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Dos Santos DM, Penteado JO, Nader MM, Basso RP, da Silva NMO, Quiche LCP, Borges MP, Gehres LFS, Hoffmann T, Rodrigues LF, da Silva Júnior FMR. Analysis of noninvasive methods in chronic hepatitis/human immunodeficiency virus mono- and co-infected patients with advanced fibrosis. Eur J Gastroenterol Hepatol 2025; 37:638-643. [PMID: 39976004 DOI: 10.1097/meg.0000000000002936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
OBJECTIVES The aim of this study was to evaluate the degree of advanced fibrosis (F3/F4) using noninvasive methods [elastography, Fibrosis-4 (FIB4), and aspartate aminotransferase to platelet ratio index (APRI)] before and after treatment with new direct-acting antiviral agents (DAAs) in patients with hepatitis C virus (HCV), both in cases of co-infection (HCV/HIV) and single infection (HCV). METHODS This is a longitudinal study involving patients with HCV who are co-infected with HIV, who initiated HCV treatment between a positive anti-HCV test for more than 6 months and detectable HCV RNA. The control group consisted of patients with HCV infection without HIV co-infection, who received treatment during the same period as the co-infected patients. RESULTS A total of 75 co-infected and 87 mono-infected HCV patients were eligible. Before treatment, elastography and FIB4 methods showed a strong agreement (0.73), while after treatment, the agreement was moderate (0.58). Between elastography and APRI, a strong agreement was observed before treatment (0.66) and fair/weak agreement after treatment (0.30). Both FIB4 and APRI showed perfect agreement at both time points with values above 0.9 (0.97 for pretreatment and 0.92 for posttreatment). The use of DAAs was associated with high rates of sustained virological response and reduction in fibrosis degrees in the posttreatment period, as assessed through biomarkers and hepatic elastography. CONCLUSION The utilization of biomarkers in clinical practice for assessing hepatic fibrosis is an essential tool. Thus, for an accurate evaluation of hepatic fibrosis, particularly after HCV treatment, the use of elastography, rather than biomarkers alone, is more appropriate.
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Affiliation(s)
| | - Júlia Oliveira Penteado
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
| | - Maiba Mikhael Nader
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Rossana Patrícia Basso
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | | | | | | | | | - Tchurle Hoffmann
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
| | - Leandro Farias Rodrigues
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Flavio Manoel Rodrigues da Silva Júnior
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
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Glyschewski L, Hahn A, Rohde H, Lütgehetmann M, Feldt T, Sarfo FS, Phillips RO, Dompreh A, Asibey SO, Boateng R, Weinreich F, Frickmann H, Eberhardt KA. Replicative co-infections with human immunodeficiency virus 1 and 2 as well as hepatitis B and C virus in Ghanaian individuals. Eur J Microbiol Immunol (Bp) 2024; 14:346-360. [PMID: 39475752 PMCID: PMC11836648 DOI: 10.1556/1886.2024.00103] [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: 09/21/2024] [Accepted: 10/14/2024] [Indexed: 12/19/2024] Open
Abstract
Background The study assessed replicative human immunodeficiency virus-(HIV-) infection and replicative co-infections as well as molecular determinants of reduced susceptibility towards anti-retroviral therapy in a Ghanaian population of known HIV patients and a control group. Methods Real-time PCRs for HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) were run with serum samples from known Ghanaian HIV-patients (n = 975) and control individuals (n = 105). For 108 individuals, HIV-sequence analysis was performed. Results Prevalence of replicative HIV-1 infection was 59.8% (583/975) in the known HIV-positive population and 2.9% (3/105) in the controls. Prevalences of replicative HBV-infection were comparable with 3.4% (33/975) in the HIV-positive individuals and 3.8% (4/105) in the controls. HIV-2 and HCV sequences were not recorded. Almost perfect concordance between two compared HIV-1-PCR assays was indicated by Fleiss' Kappa >0.8. Sanger sequencing indicated CRF_02AG, G and A3 as the quantitatively dominating HIV-1 subtypes, a minority of 3.4% CXCR4 tropism and high detection rates of mutations mediating reduced susceptibility towards nucleoside reverse transcriptase inhibitors (71.9%, 64/89), non-nucleoside reverse transcriptase inhibitors (95.5%, 85/89), protease inhibitors (95.9%, 93/97) and integrase inhibitors (22.4%, 22/98). Conclusions The assessment did not suggest HIV-triggered increased replication of HBV and HCV in the investigated Ghanaian population.
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Affiliation(s)
- Lynn Glyschewski
- Department of Microbiology and Hospital Hygiene, Bundeswehr Hospital Hamburg, Hamburg, Germany
| | - Andreas Hahn
- Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany
| | - Holger Rohde
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
| | - Torsten Feldt
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Medical Center Düsseldorf, Düsseldorf, Germany
| | - Fred Stephen Sarfo
- Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Albert Dompreh
- Department of Clinical Microbiology, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Richard Boateng
- Department of Clinical Microbiology, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Hagen Frickmann
- Department of Microbiology and Hospital Hygiene, Bundeswehr Hospital Hamburg, Hamburg, Germany
- Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany
| | - Kirsten Alexandra Eberhardt
- Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center, Hamburg, Germany
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Maekawa S, Takano S, Enomoto N. Risk of hepatocellular carcinoma after viral clearance achieved by DAA treatment. J Formos Med Assoc 2024; 123:1124-1130. [PMID: 38245398 DOI: 10.1016/j.jfma.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/22/2024] Open
Abstract
The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues.
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Affiliation(s)
- Shinya Maekawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
| | - Shinichi Takano
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuyuki Enomoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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Martín-Escolano R, Virseda-Berdices A, Berenguer J, González-García J, Brochado-Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, Resino S, Jiménez-Sousa MÁ. Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study. Front Pharmacol 2024; 15:1341612. [PMID: 39530457 PMCID: PMC11551606 DOI: 10.3389/fphar.2024.1341612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 10/04/2024] [Indexed: 11/16/2024] Open
Abstract
Background Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection. Methods We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. Results During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. Conclusion We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.
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Affiliation(s)
- Rubén Martín-Escolano
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Ana Virseda-Berdices
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Oscar Brochado-Kith
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Salvador Resino
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Ángeles Jiménez-Sousa
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Dinh DA, Tan Y, Saeed S. Disengagement from Care Among People Co-Infected with HIV and HCV: A Scoping Review. AIDS Behav 2024; 28:3381-3403. [PMID: 38992228 DOI: 10.1007/s10461-024-04436-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2024] [Indexed: 07/13/2024]
Abstract
Disengagement from care among people with HIV (PWH) and hepatitis C (HCV) increases the risks of adverse health outcomes and poses significant barriers to achieving global HIV and HCV elimination goals. In accordance with the Joanna Briggs Institute framework, a scoping review was conducted to synthesize and highlight existing gaps in the literature on (dis)engagement in care among PWH and HCV. We searched for original studies on (dis)engagement in care among PWH and HCV in high-income countries using eight electronic databases from inception to May 2023. Our search yielded 4462 non-duplicated records, which were scoped to 27 studies. Definitions of (dis)engagement in care were diverse, with considerable heterogeneity in how retention was operationalized and temporally measured. Studies identified predictors of (dis)engagement to be related to drug and substance use (n = 5 articles), clinical factors (n = 5), social and welfare (n = 4), and demographic characteristics (n = 2). When engagement in care was treated as an exposure, it was associated with HCV treatment initiation (n = 3), achieving sustained virological response (n = 2), and maintaining HIV viral suppression (n = 1). Interventions to improve care engagement among PWH and HCV were limited to five studies using cash incentives (n = 1) and individual case management (n = 4). (Dis)engagement in care is a dynamic process influenced by shifting priorities that may 'tip the balance' towards or away from regularly interacting with healthcare professionals. However, inconsistent definitions render cross-study comparisons and meta-analyses virtually impossible. Further research needs to establish a standardized definition to identify patients at high risk of disengagement and develop interventions that leverage the nested HIV/HCV care cascades to retain and recover patients lost from care.
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Affiliation(s)
- Duy A Dinh
- Faculty of Health Sciences, Queen's University, Kingston, ON, Canada
| | - Yvonne Tan
- Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Sahar Saeed
- Department of Public Health Sciences, Queen's University, 203 Carruthers Hall 62 Fifth Field Company Lane, Kingston, ON, K7L 3N6, Canada.
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Basoulis D, Mastrogianni E, Eliadi I, Papadopoulou M, Psichogiou M. HCV-HIV co-infection in people who inject drugs: Barriers to treatment and cure of HCV infection in the era of DAAs, a prospective study in Athens, Greece. HIV Med 2024; 25:1135-1144. [PMID: 39031579 DOI: 10.1111/hiv.13681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 05/29/2024] [Indexed: 07/22/2024]
Abstract
OBJECTIVES HIV/hepatitis C virus (HCV) co-infection among people who inject drugs (PWID) remains a global health problem. The goal of our study was to evaluate, in a real-world setting, success rates of sustained virological response (SVR) using direct-acting antivirals (DAAs) to treat a population of PWID living with HCV/HIV. METHODS This was a prospective single-center observational study. We collected demographic, socioeconomic, and clinical data pertaining to HIV and HCV infection in PWID with several barriers to care. We identified risk factors for SVR failure. RESULTS Among 130 individuals retained to HIV care, we planned HCV treatment in 119/130 (91.5%); 106/119 (89.1%) started treatment with DAAs and 100/106 (94.3%) completed treatment. People not starting treatment were more often in active opioid drug use (odds ratio [OR] 0.25; 95% confidence interval [CI] 0.07-0.97, p = 0.045) and benzodiazepine abuse (OR 0.25; 95% CI 0.07-0.95, p = 0.042). Only 86/100 (86%) were tested for SVR at 12 weeks (SVR12) and 72/86 (83.7%) achieved SVR. PWID in opioid substitution programmes tended to return for SVR12 testing more often (54.7% vs. 30%, p = 0.081). Individuals in active opioid drug use (OR 0.226; 95% CI 0.064-0.793, p = 0.02) or with poor adherence (OR 0.187; 95% CI 0.043-0.814, p = 0.025) were less likely to achieve SVR. At the end of our study period, 113/119 (95%) treatment-eligible patients remained alive. HCV infection was cured in 68/113 (61.1%) people. CONCLUSIONS Our findings underscore the importance of prioritizing combatting substance use to achieve HCV elimination goals. A systematic approach with effort to overcome barriers to receiving and completing treatment and encourage to enrol in opioid substitution programmes if not possible to completely abstain from use, can help increase chances of HCV cure.
