camafort M, Martínez-Rebollar M, Torres B, Laguno M, Rojas J, Loncà M, Blanco JL, Mallolas J, Gatell JM, de Lazzari E, Martínez E. Subclinical cardiovascular disease in patients starting contemporary protease inhibitors. HIV Med 2018; 19:497-503. [PMID: 29745457 DOI: 10.1111/hiv.12619] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2018] [Indexed: 11/26/2022]
Abstract
OBJECTIVES The aim of the study was to assess changes in and factors associated with anatomical [carotid artery intima-media thickness (CIMT)] and functional (arterial stiffness) markers of subclinical cardiovascular disease progression in antiretroviral-naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors. METHODS This was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV-1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open-label clinical trial comparing the effects of ritonavir-boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral-naïve HIV-infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow-up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV-related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis. RESULTS Thirty-three patients were included in this pilot study. While CIMT significantly increased in the pooled population [median (interquartile range (IQR)) 68 (-13, 128) μm; P = 0.0511], AIx@75 did not [median (IQR) 1 (-6, 5)%; P = 0.8964]. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir [median change (IQR) 117 (-2, 143) vs. -6 (-58, 89) μm, respectively; P = 0.0917]. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval -1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor. CONCLUSIONS CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral-naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.
Collapse
Affiliation(s)
- A González-Cordón
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - M Doménech
- Cardiovascular, Nutrition and Aging Group, Hypertension and Vascular Risk Unit, Department of Internal Medicine, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - M Camafort
- Hypertension and Vascular Risk Unit, Department of Internal Medicine, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain
| | - M Martínez-Rebollar
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - B Torres
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - M Laguno
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - J Rojas
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - M Loncà
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - J L Blanco
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - J Mallolas
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - J M Gatell
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - E de Lazzari
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - E Martínez
- Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
| |
Collapse
|
|
26
|
Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV 2018; 5:e291-e300. [PMID: 29731407 DOI: 10.1016/s2352-3018(18)30043-2] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 03/04/2018] [Accepted: 03/12/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Although earlier protease inhibitors have been associated with increased risk of cardiovascular disease, whether this increased risk also applies to more contemporary protease inhibitors is unknown. We aimed to assess whether cumulative use of ritonavir-boosted atazanavir and ritonavir-boosted darunavir were associated with increased incidence of cardiovascular disease in people living with HIV. METHODS The prospective Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study consists of people living with HIV-1 from 11 cohorts in Australia, Europe, and the USA. Participants were monitored from Jan 1, 2009, until the earliest of a cardiovascular event, 6 months after the last visit, or until Feb 1, 2016. The outcome of interest was the incidence of cardiovascular disease in adults (aged ≥16 years) living with HIV who were being treated with contemporary treatments. We defined cardiovascular disease as centrally validated myocardial infarction, stroke, sudden cardiac death, or use of invasive cardiovascular procedures, including coronary bypass, coronary angioplasty, and carotid endarterectomy. We used Poisson regression models to assess the associations between cardiovascular disease and the contempoary protease inhibitors atazanavir and darunavir (both boosted with ritonavir). FINDINGS 49 709 participants were enrolled in the original cohort from 1999 onwards; 35 711 (71·8%) participants with available data on CD4 cell count and viral load at the 2009 baseline were included in the current analysis, and 13 998 (28·2%) participants had insufficent follow-up data after 2009. During a median 6·96 years of follow-up (IQR 6·28-7·08), 1157 people developed cardiovascular disease (incidence rate 5·34 events per 1000 person-years; 95% CI 5·03-5·65). The incidence rate of cardiovascular disease progressively increased from 4·91 events per 1000 person-years (4·59-5·23) in individuals unexposed to ritonavir-boosted darunavir to 13·67 events per 1000 person-years (8·51-18·82) in those exposed to the drug for more than 6 years. The changes associated with ritonavir-boosted atazanavir were less pronounced, showing an incidence rate of 5·03 cardiovascular events per 1000 person-years (4·69-5·37) in unexposed individuals to 6·68 events per 1000 person-years (5·02-8·35) in participants exposed for more than 6 years. After adjustment, keeping factors on the potential causal pathway from boosted protease inhibitor use to cardiovascular disease fixed at baseline, ritonavir-boosted darunavir use was associated with increased risk of cardiovascular disease (incidence rate ratio 1·59; 95% CI 1·33-1·91 per 5 years additional use), but use of ritonavir-boosted atazanavir was not (1·03; 0·90-1·18). This association remained after adjustment for time-updated factors on the potential causal pathway; myocardial infarction and stroke separately; plasma bilirubin concentration; and after stratification by use of ritonavir-boosted darunavir as the first ever protease inhibitor, used in combination with a non-nucleoside reverse transcriptase inhibitor, by previous virological failure, and by those at high risk of cardiovascular disease. INTERPRETATION Cumulative use of ritonavir-boosted darunavir, but not of ritonavir-boosted atazanavir, is associated with progressively increasing risk of cardiovascular disease. Causal inference is limited by the observational nature of the D:A:D study. Our findings should prompt investigation into the possible underlying mechanisms of this finding. FUNDING The Highly Active Antiretroviral Therapy Oversight Committee.
Collapse
|
|
27
|
Kaplan-Lewis E, Aberg JA, Lee M. Atherosclerotic Cardiovascular Disease and Anti-Retroviral Therapy. Curr HIV/AIDS Rep 2017; 13:297-308. [PMID: 27562769 DOI: 10.1007/s11904-016-0331-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
In the current era of available therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) nears that of the general population. Atherosclerotic cardiovascular disease (ASCVD) has become a particular burden for PLWH and society at large. PLWH have historically been shown to have an excess of cardiovascular risk and subsequent events when compared to the general population. Potential explanations include the increased prevalence of traditional risk factors, direct inflammatory and immunological effects from the HIV virus itself, and metabolic adverse effects of anti-retroviral therapy (ART). Over the past few years, there has been building evidence that chronic inflammation and immune activation independent of virologic suppression contribute significantly to excess ASCVD risk. Although independent agents and combination therapies have varying metabolic effects, the evidence from major randomized controlled trials (RCTs) supports the benefits of early initiation of ART. In this review, we will discuss the epidemiology of ASCVD in HIV-infected patients compared with the general population, give an overview of potential pathogenesis of high-risk plaque in HIV-infected patients, discuss different metabolic effects of individual anti-retrovirals, and discuss the limitations in current screening models for assessing cardiovascular disease (CVD) risk and future directions for treatment.
Collapse
Affiliation(s)
- Emma Kaplan-Lewis
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA
| | - Judith A Aberg
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA
| | - Mikyung Lee
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA.
| |
Collapse
|
|
28
|
Escota GV, O'Halloran JA, Powderly WG, Presti RM. Understanding mechanisms to promote successful aging in persons living with HIV. Int J Infect Dis 2017; 66:56-64. [PMID: 29154830 DOI: 10.1016/j.ijid.2017.11.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 10/26/2017] [Accepted: 11/03/2017] [Indexed: 01/05/2023] Open
Abstract
The mortality rate associated with HIV infection plummeted after the introduction of effective antiretroviral therapy pioneered two decades ago. As a result, HIV-infected people now have life expectancies comparable to that of HIV-uninfected individuals. Despite this, increased rates of osteoporosis, chronic liver disease, and in particular cardiovascular disease have been reported among people living with HIV infection. With the aging HIV-infected population, the burden of these comorbid illnesses may continue to accrue over time. In this paper, we present an overview of the aging HIV-infected population, its epidemiology and the many challenges faced. How to define and measure successful aging will also be reviewed. Finally, opportunities that may help mitigate the challenges identified and ensure successful aging among people living with HIV infection will be examined.
Collapse
Affiliation(s)
- Gerome V Escota
- Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, USA.
| | - Jane A O'Halloran
- Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, USA
| | - William G Powderly
- Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, USA
| | - Rachel M Presti
- Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, USA
| |
Collapse
|
|
29
|
Abstract
Infection with the human immunodeficiency virus (HIV), and subsequent treatment with antiretroviral therapy (ART), is often associated with perturbations in lipid profiles. Furthermore, persistent inflammation, in spite of suppression of viral replication by ART, likely contributes to modifications in lipid composition and function, exacerbating risk for development of cardiovascular disease (CVD). Increased levels of several pro-inflammatory lipid species, including oxidized low-density lipoprotein (LDL) and high-density lipoprotein (HDL), have been measured in HIV-infected persons and are associated with markers of immune activation. The mechanisms linked to this bidirectional relationship in which inflammation increases lipid levels and promotes their modification, and these modified lipid species perpetuate inflammatory processes, require further investigation. Treatment with statins and other lifestyle modifications, including improvement in dietary intake and exercise, are critical to reducing CVD risk. Well-designed clinical trials that take into account the complex relationships among lipids and inflammation within persons infected with HIV need to be considered.
Collapse
Affiliation(s)
- Nicholas T Funderburg
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, 453 W. 10th Ave., 535A Atwell Hall, Columbus, OH, 43210, USA
| | - Nehal N Mehta
- Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, Bethesda, MD, 20892, USA.
| |
Collapse
|
|
30
|
Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir. PLoS One 2017; 12:e0181993. [PMID: 29023508 PMCID: PMC5638209 DOI: 10.1371/journal.pone.0181993] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 07/06/2017] [Indexed: 12/29/2022] Open
Abstract
Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries. Trial registration: ClinicalTrials.gov NCT03019783.