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Affiliation(s)
- Dimitris Basoulis
- 1st Department of Internal Medicine, Laiko General Hospital, Athens, Greece
| | | | - Irene Eliadi
- 1st Department of Internal Medicine, Laiko General Hospital, Athens, Greece
| | | | - Mina Psichogiou
- 1st Department of Internal Medicine, Laiko General Hospital, Athens, Greece
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Santiago MJ, Chinnapaiyan S, Panda K, Rahman MS, Ghorai S, Rahman I, Black SM, Liu Y, Unwalla HJ. Altered Host microRNAomics in HIV Infections: Therapeutic Potentials and Limitations. Int J Mol Sci 2024; 25:8809. [PMID: 39201495 PMCID: PMC11354509 DOI: 10.3390/ijms25168809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/05/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
microRNAs have emerged as essential regulators of health and disease, attracting significant attention from researchers across diverse disciplines. Following their identification as noncoding oligonucleotides intricately involved in post-transcriptional regulation of protein expression, extensive efforts were devoted to elucidating and validating their roles in fundamental metabolic pathways and multiple pathologies. Viral infections are significant modifiers of the host microRNAome. Specifically, the Human Immunodeficiency Virus (HIV), which affects approximately 39 million people worldwide and has no definitive cure, was reported to induce significant changes in host cell miRNA profiles. Identifying and understanding the effects of the aberrant microRNAome holds potential for early detection and therapeutic designs. This review presents a comprehensive overview of the impact of HIV on host microRNAome. We aim to review the cause-and-effect relationship between the HIV-induced aberrant microRNAome that underscores miRNA's therapeutic potential and acknowledge its limitations.
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Affiliation(s)
- Maria J. Santiago
- Department of Chemistry and Biochemistry, Biochemistry Ph.D. Program, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (M.J.S.); (Y.L.)
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
| | - Srinivasan Chinnapaiyan
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
| | - Kingshuk Panda
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
| | - Md. Sohanur Rahman
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
| | - Suvankar Ghorai
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
| | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642, USA;
| | - Stephen M. Black
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
- Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA
| | - Yuan Liu
- Department of Chemistry and Biochemistry, Biochemistry Ph.D. Program, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (M.J.S.); (Y.L.)
- Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
| | - Hoshang J. Unwalla
- Department of Chemistry and Biochemistry, Biochemistry Ph.D. Program, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (M.J.S.); (Y.L.)
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA; (S.C.); (K.P.); (M.S.R.); (S.G.); (S.M.B.)
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Samaha H, Yigitkanli A, Naji A, Kazzi B, Tanios R, Dib SM, Ofotokun I, Rouphael N. Burden of Vaccine-Preventable Diseases in People Living with HIV. Vaccines (Basel) 2024; 12:780. [PMID: 39066418 PMCID: PMC11281599 DOI: 10.3390/vaccines12070780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/08/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH.
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Affiliation(s)
- Hady Samaha
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Arda Yigitkanli
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Amal Naji
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Bahaa Kazzi
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Ralph Tanios
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Serena Maria Dib
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
| | - Ighovwerha Ofotokun
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA 30322, USA;
| | - Nadine Rouphael
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA; (A.Y.); (A.N.); (B.K.); (R.T.); (S.M.D.); (N.R.)
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Stauffer WT, Goodman AZ, Gallay PA. Cyclophilin inhibition as a strategy for the treatment of human disease. Front Pharmacol 2024; 15:1417945. [PMID: 39045055 PMCID: PMC11264201 DOI: 10.3389/fphar.2024.1417945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/14/2024] [Indexed: 07/25/2024] Open
Abstract
Cyclophilins (Cyps), characterized as peptidyl-prolyl cis-trans isomerases (PPIases), are highly conserved and ubiquitous, playing a crucial role in protein folding and cellular signaling. This review summarizes the biochemical pathways mediated by Cyps, including their involvement in pathological states such as viral replication, inflammation, and cancer progression, to underscore the therapeutic potential of Cyp inhibition. The exploration of Cyp inhibitors (CypI) in this review, particularly non-immunosuppressive cyclosporine A (CsA) derivatives, highlights their significance as therapeutic agents. The structural and functional nuances of CsA derivatives are examined, including their efficacy, mechanism of action, and the balance between therapeutic benefits and off-target effects. The landscape of CypI is evaluated to emphasize the clinical need for targeted approaches to exploit the complex biology of Cyps and to propose future directions for research that may enhance the utility of non-immunosuppressive CsA derivatives in treating diseases where Cyps play a key pathological role.
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Affiliation(s)
| | | | - Philippe A. Gallay
- Department of Immunology & Microbiology, The Scripps Research Institute, La Jolla, CA, United States
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10
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Spera AM, Pagliano P, Conti V. Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now? World J Hepatol 2024; 16:661-666. [PMID: 38818300 PMCID: PMC11135269 DOI: 10.4254/wjh.v16.i5.661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/06/2024] [Accepted: 04/15/2024] [Indexed: 05/22/2024] Open
Abstract
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
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Affiliation(s)
- Anna Maria Spera
- Infectious Disease Unit, Universitary Hospital OORR San Giovanni di Dio e Ruggi d'Aragona, Salerno 84131, Italy.
| | - Pasquale Pagliano
- Department of Infectious Diseases, University of Salerno, Salerno 84131, Italy
| | - Valeria Conti
- Clinical Pharmacology and Pharmacogenetics Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno 84131, Italy
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11
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Osegueda A, Polo ML, Baquero L, Urioste A, Ghiglione Y, Paz S, Poblete G, Gonzalez Polo V, Turk G, Quiroga MF, Laufer N. Markers of Natural Killer Cell Exhaustion in HIV/HCV Coinfection and Their Dynamics After HCV Clearance Mediated by Direct-Acting Antivirals. Open Forum Infect Dis 2023; 10:ofad591. [PMID: 38107019 PMCID: PMC10723816 DOI: 10.1093/ofid/ofad591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 11/20/2023] [Indexed: 12/19/2023] Open
Abstract
Background Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs). Methods Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry. Results Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment. Conclusions Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.
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Affiliation(s)
- Ariel Osegueda
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina
| | - Maria Laura Polo
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina
| | - Lucia Baquero
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina
| | - Alejandra Urioste
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina
| | - Yanina Ghiglione
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina
| | - Silvia Paz
- Hospital Francisco Javier Muñiz, Buenos Aires, Argentina
| | | | - Virginia Gonzalez Polo
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina
| | - Gabriela Turk
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina
| | - Maria Florencia Quiroga
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina
| | - Natalia Laufer
- CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina
- Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina
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12
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Xinyu W, Qian W, Yanjun W, Jingwen K, Keying X, Jiazheng J, Haibing Z, Kai W, Xiao X, Lixing Z. Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases. Cell Death Dis 2023; 14:673. [PMID: 37828052 PMCID: PMC10570300 DOI: 10.1038/s41419-023-06170-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 08/07/2023] [Accepted: 09/21/2023] [Indexed: 10/14/2023]
Abstract
AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing to cell-cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS).Together, these data suggest that AF6 represents a novel regulator of RIPK1-RIPK3 dependent necroptotic pathway. Thus, the AF6-RIPK1-USP21 axis are potential therapeutic targets for treatment of various liver injuries and metabolic diseases.
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Affiliation(s)
- Wang Xinyu
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Wen Qian
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Wu Yanjun
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Kong Jingwen
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Xu Keying
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Jiao Jiazheng
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Zhang Haibing
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
| | - Wang Kai
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
| | - Xu Xiao
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
| | - Zhan Lixing
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
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13
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Liu J, Pan Y, Nelson MC, Gooden LK, Metsch LR, Rodriguez AE, Tross S, Del Rio C, Mandler RN, Feaster DJ. Strategies of Managing Repeated Measures: Using Synthetic Random Forest to Predict HIV Viral Suppression Status Among Hospitalized Persons with HIV. AIDS Behav 2023; 27:2915-2931. [PMID: 36739589 PMCID: PMC10403627 DOI: 10.1007/s10461-023-04015-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2023] [Indexed: 02/06/2023]
Abstract
The HIV/AIDS epidemic remains a major public health concern since the 1980s; untreated HIV infection has numerous consequences on quality of life. To optimize patients' health outcomes and to reduce HIV transmission, this study focused on vulnerable populations of people living with HIV (PLWH) and compared different predictive strategies for viral suppression using longitudinal or repeated measures. The four methods of predicting viral suppression are (1) including the repeated measures of each feature as predictors, (2) utilizing only the initial (baseline) value of the feature as predictor, (3) using the last observed value as the predictors and (4) using a growth curve estimated from the features to create individual-specific prediction of growth curves as features. This study suggested the individual-specific prediction of the growth curve performed the best in terms of lowest error rate on an independent set of test data.