Collapse
|
|
31
|
LaFleur J, Bress AP, Rosenblatt L, Crook J, Sax PE, Myers J, Ritchings C. Cardiovascular outcomes among HIV-infected veterans receiving atazanavir. AIDS 2017; 31:2095-2106. [PMID: 28692532 PMCID: PMC5603981 DOI: 10.1097/qad.0000000000001594] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 06/27/2017] [Accepted: 06/27/2017] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown. DESIGN Population-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015. SETTING Veterans Health Administration hospitals and clinics throughout the United States. PARTICIPANTS Treatment-naive patients with HIV infection (N = 9500). ANTIRETROVIRAL EXPOSURES Initiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs). MAIN OUTCOME/EFFECT SIZE MEASURES Incidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting. RESULTS Incidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively. CONCLUSION Among treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.
Collapse
Affiliation(s)
- Joanne LaFleur
- Department of Pharmacotherapy, University of Utah College of Pharmacy
- Informatics, Decision-Enhancement, and Surveillance (IDEAS) Center, Salt Lake City VA Health Care System
| | - Adam P. Bress
- Informatics, Decision-Enhancement, and Surveillance (IDEAS) Center, Salt Lake City VA Health Care System
- Department of Population Health Sciences, University of Utah, Salt Lake City, Utah
| | | | - Jacob Crook
- Informatics, Decision-Enhancement, and Surveillance (IDEAS) Center, Salt Lake City VA Health Care System
- Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah
| | - Paul E. Sax
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Joel Myers
- Bristol-Myers Squibb, Lawrenceville, New Jersey
| | | |
Collapse
|
|
32
|
Bijker R, Choi JY, Ditangco R, Kiertiburanakul S, Lee MP, Siwamogsatham S, Pujari S, Ross J, Wong CY, Wong WW, Yunihastuti E, Law M. Cardiovascular Disease and Cardiovascular Disease Risk in HIV-Positive Populations in the Asian Region. Open AIDS J 2017; 11:52-66. [PMID: 29302277 PMCID: PMC5753029 DOI: 10.2174/1874613601711010052] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 07/03/2017] [Accepted: 07/20/2017] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Cardiovascular diseases (CVD) are becoming more prevalent in HIV-infected populations as they age largely due to improved treatment outcomes. Assessment of CVD risk and CVD risk factors in HIV-positive populations has focused on high income settings, while there are limited studies evaluating CVD in HIV-positive populations in the Asian region. MATERIALS AND METHODS We provided an overview of the prevalence and incidence of CVD and its risk factors in adult HIV-positive populations, and of the strategies currently in place for CVD management in the Asian region. RESULTS Studies from the Asian region showed that CVD and CVD risk factors, such as dyslipidaemia, elevated blood glucose, obesity and smoking, are highly prevalent in HIV-positive populations. A number of studies suggested that HIV infection and antiretroviral therapy may contribute to increased CVD risk. National HIV treatment guidelines provide some directions regarding CVD risk prevention and management in the HIV-infected population, however, they are limited in number and scope. CONCLUSION Development and consolidation of guidelines for integrated CVD and HIV care are essential to control the burden of CVD in HIV-positive populations. To inform guidelines, policies and practice in the Asian region, research should focus on exploring appropriate CVD risk screening strategies and estimating current and future CVD mortality and morbidity rates.
Collapse
Affiliation(s)
- Rimke Bijker
- The Kirby Institute, UNSW, Sydney, NSW 2052, Australia
| | - Jun Yong Choi
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | | | | | - Man Po Lee
- Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Sarawut Siwamogsatham
- King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | - Matthew Law
- The Kirby Institute, UNSW, Sydney, NSW 2052, Australia
| |
Collapse
|
|
33
|
Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers, and Cerebrovascular Endothelial Function Among Adults in Urban China. J Acquir Immune Defic Syndr 2017; 74:339-346. [PMID: 27875362 DOI: 10.1097/qai.0000000000001254] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. METHODS We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. RESULTS In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. CONCLUSIONS Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.
Collapse
|
|
34
|
Abstract
INTRODUCTION During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of protease inhibitor allows a higher genetic barrier, as few or no drug-resistant mutations are detected in patients with virologic failure. Areas covered: Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV) as a pharmacoenhancer of ATV was established. Additionally, randomized clinical trials demonstrated that ATV/c and ATV/ritonavir had comparable efficacy and safety profiles. Low rates of virologic failure and no ATV resistance mutations were observed in these clinical trials. Therefore, COBI shows increased advantages over RTV, such as no activity against HIV, fewer drug-drug interactions and better solubility, which promotes coformulation strategies with less pill burden, better tolerability, and, potentially, higher life-long treatment adherence. Expert commentary: ATV/c regimen supports its useas an effective treatment option for HIV-1 infected patients with increased cardiovascular disease and chronic kidney disease risk associated with aging. In addition, ATV/c is a new opportunity to expand the strategy of switch to a dual therapy to lower the risk of long-term toxicities as well as the advantage of its cost-benefit.
Collapse
Affiliation(s)
- Francisco Antunes
- a Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa , Lisboa , Portugal
| |
Collapse
|
|
35
|
Volpe M, Uglietti A, Castagna A, Mussini C, Marchetti G, Bellagamba R, Bini T, Mancusi D, Termini R. Cardiovascular disease in women with HIV-1 infection. Int J Cardiol 2017; 241:50-56. [PMID: 28285796 DOI: 10.1016/j.ijcard.2017.02.117] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Revised: 01/30/2017] [Accepted: 02/24/2017] [Indexed: 12/14/2022]
Abstract
Cardiovascular disease is a leading cause of death in women, nevertheless it is often underestimated in female patients without overt risk factors. The chronic infection by Human Immunodeficiency Virus (HIV) is clearly associated, along with the use of certain antiretroviral drugs and traditional risk factors, with an increased risk of cardiovascular diseases. The aim of this manuscript is to review the epidemiology, risk factors, pathogenesis, diagnostic approach, primary and secondary prevention strategies of cardiovascular disease in HIV-negative and HIV-positive female subjects. The ultimate goal is to promote knowledge and development of specific and appropriate clinical interventions and guidelines in this group of high-risk patients, mostly in view of the expected growth of ageing females with HIV.
Collapse
Affiliation(s)
- Massimo Volpe
- Cardiology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, University of Rome Sapienza, Italy; IRCCS Neuromed, IS, Italy.
| | | | | | - Cristina Mussini
- Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Marchetti
- Department of Health Sciences, Clinic of Infectious Diseases, University of Milan, ASST Santi Paolo and Carlo, Milan, Italy
| | | | - Teresa Bini
- Department of Health Sciences, Clinic of Infectious Diseases, University of Milan, ASST Santi Paolo and Carlo, Milan, Italy
| | | | | |
Collapse
|
|
36
|
Abstract
While mortality rates related to cardiovascular disease (CVD) have decreased over time among adults with HIV, excess risk of CVD in the HIV-infected population may persist despite highly active antiretroviral therapy (HAART) treatment and aggressive CVD risk factor control. Beyond atherosclerotic CVD, recent studies suggest that HIV infection may be associated with left ventricular systolic and diastolic function, interstitial myocardial fibrosis, and increased cardiac fat infiltration. Thus, with the increasing average age of the HIV-infected population, heart failure and arrhythmic disorders may soon rival coronary artery disease as the most prevalent forms of CVD. Finally, the question of whether HIV infection should be considered in clinical risk stratification has never been resolved, and this question has assumed new importance with recent changes to lipid treatment guidelines for prevention of CVD.
Collapse
|
|
37
|
Randell P, Jackson A, Milinkovic A, Boffito M, Moyle G. An open-label, randomized study of the impact on insulin sensitivity, lipid profile and vascular inflammation by treatment with lopinavir/ritonavir or raltegravir in HIV-negative male volunteers. Antivir Ther 2016; 22:145-151. [PMID: 27708251 DOI: 10.3851/imp3098] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/21/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND We aimed to measure the effect of raltegravir (RAL) on insulin sensitivity and surrogates of cardiovascular risk in healthy HIV-seronegative volunteers compared to that of lopinavir/r (LPV/r), a positive control. METHODS An open-label, two phase crossover study in HIV-negative male subjects randomized 1:1 to receive either 2 weeks of LPV/r followed by a 2-week washout period and 2 weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week dosing phase. Fasting samples for lipids, adiponectin, leptin, vascular inflammatory biomarkers and CD36 were also taken. RESULTS A total of 16 subjects completed the study. At the baseline visit the mean insulin-stimulated glucose disposal per unit insulin (M/I) was 7.97 and 8.30 for LPV/r and RAL, respectively. The mean (sem) percentage change from baseline was -16.10% (3.84) after 2 weeks of LPV/r and -0.43% (4.83) after 2 weeks of RAL. Absolute M/I was 25% lower for LPV/r than for RAL (P=0.001). Triglycerides and total cholesterol rose significantly with LPV/r (+0.5 mmol/l, P=0.002 and +0.4 mmol/l, P<0.0001), but were unchanged with RAL. Proathrogenic lipid subfractions of low-density lipoprotein (LDL) cholesterol increased with LPV/r and were unaffected with RAL. LDL peak and mean particle diameter and LDL I significantly decreased with LPV/r (P<0.05), and trend of increased LDL III was detected. High-sensitivity C-reactive protein declined with RAL (-0.2 mg/l, P=0.043) but was elevated after LPV/r (+0.25 mg/l, P=0.03). CONCLUSIONS RAL was not associated with measurable change in glycaemic, metabolic or inflammatory effects.