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Affiliation(s)
- Jingxin Liu
- Department of Public Health, Miller School of Medicine, University of Miami, Coral Gables, USA.
- Soffer Clinical Research Ctr, 1120 NW 14th St, Room 1059, Miami, FL, 33136-2107, USA.
| | - Yue Pan
- Department of Public Health, Miller School of Medicine, University of Miami, Coral Gables, USA
| | - Mindy C Nelson
- Department of Public Health, Miller School of Medicine, University of Miami, Coral Gables, USA
| | - Lauren K Gooden
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, USA
| | - Lisa R Metsch
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, USA
| | | | - Susan Tross
- HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University Irving Medical Center, New York, NY, USA
| | - Carlos Del Rio
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Raul N Mandler
- Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
| | - Daniel J Feaster
- Department of Public Health, Miller School of Medicine, University of Miami, Coral Gables, USA
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14
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Yuwen L, Zhang S, Chao J. Recent Advances in DNA Nanotechnology-Enabled Biosensors for Virus Detection. BIOSENSORS 2023; 13:822. [PMID: 37622908 PMCID: PMC10452139 DOI: 10.3390/bios13080822] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/05/2023] [Accepted: 08/12/2023] [Indexed: 08/26/2023]
Abstract
Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.
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Affiliation(s)
- Lihui Yuwen
- State Key Laboratory of Organic Electronics and Information Displays, Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China; (L.Y.); (S.Z.)
| | - Shifeng Zhang
- State Key Laboratory of Organic Electronics and Information Displays, Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China; (L.Y.); (S.Z.)
| | - Jie Chao
- School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China
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15
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Dagostin F, Vanalli C, Boag B, Casagrandi R, Gatto M, Mari L, Cattadori IM. The enemy of my enemy is my friend: Immune-mediated facilitation contributes to fitness of co-infecting helminths. J Anim Ecol 2023; 92:477-491. [PMID: 36478135 DOI: 10.1111/1365-2656.13863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/28/2022] [Indexed: 12/12/2022]
Abstract
The conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated competition between parasites and yet there is ample evidence of positive interactions that could be generated by immune-mediated facilitation. We developed an immuno-epidemiological model and applied it to long-term data of two gastrointestinal helminths in two rabbit populations to investigate, through model testing, how immune-mediated mechanisms of parasite regulation could explain the higher intensities of both helminths in rabbits with dual than single infections. The model framework was selected and calibrated on rabbit population A and then validated on the nearby rabbit population B to confirm the consistency of the findings and the generality of the mechanisms. Simulations suggested that the higher intensities in rabbits with dual infections could be explained by a weakened or low species-specific IgA response and an asymmetric IgA cross-reaction. Simulations also indicated that rabbits with dual infections shed more free-living stages that survived for longer in the environment, implying greater transmission than stages from hosts with single infections. Temperature and humidity selectively affected the free-living stages of the two helminths. These patterns were comparable in the two rabbit populations and support the hypothesis that immune-mediated facilitation can contribute to greater parasite fitness and local persistence.
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Affiliation(s)
- Francesca Dagostin
- Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Italy.,Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Chiara Vanalli
- Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Brian Boag
- The James Hutton Institute, Invergowrie, UK
| | - Renato Casagrandi
- Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| | - Marino Gatto
- Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| | - Lorenzo Mari
- Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| | - Isabella M Cattadori
- Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, USA
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16
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Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis. J Clin Microbiol 2023; 61:e0133122. [PMID: 36537787 PMCID: PMC9879113 DOI: 10.1128/jcm.01331-22] [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: 12/24/2022] Open
Abstract
The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.
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17
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Long-Term Survivors in a Cohort of People Living with HIV Diagnosed between 1985 and 1994: Predictive Factors Associated with More Than 25 Years of Survival. Infect Dis Rep 2023; 15:70-83. [PMID: 36826348 PMCID: PMC9957088 DOI: 10.3390/idr15010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 01/11/2023] [Accepted: 01/17/2023] [Indexed: 01/24/2023] Open
Abstract
Although the mortality rate among individuals diagnosed during the pre-Highly Active Antiretroviral Treatment era has been substantial, a considerable number of them survived. Our study aimed to evaluate the prevalence of HIV long-term survivors in a cohort of People Living with HIV diagnosed between 1985 and 1994 and to speculate about potential predictive factors associated to long survival. This is a retrospective single-center study. Subjects surviving more than 300 months (25 years) from HIV diagnosis were defined as Long Term Survivors. Overall, 210 subjects were enrolled. More than 75.24% of the included people living with HIV were males, with a median age of 28 years (IQR 25-34). The prevalent risk factors for HIV infection were injection drug use (47.62%), followed by unprotected sex among heterosexual individuals (23.81%). Ninety-three individuals (44.29%) could be defined as LTS with a median (IQR) survival of 333 (312-377) months. A hazard ratio of 12.45 (95% CI 7.91-19.59) was found between individuals who were exposed to Highly Active AntiRetroviral Treatment (HAART) and individuals who were not, with the latter being at greater risk of death. The availability and accessibility of effective antiretroviral therapy for people living with HIV remain the cornerstone of survival.
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18
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Marshall AD, Martinello M, Treloar C, Matthews GV. Perceptions of hepatitis C treatment and reinfection risk among HIV-positive men who have sex with men and engage in high risk behaviours for hepatitis C transmission: The CEASE qualitative study. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2022; 109:103828. [PMID: 35994937 DOI: 10.1016/j.drugpo.2022.103828] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/07/2022] [Accepted: 08/08/2022] [Indexed: 10/31/2022]
Abstract
BACKGROUND Globally, treatment uptake for hepatitis C virus (HCV) infection among HIV-HCV coinfected men who have sex with men (MSM) has substantially increased since the advent of interferon-free direct-acting antivirals (DAA). However, HIV-positive MSM who engage in high risk behaviours are at an increased risk of HCV reinfection post-treatment. The aim of this study was to investigate perceptions of HCV diagnosis, treatment and reinfection risk among HCV-HIV coinfected MSM who engage in drug use and/or high risk sexual behavior in Sydney, Australia. METHODS Participants were recruited from the Control and Elimination within AuStralia of HEpatitis C from people living with HIV (CEASE) cohort (n=402) who reported engaging in drug use and/or high risk sexual behavior for transmission of HCV infection. Participants were interviewed about their perceptions of HCV diagnosis, treatment, and reinfection risk. Interview data were transcribed, coded, and analyzed thematically. RESULTS Of 33 participants interviewed (mean age 49 years), many participants were 'shocked' by their HCV diagnosis. Participants who believed they acquired HCV infection through sexual exposure felt it was important that their healthcare practitioner agreed with their perspective to mitigate stigmatizing experiences. Overall, participants expressed high satisfaction with their treatment experience due to long-standing therapeutic relationships with their HIV physician. Many participants expressed knowledge of how to prevent HCV reinfection from injection drug use, yet other than condom usage, most were unsure how to reduce high risk sexual activity with such discussions occurring less frequently with healthcare practitioners. CONCLUSION Findings indicate that MSM who engage in drug use and high risk sexual activity would benefit from additional education on reducing reinfection risk through sexual activity and services to reduce substance use, if requested.
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Affiliation(s)
- Alison D Marshall
- The Kirby Institute, UNSW Sydney, Sydney, Australia; Centre for Social Research in Health, UNSW Sydney, Sydney, Australia.
| | | | - Carla Treloar
- Centre for Social Research in Health, UNSW Sydney, Sydney, Australia
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19
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Hepatitis C virus (HCV) seroprevalence, RNA detection, and genotype distribution across Florida, 2015-2018. Prev Med 2022; 161:107136. [PMID: 35803347 PMCID: PMC9598903 DOI: 10.1016/j.ypmed.2022.107136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/14/2022] [Accepted: 07/02/2022] [Indexed: 11/21/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC) in the U.S. Due to high rates of HCV among baby boomers (born 1945-1965), it was recommended they receive universal screening. This was expanded to all U.S. adults in 2020 due to evidence of increasing rates of chronic HCV in younger adults. An assessment of HCV burden across demographics is crucial to understand the future burden of HCC and target under-screened adults for HCV. Using the OneFlorida Clinical Research Consortium, of more than one million individuals in Florida, all HCV antibody and viral RNA tests completed from 2015 to 2018 were identified. HCV seroprevalence, HCV viral load (active infection), and HCV genotype distribution by risk groups were assessed. Overall, HCV seroprevalence and active infection were highest among White non-Hispanic individuals, males, and baby boomers. However, odds of a positive HCV antibody test were higher among Black non-Hispanic individuals born before 1945 (aOR: 2.74; 95% CI: 1.98-3.78) or 1945-1965 (aOR: 1.46; 95% CI: 1.36-1.56) compared to White non-Hispanic individuals. In contrast, among individuals born after 1965, Black non-Hispanics were less likely than White non-Hispanics to test HCV antibody positive (aOR of 0.5-0.28). A similar age/race pattern was observed for active HCV infection. There was a higher prevalence of genotype 1A and 3 and lower prevalence of 1B in younger adults. Patterns of HCV seroprevalence and active HCV infection identified in our study support the recent shift from age and risk-based screening guidelines to universal adult screening.
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20
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Altinbas A, Holmes JA, Salloum S, Lidofsky A, Alatrakchi N, Somsouk M, Hunt P, Deeks S, Chew KW, Lauer G, Kruger A, Lin W, Chung RT. LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients. Biomark Med 2022; 16:839-846. [PMID: 35786977 PMCID: PMC9437769 DOI: 10.2217/bmm-2021-0596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 05/27/2022] [Indexed: 01/11/2023] Open
Abstract
Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.