Collapse
Affiliation(s)
- Paul Randell
- St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK
| | - Akil Jackson
- St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.,Present: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.,Present: Gilead Sciences Ltd., London, UK
| | - Ana Milinkovic
- St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.,Present: Research Department of Infection and Population Health, University College London, London, UK
| | - Marta Boffito
- St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK
| | - Graeme Moyle
- St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK
| |
Collapse
|
|
38
|
Abstract
PURPOSE OF REVIEW To evaluate evidence that statins reduce cardiovascular risk in patients living with HIV. RECENT FINDINGS Moderate to high-dose atorvastatin and rosuvastatin appear to reduce noncalcified coronary plaque volume and slow progression of carotid intima-media thickness in patients with treated HIV infection. Expected lipoprotein changes with statins on the background of modern antiretroviral therapy are similar to the general population. In addition to lipids, the statin benefit may be mediated in part by improvements in vascular inflammation and levels of T-cell and monocyte activation. One concern is the potential for rosuvastatin to cause insulin resistance. Decisions to prescribe statins must be done in the context of global risk assessment, but traditional risk calculators such as the Framingham Risk Score or the American College of Cardiology/American Heart Association pooled-risk equations underestimate risk in this population. Furthermore, many patients with subclinical disease would not be recommended for statins according to the most recent American College of Cardiology/American Heart Association guidelines. SUMMARY Statins are likely to improve cardiovascular outcomes for patients with HIV, but results of the first outcome study are not expected until 2020. In the meantime, clinicians should individualize statin prescriptions, and should consider using more potent statins (rosuvastatin, atorvastatin, and pitavastatin) when possible.
Collapse
|
|
39
|
Chow D, Shikuma C, Ritchings C, Guo M, Rosenblatt L. Atazanavir and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Patients: A Systematic Review. Infect Dis Ther 2016; 5:473-489. [PMID: 27677263 PMCID: PMC5125135 DOI: 10.1007/s40121-016-0132-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Indexed: 12/15/2022] Open
Abstract
Introduction Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular disease (CVD). While viral suppression with antiretroviral therapy decreases CVD risk overall, several studies have suggested that certain antiretrovirals, particularly certain protease inhibitors, may be associated with an increased relative risk of CVD. In AIDS Clinical Trials Group 5260 s, ritonavir-boosted atazanavir (ATV) was associated with slower atherosclerosis progression compared to ritonavir-boosted darunavir and raltegravir, potentially due to hyperbilirubinemia. Although hyperbilirubinemia may lead to increased rates of treatment discontinuation, it may also contribute to a favorable cardiovascular (CV) profile for ATV. To fully elucidate the effect of ATV on CVD risk among HIV-infected patients, a systematic review of the literature was performed. Methods A systematic search of the PubMed and Embase databases was conducted on August 26, 2015, using terms to identify papers that discuss ATV, HIV, and CVD. Articles were limited to English-language publications of randomized-controlled or observational studies investigating adult humans. The primary outcome was the incidence of CVD. Articles describing surrogate markers of CVD were also included. Results Ten studies were included in this qualitative analysis: six reported CVD outcomes, two reported data on atherosclerosis as assessed by carotid intima-media thickness (cIMT), and two reported outcomes related to endothelial function. The studies reporting the incidence of myocardial infarction (MI) among HIV-infected patients showed that ATV (boosted and unboosted) was not associated with an increased risk of acute MI. Other CV endpoints were similarly unaffected by treatment with ATV. Compared with non-ATV-based regimens, ATV had beneficial effects on cIMT progression in the publications identified, with no apparent impact on endothelial function. Conclusions This analysis showed that there was no increased risk or occurrence of adverse CV events among HIV-infected patients receiving ATV. Markers of atherosclerosis were improved, suggesting a possible antioxidant effect of ATV, and endothelial function was not affected. Funding Bristol-Myers Squibb (article processing charges and medical writing support). Electronic supplementary material The online version of this article (doi:10.1007/s40121-016-0132-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Dominic Chow
- Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii Mānoa, Honolulu, HI, USA.