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Affiliation(s)
- Akif Altinbas
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Jacinta A Holmes
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Shadi Salloum
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Anna Lidofsky
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Nadia Alatrakchi
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Ma Somsouk
- Department of Medicine, University of California San Francisco, School of Medicine, San Francisco, CA 94143, USA
| | - Peter Hunt
- Department of Medicine, University of California San Francisco, School of Medicine, San Francisco, CA 94143, USA
| | - Steven Deeks
- Department of Medicine, University of California San Francisco, School of Medicine, San Francisco, CA 94143, USA
| | - Kara W Chew
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Georg Lauer
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Annie Kruger
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Wenyu Lin
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
| | - Raymond T Chung
- Department of Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA 02114, USA
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21
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Impact of HIV-1 Infection on the Natural Progress of an Anti-HCV Positive Population in an Impoverished Village in China from 2009 to 2017. Viruses 2022; 14:v14081621. [PMID: 35893687 PMCID: PMC9330172 DOI: 10.3390/v14081621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 12/02/2022] Open
Abstract
Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.
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22
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Yang X, Jeong K, Yabes JG, Ragni MV. Prevalence and risk factors for hepatocellular carcinoma in individuals with haemophilia in the era of direct-acting antiviral agents: A national inpatient sample study. Haemophilia 2022; 28:769-775. [PMID: 35727998 DOI: 10.1111/hae.14607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/08/2022] [Accepted: 06/01/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection. Among haemophilic (H) men, HCV is the leading cause of liver disease. Direct-acting antiviral agents (DAA) reduce HCV viral load, but impact on HCC is unknown. METHODS This was a retrospective study of adult H and nonhaemophilic (NH) male discharges, with and without HCC, identified by ICD-10 codes in the National Inpatient Sample (NIS) database, 2016-2018, with DAA availability. Analyses included discharge-level weights to reflect national estimates. Categorical variables were assessed by Rao-Scott chi-square and continuous variables by weighted simple linear regression. HCC correlates were determined by weighted multivariable logistic regression. RESULTS Among 7,674,969 adult male discharges, 3730 H (.04%) were identified in 2016-2018, of whom 10.06% had HCV and 1.07% had HCC, significantly higher than NH (1.22% and .27%, respectively) all P < .001. Annual HCC rates were similar during the 3-year period (2016-2018) in H and NH. Among H, HCC is associated with older age and higher rates of HCV, HBV, NASH, end-stage liver disease, and Charlson comorbidity (CCI), each P < .001. Among HCC, H were younger and more likely HIV+, each P < .001, but less likely alcoholic (P = .018) or hyperlipidaemic (P = .008) compared to NH. In multivariable regression, risk factors for HCC among H included NASH (OR 21.6), HCV (OR 3.96), CCI (OR1.54), all P < .001, while HIV and hyperlipidaemia were protective. CONCLUSION From 2016 to 2018, HCC rates did not change significantly in haemophilia discharges. NASH, HCV, and CCI are significant risks for HCC in haemophilia during the DAA-era.
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Affiliation(s)
- Xi Yang
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
| | - Kwonho Jeong
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jonathan G Yabes
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Margaret V Ragni
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
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23
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Sepúlveda-Crespo D, Yélamos MB, Díez C, Gómez J, Hontañón V, Torresano-Felipe F, Berenguer J, González-García J, Ibañez-Samaniego L, Llop E, Olveira A, Martínez J, Resino S, Martínez I. Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis. Biomed Pharmacother 2022; 150:113024. [PMID: 35483197 DOI: 10.1016/j.biopha.2022.113024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/20/2022] [Accepted: 04/20/2022] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES The current study aimed to assess the impact of HIV on the production of anti-HCV antibodies in HCV-infected individuals with advanced HCV-related cirrhosis before and 36 weeks after the sustained virological response (SVR) induced by direct-acting antivirals (DAAs) therapy. METHODS Prospective study on 62 patients (50 HIV/HCV-coinfected and 12 HCV-monoinfected). Plasma anti-E2 and HCV-nAbs were determined respectively by ELISA and microneutralization assays. RESULTS At baseline, the HCV-group had higher anti-E2 levels against Gt1a (p = 0.012), Gt1b (p = 0.023), and Gt4a (p = 0.005) than the HIV/HCV-group. After SVR, anti-E2 titers against Gt1a (p < 0.001), Gt1b (p = 0.001), and Gt4a (p = 0.042) were also higher in the HCV-group than HIV/HCV-group. At 36 weeks post-SVR, plasma anti-E2 titers decreased between 1.3 and 1.9-fold in the HIV/HCV-group (p < 0.001) and between 1.5 and 1.8-fold in the HCV-group (p ≤ 0.001). At baseline, the HCV-group had higher titers of HCV-nAbs against Gt1a (p = 0.022), Gt1b (p = 0.002), Gt2a (p < 0.001), and Gt4a (p < 0.001) than the HIV/HCV-group. After SVR, HCV-nAbs titers against Gt1a (p = 0.014), Gt1b (p < 0.001), Gt2a (p = 0.002), and Gt4a (p = 0.004) were also higher in the HCV-group. At 36 weeks post-SVR, HCV-nAbs decreased between 2.6 and 4.1-fold in the HIV/HCV-group (p < 0.001) and between 1.9 and 4.0-fold in the HCV-group (p ≤ 0.001). CONCLUSIONS HIV/HCV-coinfected patients produced lower levels of broad-spectrum anti-HCV antibodies than HCV-monoinfected patients.
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Affiliation(s)
- Daniel Sepúlveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - María Belén Yélamos
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Julián Gómez
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain
| | - Víctor Hontañón
- Unidad de VIH; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain
| | - Francisco Torresano-Felipe
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de VIH; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain
| | - Luis Ibañez-Samaniego
- Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Elva Llop
- Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Antonio Olveira
- Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain; Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
| | - Javier Martínez
- Servicio de Aparato Digestivo, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
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24
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Shikuma CM, Le T, Phuong TV, Chew GM, Nguyen VVC, Vo TL, Siriwardhana C, Chow D, Ghukasyan H, Limpruttidham N, Premeaux T, Gangcuangco LM, Paul R, Ndhlovu LC. Immunologic Change over 72 Weeks Following Raltegravir- Versus Efavirenz-Based Therapy in HIV/HCV-Coinfected Individuals in Vietnam. AIDS Res Hum Retroviruses 2022; 38:441-450. [PMID: 34861767 PMCID: PMC10027344 DOI: 10.1089/aid.2021.0076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38+HLA-DR+, PD1+, and TIGIT+ CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p < .01). Most parameters did not normalize despite 72 weeks of ART. In particular sCD163 persisted at high levels. Improvement over 72 weeks in fibrosis as assessed by FibroScan® correlated with reductions in plasma sCD163 and in the frequencies of T cell activation, single PD1+, TIGIT+, and dual PD1+TIGIT+ CD8 T cells. A nonsignificant tendency toward more favorable effects on monocyte and T cell immune activation and on T cell exhaustion were seen with RAL-compared with EFV-based therapy. The initiation of ART in HIV/HCV-coinfected individuals is associated with incomplete improvement in monocyte and T cell immune activation and exhaustion, which was associated with some corresponding improvement in liver fibrosis.
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Affiliation(s)
- Cecilia M. Shikuma
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Thuy Le
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
- Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | - Thao Vu Phuong
- Department of Medicine, University of Saskatchewan, Saskatoon, Canada
- Saskatchewan Infectious Disease Care Network, Saskatoon, Canada
| | - Glen M. Chew
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | | | - Trieu Ly Vo
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
- Department of Infectious Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Chathura Siriwardhana
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Dominic Chow
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Hayk Ghukasyan
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Nath Limpruttidham
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Thomas Premeaux
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Louie Mar Gangcuangco
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Robert Paul
- Department of Psychological Sciences, Missouri Institute of Mental Health, University of Missouri–St. Louis, St. Louis, Missouri, USA
| | - Lishomwa C. Ndhlovu
- Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
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25
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Qian T, Fujiwara N, Koneru B, Ono A, Kubota N, Jajoriya AK, Tung MG, Crouchet E, Song WM, Marquez CA, Panda G, Hoshida A, Raman I, Li QZ, Lewis C, Yopp A, Rich NE, Singal AG, Nakagawa S, Goossens N, Higashi T, Koh AP, Bian CB, Hoshida H, Tabrizian P, Gunasekaran G, Florman S, Schwarz ME, Hiotis SP, Nakahara T, Aikata H, Murakami E, Beppu T, Baba H, Warren A, Bhatia S, Kobayashi M, Kumada H, Fobar AJ, Parikh ND, Marrero JA, Rwema SH, Nair V, Patel M, Kim-Schulze S, Corey K, O’Leary JG, Klintmalm GB, Thomas DL, Dibas M, Rodriguez G, Zhang B, Friedman SL, Baumert TF, Fuchs BC, Chayama K, Zhu S, Chung RT, Hoshida Y. Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development. Gastroenterology 2022; 162:1210-1225. [PMID: 34951993 PMCID: PMC8934284 DOI: 10.1053/j.gastro.2021.12.250] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND & AIMS There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. METHODS A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). RESULTS A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. CONCLUSION The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.