| | - Cecilia Shikuma
- Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii Mānoa, Honolulu, HI, USA
| | | | - Muxing Guo
- Bristol-Myers Squibb, Plainsboro, NJ, USA
| | | |
Collapse
|
|
40
|
Risk of cardiovascular events among patients with HIV treated with atazanavir-containing regimens: a retrospective cohort study. BMC Infect Dis 2016; 16:492. [PMID: 27643691 PMCID: PMC5028993 DOI: 10.1186/s12879-016-1827-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 09/09/2016] [Indexed: 11/10/2022] Open
Abstract
Background A previous cohort study indicated that atazanavir (ATV), a protease inhibitor used for HIV treatment, is not associated with an increased risk of cardiovascular (CV) events. The objective of this study was to compare the risk of CV events among antiretroviral-naïve patients initiating ATV-containing versus ATV-free ARV regimens. Methods Patients with HIV who newly initiated antiretroviral therapy were selected from MarketScan Commercial and Multi-State Medicaid databases. The first claim for an antiretroviral medication between 1/1/2007 and 12/31/2013 was known as the index date. Patients were categorized as initiating an ATV-containing or an ATV-free regimen. Patients who did not have 6 months of continuous enrollment prior to the index date or who had evidence of a CV event during this time period were excluded. Myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass graft were identified through diagnosis and procedure codes. Patients were followed from index date until a CV event, continuous gap of >30 days without initiated ARV, a claim for ATV in the ATV-free cohort, disenrollment, or study end, whichever occurred first. Unadjusted incidence rates (IR) were calculated and propensity-score-weighted Cox proportional hazards models were fit to compare hazards of CV events between the two cohorts. Results A total of 22,211 patients (2437 ATV-containing and 19,774 ATV-free) were identified in the Commercial Database and 7136 patients were identified (1505 ATV-containing and 5631 ATV-free) in the Medicaid Database. CV events were uncommon (Commercial IR per 1000 person-years for a CV event: ATV-containing = 3.01, ATV-free = 3.26; Medicaid IR: ATV-containing = 10.9, ATV-free = 9.9). In propensity-score-weighted models combining the two populations, there was no significant difference in the hazards of a CV event for patients initiating an ATV-containing regimen compared with those initiating an ATV-free regimen (hazard ratio = 1.16, 95 % confidence interval 0.67–1.99). Conclusions In this real-world analysis, there was no significant increase in the risk of CV events associated with exposure to ATV-containing regimens. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1827-1) contains supplementary material, which is available to authorized users.
Collapse
|
|
41
|
Martin-Iguacel R, Llibre JM, Friis-Moller N. Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now? Curr HIV/AIDS Rep 2016; 12:375-87. [PMID: 26423407 DOI: 10.1007/s11904-015-0284-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population. The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking), toxicities associated with cumulative exposure to some antiretroviral agents, together with persistent chronic inflammation, and immune activation associated with HIV infection. Tools are available to calculate an individual's predicted risk of CVD and should be incorporated in the regular follow-up of HIV-infected patients. Targeted interventions to reduce this risk must be recommended, including life-style changes and medical interventions that might include changes in antiretroviral therapy.
Collapse
Affiliation(s)
- R Martin-Iguacel
- Infectious Diseases Department, Odense University Hospital, Søndre Boulevard 29, 5000, Odense C, Denmark.
| | - J M Llibre
- HIV Unit and "Lluita contra la SIDA" Foundation, Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona, Spain.
- Universitat Autònoma de Barcelona, Barcelona, Spain.
| | - N Friis-Moller
- Infectious Diseases Department, Odense University Hospital, Søndre Boulevard 29, 5000, Odense C, Denmark.
| |
Collapse
|
|
42
|
Burrowes S, Cahill P, Kottilil S, Bagchi S. Contribution of antiretroviral therapy to cardiovascular disease risk in HIV-infected patients. Future Virol 2016. [DOI: 10.2217/fvl-2016-0047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Rates of cardiovascular disease (CVD) are over twice as high in HIV-infected compared with uninfected patients, and this excess risk could be due to the effect of antiretroviral medications (ARVs) but the data regarding this are mixed. We described the literature on associations reported between classes and individual ARVs and rates of CVD and to changes in surrogate markers of subclinical CVD. Many PIs and certain NRTIs contribute to the development of CVD though recent generations of PIs appear to have less effect on development of CVD as assessed by surrogate measures of subclinical CVD. Future antiretroviral drug development efforts should include surrogate measures of subclinical cardiovascular to minimize the potential contributions of new ARVs to subclinical or clinical CVD.
Collapse
Affiliation(s)
- Shana Burrowes
- Department of Epidemiology & Human Genetics, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Patrick Cahill
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shyamasundaran Kottilil
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shashwatee Bagchi
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
43
|
Nou E, Lo J, Hadigan C, Grinspoon SK. Pathophysiology and management of cardiovascular disease in patients with HIV. Lancet Diabetes Endocrinol 2016; 4:598-610. [PMID: 26873066 PMCID: PMC4921313 DOI: 10.1016/s2213-8587(15)00388-5] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 10/05/2015] [Accepted: 10/07/2015] [Indexed: 12/15/2022]
Abstract
Results from several studies have suggested that people with HIV have an increased risk of cardiovascular disease, especially coronary heart disease, compared with people not infected with HIV. People living with HIV have an increased prevalence of traditional cardiovascular disease risk factors, and HIV-specific mechanisms such as immune activation. Although older, more metabolically harmful antiretroviral regimens probably contributed to the risk of cardiovascular disease, new data suggest that early and continuous use of modern regimens, which might have fewer metabolic effects, minimises the risk of myocardial infarction by maintaining viral suppression and decreasing immune activation. Even with antiretroviral therapy, however, immune activation persists in people with HIV and could contribute to accelerated atherosclerosis, especially of coronary lesions that are susceptible to rupture. Therefore, treatments that safely reduce inflammation in people with HIV could provide additional cardiovascular protection alongside treatment of both traditional and non-traditional risk factors.