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Affiliation(s)
- Tongqi Qian
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Naoto Fujiwara
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Bhuvaneswari Koneru
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Atsushi Ono
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoto Kubota
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Arun K Jajoriya
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Matthew G Tung
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, U.S
| | - Emilie Crouchet
- Institut de Recherche sur les Maladies Virales et Hépatiques, Inserm U1110, University of Strasbourg, Strasbourg, France
| | - Won-Min Song
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Cesia Ammi Marquez
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Gayatri Panda
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Ayaka Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Indu Raman
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Quan-Zhen Li
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Cheryl Lewis
- Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Adam Yopp
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Nicole E Rich
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Switzerland
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Anna P Koh
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - C Billie Bian
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Hiroki Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Ganesh Gunasekaran
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Myron E Schwarz
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Spiros P Hiotis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toru Beppu
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Hideo Baba
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | | | | | | | | | - Austin J Fobar
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, U.S
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, U.S
| | - Jorge A Marrero
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, U.S
| | | | - Venugopalan Nair
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Manishkumar Patel
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | | | - Kathleen Corey
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, U.S
| | | | | | - David L Thomas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, U.S
| | | | | | - Bin Zhang
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Scott L Friedman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Thomas F Baumert
- Institut de Recherche sur les Maladies Virales et Hépatiques, Inserm U1110, University of Strasbourg, Strasbourg, France.,IHU, Pole hépato-digestif, Strasbourg University Hospitals, Strasbourg, France
| | - Bryan C Fuchs
- Department of Surgery, Massachusetts General Hospital, Boston, U.S., Ferring Pharmaceuticals, San Diego, U.S
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Shijia Zhu
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Raymond T Chung
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Yujin Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
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26
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Yang R, Gui X, Ke H, Xiong Y, Gao S. Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection. AIDS Res Ther 2021; 18:98. [PMID: 34924016 PMCID: PMC8684625 DOI: 10.1186/s12981-021-00419-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/23/2021] [Indexed: 11/12/2022] Open
Abstract
Background Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. Methods This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. Results Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009–0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2–5 years and 5–10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). Conclusion cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection. Supplementary Information The online version contains supplementary material available at 10.1186/s12981-021-00419-y.
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Shrivastava S, Kottilil S, Sherman KE, Masur H, Tang L. CCR5+ T-Cells Homed to the Liver Exhibit Inflammatory and Profibrogenic Signatures in Chronic HIV/HCV-Coinfected Patients. Viruses 2021; 13:v13102074. [PMID: 34696504 PMCID: PMC8539814 DOI: 10.3390/v13102074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/08/2021] [Accepted: 10/10/2021] [Indexed: 11/16/2022] Open
Abstract
Liver fibrosis is accelerated in patients coinfected with hepatitis C virus and human immunodeficiency virus (HIV), compared with HCV monoinfected patients, although the underlying mechanisms are unknown. We hypothesize that T cells expressing the HIV co-receptor, chemokine receptor 5 (CCR5), preferentially migrate to the inflamed liver and contribute to enhanced fibrogenesis. We compared the peripheral and intrahepatic CCR5 expression on CD4+ and CD8+ T cells in 21 HIV/HCV-coinfected patients with 14 chronic HCV monoinfected patients. Using 12-color flow cytometry, phenotypic and functional characterization of CCR5+ and negative cells pre- and post-stimulation with HCV genotype specific overlapping pooled peptides was conducted. Patients with HIV/HCV coinfection had significantly more CD4+CCR5+ and CD8+CCR5+ T cells in the liver as compared with peripheral blood (p = 0.0001 for both). Compared with patients with HCV monoinfection, patients with HIV/HCV coinfection also had fewer peripheral CD4+CCR5+ and CD8+CCR5+ T cells (p = 0.02, p = 0.001 respectively), but more intrahepatic CD4+CCR5+ and CD8+CCR5+ cells (p = 0.0001 for both). Phenotypic analysis of CCR5+ sorted cells demonstrated an increased expression of markers of exhaustion, senescence, immune activation and liver homing (PD1, CD57, CD38, HLADR, and CXCR3). Post-stimulation with HCV peptides, CCR5+ T cells secreted more proinflammatory and profibrogenic cytokines and chemokines rather than antiviral cytokines. Phenotypic and functional analyses of CCR5+ T cells in HIV/HCV-coinfected patients revealed a pathogenic role for CCR5+ T cells in hepatic fibrogenesis. These cells are functionally proinflammatory, pro-fibrogenic and preferentially accumulate in liver, accelerating fibrosis. These findings suggest that targeting CCR5 may be a therapeutic strategy for be ameliorating liver fibrosis.
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Affiliation(s)
- Shikha Shrivastava
- Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA;
| | - Shyam Kottilil
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA
| | - Kenneth E. Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinatti, OH 45267, USA;
| | - Henry Masur
- National Institutes of Health, Bethesda, MD 20892, USA;
| | - Lydia Tang
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD 21201, USA
- Correspondence:
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Kobayashi T, Yasuno T, Takahashi K, Nakamura S, Mashino T, Ohe T. Novel pyridinium-type fullerene derivatives as multitargeting inhibitors of HIV-1 reverse transcriptase, HIV-1 protease, and HCV NS5B polymerase. Bioorg Med Chem Lett 2021; 49:128267. [PMID: 34271071 DOI: 10.1016/j.bmcl.2021.128267] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/05/2021] [Accepted: 07/11/2021] [Indexed: 11/26/2022]
Abstract
In the present study, we newly synthesized four types of novel fullerene derivatives: pyridinium/ethyl ester-type derivatives 3b-3l, pyridinium/carboxylic acid-type derivatives 4a, 4e, 4f, pyridinium/amide-type derivative 5a, and pyridinium/2-morpholinone-type derivative 6a. Among the assessed compounds, cis-3c, cis-3d, trans-3e, trans-3h, cis-3l, cis-4e, cis-4f, trans-4f, and cis-5a were found to inhibit HIV-1 reverse transcriptase (HIV-RT), HIV-1 protease (HIV-PR), and HCV NS5B polymerase (HCV NS5B), with IC50 values observed in the micromolar range. Cellular uptake of pyridinium/ethyl ester-type derivatives was higher than that of corresponding pyridinium/carboxylic acid-type derivatives and pyridinium/amide-type derivatives. This result might indicate that pyridinium/ethyl ester-type derivatives are expected to be lead compounds for multitargeting drugs to treat HIV/HCV coinfection.
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Affiliation(s)
- Toi Kobayashi
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan
| | - Takumi Yasuno
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan
| | - Kyoko Takahashi
- Department of Chemistry, Nippon Medical School, 1-7-1 Kyonan-cho, Musashino, Tokyo, Japan
| | - Shigeo Nakamura
- Department of Chemistry, Nippon Medical School, 1-7-1 Kyonan-cho, Musashino, Tokyo, Japan
| | - Tadahiko Mashino
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan
| | - Tomoyuki Ohe
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan.
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Kumar N, Prabhu SS, Monga I, Banerjee I. Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis. Meta Gene 2021. [DOI: 10.1016/j.mgene.2021.100909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Gobran ST, Ancuta P, Shoukry NH. A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection. Front Immunol 2021; 12:726419. [PMID: 34456931 PMCID: PMC8387722 DOI: 10.3389/fimmu.2021.726419] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 07/26/2021] [Indexed: 12/13/2022] Open
Abstract
Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.
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Affiliation(s)
- Samaa T Gobran
- Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.,Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada.,Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Petronela Ancuta
- Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.,Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Naglaa H Shoukry
- Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.,Département de médecine, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
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Herderschee J, Heinonen T, Fenwick C, Schrijver IT, Ohmiti K, Moradpour D, Cavassini M, Pantaleo G, Roger T, Calandra T. High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus. Clin Microbiol Infect 2021; 28:611.e1-611.e7. [PMID: 34474121 DOI: 10.1016/j.cmi.2021.08.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 08/18/2021] [Accepted: 08/21/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVES Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. METHODS Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. RESULTS HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56dim natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. CONCLUSIONS Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.
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Affiliation(s)
- Jacobus Herderschee
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Tytti Heinonen
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Craig Fenwick
- Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Irene T Schrijver
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Khalid Ohmiti
- Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Matthias Cavassini
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Giuseppe Pantaleo
- Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Swiss Vaccine Research Institute, Lausanne, Switzerland
| | - Thierry Roger
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Thierry Calandra
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Mukhatayeva A, Mustafa A, Dzissyuk N, Issanov A, Bayserkin B, Vermund SH, Ali S. Hepatitis B, Hepatitis C, tuberculosis and sexually-transmitted infections among HIV positive patients in Kazakhstan. Sci Rep 2021; 11:13542. [PMID: 34188081 PMCID: PMC8241865 DOI: 10.1038/s41598-021-92688-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 06/07/2021] [Indexed: 11/29/2022] Open
Abstract
In contrast with global trends, HIV prevalence in Kazakhstan and other Central Asian countries has been rising in recent years. In this study, we analyzed hepatitis B (HBV), hepatitis C (HCV), tuberculosis (TB) and sexually-transmitted (STI) co-infections among 500 HIV positive study participants recruited from all regions of Kazakhstan. Among our study participants, 27%, 8%, 2%, and 5% were coinfected with, respectively, HCV, TB, HBV, and STI. A considerable proportion of the study participants was also found with triple or quadruple infections of HCV/TB (12%), TB/STI (0.8%), HCV/STI (2%), HCV/HBV (1%), HBV/TB (0.4%), HBV/STI (0.2%), HBV/HCV/TB (0.4%), HBV/HCV/STI (0.2%), or HCV/TB/STI (0.2%). Strong associations were found of certain age groups, duration of HIV infection, and practices of injection drug use and sexual contact with PLWH, with co-infections of HIV/HCV and HIV/TB. The odds of having death was 4.07 times higher with TB/HIV as compared to other co-infections. Co-occurrence of HIV with HCV, HBV, and TB infections among participants of this study highlights the necessity of regular screening for HCV infection among HIV infected patients, together with implementation of vigilant vaccination protocols against HBV and TB. Additionally, persons who inject drugs especially need to be focused for harm reduction efforts that include opiate substitution therapy, needle or syringe exchange programs, regular screening, and increased availability of ART and direct acting antivirals.