Collapse
Affiliation(s)
- Eric Nou
- Program in Nutritional Metabolism, Massachusetts General Hospital, Boston, MA, USA
| | - Janet Lo
- Program in Nutritional Metabolism, Massachusetts General Hospital, Boston, MA, USA
| | - Colleen Hadigan
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Steven K Grinspoon
- Program in Nutritional Metabolism, Massachusetts General Hospital, Boston, MA, USA.
| |
Collapse
|
|
44
|
Abstract
Cardiovascular disease is one of the leading causes of morbidity and mortality in people living with HIV. Several epidemiological studies have shown an increased risk of myocardial infarction and stroke compared to uninfected controls. Although traditional risk factors contribute to this increased risk of cardiovascular disease, HIV-specific mechanisms likely also play a role. Systemic inflammation has been linked to cardiovascular disease in several populations suffering from chronic inflammation, including people living with HIV. Although antiretroviral therapy reduces immune activation, levels of inflammatory markers remain elevated compared to uninfected controls. The causes of this sustained immune response are likely multifactorial and incompletely understood. In this review, we summarize the evidence describing the relationship between inflammation and cardiovascular disease and discuss potential anti-inflammatory treatment options for cardiometabolic disease in people living with HIV.
Collapse
|
|
45
|
Trevillyan JM, Hoy JF. Managing Cardiovascular Risk in People Living with HIV. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2016. [DOI: 10.1007/s40506-016-0071-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
46
|
Martin-Iguacel R, Negredo E, Peck R, Friis-Møller N. Hypertension Is a Key Feature of the Metabolic Syndrome in Subjects Aging with HIV. Curr Hypertens Rep 2016; 18:46. [PMID: 27131801 PMCID: PMC5546311 DOI: 10.1007/s11906-016-0656-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
With widespread and effective antiretroviral therapy, the life expectancy in the HIV population has dramatically improved over the last two decades. Consequently, as patients are aging with HIV, other age-related comorbidities, such as metabolic disturbances and cardiovascular disease (CVD), have emerged as important causes of morbidity and mortality. An overrepresentation of traditional cardiovascular risk factors (RF), toxicities associated with long exposure to antiretroviral therapy, together with residual chronic inflammation and immune activation associated with HIV infection are thought to predispose to these metabolic complications and to the excess risk of CVD observed in the HIV population. The metabolic syndrome (MS) represents a clustering of RF for CVD that includes abdominal obesity, hypertension, dyslipidemia and insulin resistance. Hypertension is a prevalent feature of the MS in HIV, in particular in the aging population, and constitutes an important RF for CVD. Physicians should screen their patients for metabolic and cardiovascular risk at the regular visits to reduce MS and the associated CVD risk among people aging with HIV, since many of RF are under-diagnosed and under-treated conditions. Interventions to reduce these RF can include lifestyle changes and pharmacological interventions such as antihypertensive and lipid-lowering therapy, and treatment of glucose metabolism disturbances. Changes in antiretroviral therapy to more metabolic neutral antiretroviral drugs may also be considered.
Collapse
Affiliation(s)
- Raquel Martin-Iguacel
- Infectious Diseases Department, Odense University Hospital, Sdr Boulevard 29, 5000, Odense C, Denmark.
| | - Eugènia Negredo
- "Lluita contra la SIDA" Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
- Universitat de Vic-Universitat Central de Catalunya, Barcelona, Spain
| | - Robert Peck
- Department of Internal Medicine, Weill Bugando School of Medicine, PO Box 5034, Mwanza, Tanzania
- Center for Global Health, Weill Cornell Medical College, New York, NY, USA
| | - Nina Friis-Møller
- Infectious Diseases Department, Odense University Hospital, Sdr Boulevard 29, 5000, Odense C, Denmark
| |
Collapse
|
|
47
|
Scott J, Goetz MB. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults. Clin Geriatr Med 2016; 32:571-83. [PMID: 27394024 DOI: 10.1016/j.cger.2016.02.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.