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Affiliation(s)
- Ainur Mukhatayeva
- Department of Biomedical Sciences, Nazarbayev School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Aidana Mustafa
- Department of Biomedical Sciences, Nazarbayev School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Natalya Dzissyuk
- Kazakh Scientific Center of Dermatology and Infectious Diseases, Almaty, Kazakhstan
| | - Alpamys Issanov
- Department of Biomedical Sciences, Nazarbayev School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Bauyrzhan Bayserkin
- Kazakh Scientific Center of Dermatology and Infectious Diseases, Almaty, Kazakhstan
| | | | - Syed Ali
- Department of Biomedical Sciences, Nazarbayev School of Medicine, Nazarbayev University, Astana, Kazakhstan.
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Melaram R. Environmental Risk Factors Implicated in Liver Disease: A Mini-Review. Front Public Health 2021; 9:683719. [PMID: 34249849 PMCID: PMC8264448 DOI: 10.3389/fpubh.2021.683719] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/17/2021] [Indexed: 01/08/2023] Open
Abstract
Liver disease is a global health issue, resulting in about two million deaths per year. It encompasses a wide spectrum of varied or unknown etiologies, ranging from lifestyle choices to pre-existing comorbidities. In recent decades, exposure to environmental toxins and subsequent liver health outcomes have captured public interest, due to the extensive application of pesticides, consumption of aflatoxin contaminated foodstuff, and cyanobacterial harmful algae blooms in endemic regions of liver disease. Hepatocellular carcinoma is a serious and debilitating condition of the liver, characterized by abdominal pain and unexplained weight loss. Established risk factors for hepatocellular carcinoma include alcohol consumption, cigarette smoking, and viral infections of hepatitis B and C. However, mounting evidence suggests that environmental toxins may represent an important contributing factor in hepatocellular carcinoma development. This mini-review synthesizes epidemiological investigations, providing evidence for environmental toxins as one potential risk factor for liver disease.
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Affiliation(s)
- Rajesh Melaram
- School of Health Sciences, Walden University, Minneapolis, MN, United States
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Immunovirological Assessment of HIV-Infected Patients and Phylogenetic Analysis of the Virus in Northeast of Iran. Jundishapur J Microbiol 2021. [DOI: 10.5812/jjm.112123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: The reliable laboratory tests, co-infection with other tumor viruses, and determining the genetic types are very important for therapy and monitoring of the clinical status of human immunodeficiency virus (HIV)-infected subjects. Objectives: This study evaluated the co-infection of HIV with hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell leukemia virus type 1 (HTLV-1), the viral load, the progression of infection, and its correlation with the clinical status. Methods: Twenty HIV-infected cases were assessed for T cell subpopulations, HBV, HCV, and HTLV-1 co-infection, as well as the viral load. For phylogenetic relationships analysis, the HIV-c2-v5 fragment and p17 of gag were amplified, sequenced, and then clustered using phylogenetic analysis by MEGA software with maximum-likelihood. Results: The quantity of HIV viral load by qRT-PCR (TaqMan) and Cobas-Amplicor monitor test had a very strong correlation (R = 0.881, P < 0.0001). A significant negative correlation was also found between CD4+ cell count and Cobas-Amplicor (R = -0.41, P = 0.06). A significant negative correlation was also found between CD4+ cell count and Cobas-Amplicor (R = -0.41, P = 0.06) with HIV monitor test results (R = -0.41, P = 0.06). The phylogenetic analysis for p17 regions in gag and c2-v5 in env genes showed that all subjects had AD genotype. The co-infection of the HIV subjects with HBV, HCV, and HTLV-1 was 75%, 75%, and 15%, respectively. A direct correlation was observed between CD8+ and HIV-HTLV-1 co-infection. Conclusions: The results showed that HIV CRF35-AD, (M group) is more frequent in the northeast of Iran, and both real-time quantification methods were reliable for monitoring the HIV-1 viral load. In addition, the transmission rate of HTLV-1 is lower than HBV and HCV among drug abusers.
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Quaranta MG, Ferrigno L, Tata X, D'Angelo F, Coppola C, Ciancio A, Bruno SR, Loi M, Giorgini A, Margotti M, Cossiga V, Brancaccio G, Dallio M, De Siena M, Cannizzaro M, Cavalletto L, Massari M, Mazzitelli M, De Leo P, Laccabue D, Baiocchi L, Kondili LA. Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort. BMC Infect Dis 2021; 21:413. [PMID: 33947337 PMCID: PMC8094561 DOI: 10.1186/s12879-021-06053-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 04/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. METHODS Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. RESULTS We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0-44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00-6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18-3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08-2.85) and increased INR (HR = 2.41; 95% CI 1.51-3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83). CONCLUSIONS Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.
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Affiliation(s)
- Maria Giovanna Quaranta
- Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Luigina Ferrigno
- Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Xhimi Tata
- University of Tor Vergata, Nostra Signora del Buon Consiglio di Tirana, Tirana, Albania
| | - Franca D'Angelo
- Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | | | | | | | - Martina Loi
- Liver Unit, University Hospital, Monserrato, Cagliari, Italy
| | - Alessia Giorgini
- Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Marzia Margotti
- Department of Internal Medicine, University Hospital of Modena, Modena, Italy
| | - Valentina Cossiga
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | | | - Marcello Dallio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Martina De Siena
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marco Cannizzaro
- Internal Medicine, Villa Sofia-Cervello Hospital, Palermo, Italy
| | - Luisa Cavalletto
- Department of Medicine, University Hospital of Padua, Padua, Italy
| | - Marco Massari
- Infectious Diseases, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Maria Mazzitelli
- Department of Infectious Disease, University Hospital Mater Domini, Catanzaro, Italy
| | | | - Diletta Laccabue
- Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Leonardo Baiocchi
- Department of Medical Sciences, University of Tor Vergata, Rome, Italy
| | - Loreta A Kondili
- Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
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Gunasinghe SD, Peres NG, Goyette J, Gaus K. Biomechanics of T Cell Dysfunctions in Chronic Diseases. Front Immunol 2021; 12:600829. [PMID: 33717081 PMCID: PMC7948521 DOI: 10.3389/fimmu.2021.600829] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 01/12/2021] [Indexed: 12/12/2022] Open
Abstract
Understanding the mechanisms behind T cell dysfunctions during chronic diseases is critical in developing effective immunotherapies. As demonstrated by several animal models and human studies, T cell dysfunctions are induced during chronic diseases, spanning from infections to cancer. Although factors governing the onset and the extent of the functional impairment of T cells can differ during infections and cancer, most dysfunctional phenotypes share common phenotypic traits in their immune receptor and biophysical landscape. Through the latest developments in biophysical techniques applied to explore cell membrane and receptor-ligand dynamics, we are able to dissect and gain further insights into the driving mechanisms behind T cell dysfunctions. These insights may prove useful in developing immunotherapies aimed at reinvigorating our immune system to fight off infections and malignancies more effectively. The recent success with checkpoint inhibitors in treating cancer opens new avenues to develop more effective, targeted immunotherapies. Here, we highlight the studies focused on the transformation of the biophysical landscape during infections and cancer, and how T cell biomechanics shaped the immunopathology associated with chronic diseases.
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Affiliation(s)
- Sachith D Gunasinghe
- EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, NSW, Australia.,ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW, Australia
| | - Newton G Peres
- EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, NSW, Australia.,ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW, Australia
| | - Jesse Goyette
- EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, NSW, Australia.,ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW, Australia
| | - Katharina Gaus
- EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, NSW, Australia.,ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW, Australia
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Ramesh D, Vijayakumar BG, Kannan T. Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections. ChemMedChem 2021; 16:1403-1419. [PMID: 33427377 DOI: 10.1002/cmdc.202000849] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Indexed: 12/13/2022]
Abstract
Nucleoside and nucleotide analogues are structurally similar antimetabolites and are promising small-molecule chemotherapeutic agents against various infectious DNA and RNA viruses. To date, these analogues have not been documented in-depth as anti-human immunodeficiency virus (HIV) and anti-hepatitis virus agents, these are at various stages of testing ranging from pre-clinical, to those withdrawn from trials, or those that are approved as drugs. Hence, in this review, the importance of these analogues in tackling HIV and hepatitis virus infections is discussed with a focus on the viral genome and the mechanism of action of these analogues, both in a mutually exclusive manner and their role in HIV/hepatitis coinfection. This review encompasses nucleoside and nucleotide analogues from 1987 onwards, starting with the first nucleoside analogue, zidovudine, and going on to those in current clinical trials and even the drugs that have been withdrawn. This review also sheds light on the prospects of these nucleoside analogues in clinical trials as a treatment option for the COVID-19 pandemic.
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Affiliation(s)
- Deepthi Ramesh
- Department of Chemistry, Pondicherry University, Kalapet, Puducherry, 605014, India
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38
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Medrano LM, Berenguer J, Salgüero S, González-García J, Díez C, Hontañón V, Garcia-Broncano P, Ibañez-Samaniego L, Bellón JM, Jiménez-Sousa MA, Resino S. Successful HCV Therapy Reduces Liver Disease Severity and Inflammation Biomarkers in HIV/HCV-Coinfected Patients With Advanced Cirrhosis: A Cohort Study. Front Med (Lausanne) 2021; 8:615342. [PMID: 33598470 PMCID: PMC7882604 DOI: 10.3389/fmed.2021.615342] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/04/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis. Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay. Results: We found significant decreases in severity scores of liver disease [LSM (q-value < 0.001), HVPG (q-value = 0.011), and CTP (q-value = 0.045)] and plasma biomarkers [LBP (q-value < 0.001), IP-10 (q-value < 0.001), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), IL-1RA (q-value = 0.013), OPG (q-value < 0.001), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), PAI-1 (q-value = 0.001), and VEGF-A (q-value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP (q-value < 0.001), IP-10 (q-value < 0.001), MCP-1 (q-value = 0.008), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), OPG (q-value = 0.004), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), and PAI-1 (q-value = 0.002). For CTP values, we found significant positive associations with IP-10 (q-value = 0.010), IL-6 (q-value = 0.010), IL-1RA (q-value = 0.033), and sICAM-1 (q-value = 0.010). Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.