Collapse
Affiliation(s)
- Jake Scott
- Infectious Diseases Section, Department of Medicine, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA
| | - Matthew Bidwell Goetz
- Infectious Diseases Section, Department of Medicine, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
| |
Collapse
|
|
48
|
Lee FJ, Monteiro P, Baker D, Bloch M, Roth N, Finlayson R, Moore R, Hoy J, Martinez E, Carr A. Rosuvastatin vs. protease inhibitor switching for hypercholesterolaemia: a randomized trial. HIV Med 2016; 17:605-14. [PMID: 26987376 DOI: 10.1111/hiv.12362] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2015] [Indexed: 11/29/2022]
Abstract
OBJECTIVES The aim of the study was to compare the efficacy and safety of rosuvastatin initiation with those of switching of ritonavir-boosted protease inhibitors (PI/rs) in HIV-1-infected adults with hypercholesterolaemia and increased cardiovascular risk scores. METHODS In this open-label, multicentre study, HIV-1-infected adults on PI/r-based therapy with viral load < 50 HIV-1 RNA copies/mL, fasting total cholesterol ≥ 5.5 mmol/L (both for ≥ 6 months) and elevated cardiovascular risk (Framingham score ≥ 8% or diabetes or family history), and not on lipid-lowering therapy, were randomized to open-label rosuvastatin 10 mg/day or to PI/r switching, both with standardized diet/exercise advice. The primary endpoint was change in total cholesterol at week 12 (intention to treat). RESULTS There were 43 participants (23 on rosuvastatin). Baseline characteristics were: mean [± standard deviation (SD)] age 55 (8.5) years, 42 (98%) male, 41 (95%) white race, and mean (± SD) total cholesterol 6.2 (1.2) mmol/L. At enrolment, PI/rs were lopinavir/ritonavir (n = 22; 51%), atazanavir/ritonavir (n = 12; 28%) and darunavir/ritonavir (n = 9; 21%). The commonest PI/r substitutes were raltegravir (n = 9; 45%) and rilpivirine (n = 4; 20%). All participants were adherent through to week 12. Rosuvastatin yielded greater declines than PI/r switching in total (- 21.4% vs. - 8.7%, respectively; P = 0.003) and low-density lipoprotein (- 29.9% vs. - 1.0%, respectively; P < 0.001) cholesterol, but smaller declines in very low-density lipoprotein cholesterol and triglycerides (P < 0.01). Cholesterol lowering was greater in participants on atazanavir/ritonavir or once-daily darunavir/ritonavir (vs. lopinavir/ritonavir). More study drug-related adverse events (mostly grade 1 nausea/diarrhoea; 10 vs. one, respectively; P = 0.001) occurred with PI/r switching than with rosuvastatin. CONCLUSIONS In adults receiving a PI/r, rosuvastatin 10 mg/day for 12 weeks yielded larger decreases in total and low-density lipoprotein cholesterol than PI/r switching, and was better tolerated.
Collapse
Affiliation(s)
- F J Lee
- Clinical Research Program, Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - P Monteiro
- Infectious Diseases Unit, Hospital Cliníc, University of Barcelona, Barcelona, Spain
| | - D Baker
- East Sydney Doctors, Sydney, NSW, Australia
| | - M Bloch
- Holdsworth House Medical Practice, Sydney, NSW, Australia
| | - N Roth
- Prahran Market Clinic, Melbourne, Vic., Australia
| | - R Finlayson
- Taylor Square Private Clinic, Sydney, NSW, Australia
| | - R Moore
- Northside Clinic, Melbourne, Vic., Australia
| | - J Hoy
- Department of Infectious Diseases, The Alfred Hospital & Monash University, Melbourne, Vic., Australia
| | - E Martinez
- Infectious Diseases Unit, Hospital Cliníc, University of Barcelona, Barcelona, Spain
| | - A Carr
- Clinical Research Program, Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia
| |
Collapse
|
|
49
|
Estrada V, Monge S, Gómez-Garre MD, Sobrino P, Masiá M, Berenguer J, Portilla J, Viladés C, Martínez E, Blanco JR. Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy. HIV Med 2016; 17:653-61. [PMID: 26935006 DOI: 10.1111/hiv.12368] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). METHODS A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. RESULTS After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. CONCLUSIONS When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
Collapse
Affiliation(s)
- V Estrada
- Hospital Clínico San Carlos-IdiSSC, Universidad Complutense, Madrid, Spain
| | - S Monge
- Universidad de Alcalá de Henares, CIBERESP, Spain
| | - M D Gómez-Garre
- Hospital Clínico San Carlos-IdiSSC, Universidad Complutense, Madrid, Spain
| | - P Sobrino
- Universidad de Alcalá de Henares, CIBERESP, Spain
| | - M Masiá
- Hospital General de Elche, Elche, Spain
| | - J Berenguer
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - J Portilla
- Hospital General Universitario de Alicante, Alicante, Spain
| | - C Viladés
- Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain
| | | | - J R Blanco
- Hospital San Pedro-CIBIR, Logroño, Spain
| | | |
Collapse
|
|
50
|
LMNA mutations resulting in lipodystrophy and HIV protease inhibitors trigger vascular smooth muscle cell senescence and calcification: Role of ZMPSTE24 downregulation. Atherosclerosis 2016; 245:200-11. [DOI: 10.1016/j.atherosclerosis.2015.12.012] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 11/21/2015] [Accepted: 12/07/2015] [Indexed: 11/23/2022]
|