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Affiliation(s)
- Luz Maria Medrano
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Sergio Salgüero
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.,Unidad de Análisis Clínicos, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Juan González-García
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz"/IdiPAZ, Madrid, Spain
| | - Cristina Díez
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Víctor Hontañón
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz"/IdiPAZ, Madrid, Spain
| | - Pilar Garcia-Broncano
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.,Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
| | - Luis Ibañez-Samaniego
- Servicio de Aparato Digestivo, Hospital General Universitario "Gregorio Marañón", Madrid, Spain
| | - José M Bellón
- Fundación para la Investigación Biomédica, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María Angeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
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Moghoofei M, Najafipour S, Mostafaei S, Tavakoli A, Bokharaei-Salim F, Ghorbani S, Javanmard D, Ghaffari H, Monavari SH. MicroRNAs Profiling in HIV, HCV, and HIV/HCV Co-Infected Patients. Curr HIV Res 2021; 19:27-34. [PMID: 32900348 DOI: 10.2174/1570162x18666200908112113] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 08/11/2020] [Accepted: 08/18/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are important public health issues. OBJECTIVE This study aimed to assess the association between microRNAs expression leveland immunological and viral markers in HIV, HCV, and HIV/HCV co-infected patients. METHODS The expression level of miR-29, miR-149, miR-199, miR-let7, miR-223, miR-155, miR-122, and miR-150 was evaluated in 20 HIV, 20 HCV, 20 co-infected patients, and 20 healthy controls using real-time PCR assay. HIV and HCVviral loads were measuredby real-time PCR, and also, CD4+ T-lymphocyte count was measuredby the PIMA CD4 analyzer. RESULTS The miRNA expression pattern in each mentioned group showed significantly different expression profiles, but some miRNA species were shared between the groups. MiR-122 and miR-155 were upregulated, while miR-29 and miR-223 were downregulated in three patients groups compared to healthy controls. A significant positive correlation was observed between the expression of miR-122 and HIV/HCV loads. But, miR-29 and let-7 were negatively correlated with HIV load, and miR-149 and let-7 were negatively correlated with HCV load. Also, miR-155 was positively correlated with HCV load. MiR-122 and miR-199 were negative while others were positively correlated with CD4+ T cell count. CONCLUSION These miRNAs are probably involved in the clinical progression and pathogenesis of HIV and HCV infections. Therefore, determining and manipulating these miRNAs can lead to opening a new gate to control these important infections.
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Affiliation(s)
- Mohsen Moghoofei
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sohrab Najafipour
- Department of Microbiology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Shayan Mostafaei
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ahmad Tavakoli
- Department of Virology, Faculty of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Farah Bokharaei-Salim
- Department of Virology, Faculty of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Saied Ghorbani
- Department of Virology, Faculty of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Davod Javanmard
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Hadi Ghaffari
- Department of Bacteriology and Virology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
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Vinhaes CL, Araujo-Pereira M, Tibúrcio R, Cubillos-Angulo JM, Demitto FO, Akrami KM, Andrade BB. Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV. Life (Basel) 2021; 11:life11010065. [PMID: 33477581 PMCID: PMC7831327 DOI: 10.3390/life11010065] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/13/2021] [Accepted: 01/14/2021] [Indexed: 12/19/2022] Open
Abstract
Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS.
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Affiliation(s)
- Caian L. Vinhaes
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Bahiana School of Medicine and Public Health, Bahia Foundation for the Development of Sciences, Salvador 40290-000, Brazil
| | - Mariana Araujo-Pereira
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil
| | - Rafael Tibúrcio
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil
| | - Juan M. Cubillos-Angulo
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil
| | - Fernanda O. Demitto
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
| | - Kevan M. Akrami
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil
- Divisions of Infectious Diseases and Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, CA 92093, USA
| | - Bruno B. Andrade
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; (C.L.V.); (M.A.-P.); (R.T.); (J.M.C.-A.); (K.M.A.)
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 40210-320, Brazil;
- Bahiana School of Medicine and Public Health, Bahia Foundation for the Development of Sciences, Salvador 40290-000, Brazil
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil
- Curso de Medicina, Centro Universitário Faculdade de Tecnologia e Ciências (UniFTC), Salvador 41741-590, Brazil
- Correspondence: ; Tel.: +55-71-3176-2264
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Efficacy and Tolerability of Daclatasvir/Sofosbuvir (Datex) in Patients with HIV-HCV Co-infection. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2020. [DOI: 10.5812/archcid.99952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents in patients with HCV/human immunodeficiency virus (HIV) co-infection remains controversial due to drug interactions with antiretroviral therapy (ART). Objectives: In this study, we assessed the efficacy and tolerability of daclatasvir/sofosbuvir (DCV/SOF) in patients with HIV-HCV co-infection in the real-life setting in Iran. Methods: A total of 44 patients with HCV-HIV co-infection (genotypes 1, 3, and 4) were treated with DCV/SOF±RBV (ribavirin) (dose-adjusted DCV for concomitant ART). Assessment of risk factors, sustained virologic response at 12 weeks after the end of treatment (SVR12), safety, and serum CD4 count was performed. Results: Most patients were male (95.2%). Four patients were HCV treatment-experienced cases, and 15 had cirrhosis or advanced fibrosis. The most common genotype was 3 (53.5%), followed by 1 (44.2%) and 4 (2.3%). HIV-1 RNA < 50 copies/mL and CD4 count > 250 cells/mm3 were observed in 81.8% and 79.1% of patients, respectively. The highest risk factor was a history of IV drug use (81.8%), followed by using a common syringe (77.3%) and tattooing (70.5%). All patients with or without cirrhosis (100%) completed the HCV treatment course and achieved SVR12. Also. 92.6% of patients on ART had CD4 count > 250 cells/mm3 at the end of treatment. The HCV treatment regimen was well-tolerated. Moreover, 15.9% of patients experienced adverse events (AEs), including anorexia, nausea, diarrhea, palpitations, and anxiety. No serious AEs or discontinuation due to AEs were reported. Conclusions: Our study showed excellent tolerability and efficacy of DCV/SOF±RBV in HIV-HCV co-infected patients with or without cirrhosis.
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De Pablo-Bernal RS, Jimenez-Leon MR, Tarancon-Diez L, Gutierrez-Valencia A, Serna-Gallego A, Trujillo-Rodriguez M, Alvarez-Rios AI, Milanes-Guisado Y, Espinosa N, Roca-Oporto C, Viciana P, Lopez-Cortes LF, Ruiz-Mateos E. Modulation of Monocyte Activation and Function during Direct Antiviral Agent Treatment in Patients Coinfected with HIV and Hepatitis C Virus. Antimicrob Agents Chemother 2020; 64:e00773-20. [PMID: 32571815 PMCID: PMC7449156 DOI: 10.1128/aac.00773-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 06/15/2020] [Indexed: 12/16/2022] Open
Abstract
The activation phenotypes and functional changes in monocyte subsets during hepatitis C virus (HCV) elimination in HIV/HCV-coinfected patients were evaluated. Twenty-two HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antiviral (DAA) therapy and 10 HIV-monoinfected patients were included. The activation phenotype (10 markers) and polyfunctionality (intracellular interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-10 production) in three monocyte subsets (classical, intermediate, and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV DNA levels were assayed by droplet digital PCR. After HCV clearance, there was a significant increase in classical monocyte and decreases in intermediate and nonclassical monocyte levels. The levels of the activation markers CD49d, CD40, and CX3CR1 were decreased after treatment in the monocyte subsets, reaching the levels in HIV-monoinfected patients. After lipopolysaccharide (LPS) stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations, such as the IL-1α- (IL-1α-negative) IL-1β- IL-6+ (IL-6-producing) IL-8- TNF-α- IL-10- combination, were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV DNA levels correlated with activation markers before but not after treatment. HCV clearance after DAA treatment in patients on cART exerts an anti-inflammatory profile on monocyte subsets, activation phenotypes, and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients.
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Affiliation(s)
- Rebeca S De Pablo-Bernal
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - M Reyes Jimenez-Leon
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Laura Tarancon-Diez
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Alicia Gutierrez-Valencia
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Ana Serna-Gallego
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Maria Trujillo-Rodriguez
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Ana I Alvarez-Rios
- Department of Clinical Biochemistry, Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Yusnelkis Milanes-Guisado
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Nuria Espinosa
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Cristina Roca-Oporto
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Pompeyo Viciana
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Luis F Lopez-Cortes
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
| | - Ezequiel Ruiz-Mateos
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, CSIC, University of Seville, Seville, Spain
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Bertol BC, Dias FC, Debortoli G, Souto BM, Mendonça PB, Araújo RC, Santana RC, Ramalho LNZ, Castelli EC, Martinelli ADLC, Mendes-Junior CT, Carosella ED, Donadi EA, Moreau P. HLA-G liver expression and HLA-G extended haplotypes are associated with chronic hepatitis C in HIV-negative and HIV-coinfected patients. Clin Immunol 2020; 217:108482. [PMID: 32470543 DOI: 10.1016/j.clim.2020.108482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 03/05/2020] [Accepted: 05/25/2020] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis C virus (HCV) infection induces liver damage and the HCV/Human Immunodeficiency Virus (HIV)-coinfection may further contribute to its progression. The HLA-G molecule inhibits innate and adaptive immunity and may be deleterious for chronically virus-infected cells. Thus we studied 204 HCV-mono-infected patients, 142 HCV/HIV-coinfected patients, 104 HIV-mono-infected patients and 163 healthy subjects. HLA-G liver expression was similarly induced in HCV and HCV/HIV specimens, increasing with advanced fibrosis and necroinflammatory activity, and with increased levels of liver function-related enzymes. Plasma soluble HLA-G (sHLA-G) levels were higher in HCV/HIV patients compared to HCV, HIV and to healthy individuals. sHLA-G continued to be higher in coinfected patients even after stratification of samples according to degree of liver fibrosis and necroinflammatory activity when compared to mono-infected patients. Some HLA-G gene haplotypes differentiated patient groups and presented few associations with liver and plasma HLA-G expression. HLA-G thus may help to distinguish patient groups.
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Affiliation(s)
- Bruna Cristina Bertol
- Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Fabrício César Dias
- Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil; Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France; Université Paris-Diderot, UMR 976 HIPI, Institut de Recherche Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France
| | - Guilherme Debortoli
- Postgraduate Program of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Bruno Mendes Souto
- Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Priscila Baptista Mendonça
- Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Roberta Chaves Araújo
- Department of Medicine, Division of Gastroenterology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Rodrigo Carvalho Santana
- Department of Medicine, Division of Infectious and Tropical Diseases, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900, Ribeirão Preto, Brazil
| | - Leandra Náira Zambelli Ramalho
- Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Erick Cruz Castelli
- São Paulo State University, Department of Pathology, School of Medicine, Av. Dr. Mario Rubens Guimarães Montenegro, 18618-687 Botucatu, Brazil
| | - Ana de Lourdes Candolo Martinelli
- Department of Medicine, Division of Gastroenterology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Celso Teixeira Mendes-Junior
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Edgardo Delfino Carosella
- Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France; Université Paris-Diderot, UMR 976 HIPI, Institut de Recherche Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France
| | - Eduardo Antônio Donadi
- Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil; Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, 14049-900 Ribeirão Preto, Brazil
| | - Philippe Moreau
- Commissariat à l'Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France; Université Paris-Diderot, UMR 976 HIPI, Institut de Recherche Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris, France.
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Morales MK, Lambing T, Husson J. Review: Evaluation and Management of the HIV/HCV Co-Infected Kidney or Liver Transplant Candidate. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020. [DOI: 10.1007/s40506-020-00220-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Reply to: Benefits of cannabis use for metabolic disorders and survival in people living with HIV with or without hepatitis C. AIDS 2020; 34:955-956. [PMID: 32271255 DOI: 10.1097/qad.0000000000002481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Epidemiological Features and Risk Factors for Acquiring Hepatitis B, Hepatitis C, and Syphilis in HIV-Infected Patients in Shaanxi Province, Northwest China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17061990. [PMID: 32197326 PMCID: PMC7143838 DOI: 10.3390/ijerph17061990] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 03/12/2020] [Accepted: 03/16/2020] [Indexed: 01/01/2023]
Abstract
Human immunodeficiency virus (HIV)-infected patients are at a higher risk for co-infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Treponema pallidum (TP; the agent causing syphilis) than the general population. The prevalence of HBV, HCV, and syphilis has geographic differences and varies from region to region among HIV-positive individuals. A retrospective study was carried out on HIV-positive individuals between June 2011 and June 2016 in Shaanxi Province. Univariate and multivariate logistic regression analyses using stepwise regression analysis regarding risk factors for HIV–HBV, HIV–HCV, and HIV–syphilis co-infection. HBV–HCV, HCV–syphilis, HBV–syphilis, and HBV–HCV–syphilis co-infection rates were 1.7%, 2.2%, 2.6%, and 0.1%, respectively. The rate of ineffective hepatitis B vaccine immunization was as high as 30.2% among HIV-positive individuals. Ethnicity (OR = 31.030, 95% CI: 11.643–82.694) and HIV transmission routes (OR = 134.024, 95% CI: 14.328–1253.653) were the risk factors for HCV infection in HIV-positive individuals. Among the HIV-positive individuals with the antibodies of TP, the rate of homosexual transmission was also higher, but heterosexual transmission was lower (OR = 0.549 95% CI: 0.382–0.789) The HIV-infected patients in Shaanxi Province had the characteristics of low active detection rate and late diagnosis. The high rate of ineffective vaccination against HBV suggests a need for improved vaccination services.
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Kardashian A, Peters MG, Tien PC, Price JC. The Pathogenesis of Liver Disease in People Living With Human Immunodeficiency Virus: The Emerging Role of the Microbiome. Clin Liver Dis (Hoboken) 2020; 15:46-51. [PMID: 32104578 PMCID: PMC7041953 DOI: 10.1002/cld.880] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/25/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Ani Kardashian
- Division of GastroenterologyDepartment of MedicineUniversity of California San FranciscoSan FranciscoCA
| | - Marion G. Peters
- Division of GastroenterologyDepartment of MedicineUniversity of California San FranciscoSan FranciscoCA
| | - Phyllis C. Tien
- Division of GastroenterologyDepartment of MedicineUniversity of California San FranciscoSan FranciscoCA,Medical ServiceDepartment of Veterans Affairs Medical CenterSan FranciscoCA
| | - Jennifer C. Price
- Division of GastroenterologyDepartment of MedicineUniversity of California San FranciscoSan FranciscoCA
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Leyna GH, Makyao N, Mwijage A, Ramadhan A, Likindikoki S, Mizinduko M, Leshabari MT, Moen K, Mmbaga EJ. HIV/HCV co-infection and associated risk factors among injecting drug users in Dar es Salaam, Tanzania: potential for HCV elimination. Harm Reduct J 2019; 16:68. [PMID: 31829199 PMCID: PMC6907336 DOI: 10.1186/s12954-019-0346-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 12/03/2019] [Indexed: 02/06/2023] Open
Abstract
Background Chronic HCV infection causes substantial morbidity and mortality and, in co-infection with HIV, may result in immunological and virological failure following antiretroviral treatment. Estimates of HCV infection, co-infection with HIV and associated risk practices among PWID are scarce in Africa. This study therefore aimed at estimating the prevalence of HCV and associated risk factors among PWID in the largest metropolitan city in Tanzania to inform WHO elimination recommendations. Methods An integrated bio-behavioral survey using respondent-driven sampling was used to recruit PWID residing in Dar es Salaam, Tanzania. Following face-to-face interviews, blood samples were collected for HIV and HCV testing. Weighted modified Poisson regression modeling with robust standard errors was used in the analysis. Results A total of 611 PWID with a median age of 34 years (IQR, 29–38) were recruited through 4 to 8 waves. The majority of participants (94.3%) were males, and the median age at first injection was 24 years (IQR, 19–30). Only 6.55% (40/611) of participants reported to have been enrolled in opioid treatment programs. The weighted HCV antibody prevalence was 16.2% (95%CI, 13.0–20.1). The corresponding prevalence of HIV infection was 8.7% (95%CI, 6.4–11.8). Of the 51 PWID who were infected with HIV, 22 (43.1%) were HCV seropositive. Lack of access to clean needles (adjusted prevalence ratio (APR), 1.76; 95%CI, 1.44; 12.74), sharing a needle the past month (APR, 1.72; 95%CI, 1.02; 3.00), not cleaning the needle the last time shared (APR, 2.29; 95%CI, 1.00; 6.37), and having unprotected not using a transactional sex (APR, 1.87; 95%CI, 1.00; 3.61) were associated with increased risk of HCV infection. On the other hand, not being on opioid substitution therapy was associated with 60% lower likelihood of infection. Conclusions The HCV antibody prevalence among PWID is lower than global estimates indicating potential for elimination. Improving access to safe injecting paraphernalia, promoting safer injecting practices is the focus of prevention programing. Screening for HIV/HCV co-infection should be intensified in HIV care, opioid substitution programs, and other point of care for PWID. Use of direct-acting antiretroviral treatment would accelerate the achievement of hepatitis infection elimination goal by 2030.
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Affiliation(s)
- Germana Henry Leyna
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania
| | - Neema Makyao
- Ministry of Health, Community Development, Gender, Elderly and Children, Dodoma, Tanzania
| | - Alexander Mwijage
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania
| | - Angela Ramadhan
- Ministry of Health, Community Development, Gender, Elderly and Children, Dodoma, Tanzania
| | - Samuel Likindikoki
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania
| | - Mucho Mizinduko
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania
| | - Melkizedeck Thomas Leshabari
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania
| | | | - Elia John Mmbaga
- Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, P.O. Box 65015, Dar es Salaam, Tanzania. .,University of Oslo, Oslo, Norway.
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Gabai CM, Moore MS, Penrose K, Braunstein S, Bocour A, Neaigus A, Winters A. Hepatitis C infection among men who have sex with men living with HIV in New York City, 2000-2015. Sex Transm Infect 2019; 96:445-450. [PMID: 31801894 DOI: 10.1136/sextrans-2019-054208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 11/13/2019] [Accepted: 11/25/2019] [Indexed: 12/09/2022] Open
Abstract
OBJECTIVES To calculate the rate of hepatitis C virus (HCV) among HIV-infected men who have sex with men (MSM) with no reported history of injection drug use (IDU), and to assess whether disparities exist in HIV/HCV coinfection by race/ethnicity and neighbourhood poverty level within this population in New York City. METHODS HIV-positive men who reported sex with men and did not report IDU at the time of HIV diagnosis, diagnosed through 2015 and alive as of 2000, were matched to people with HCV first reported to the New York City Department of Health and Mental Hygiene between 2000 and 2015. Those with HCV reported before or within 90 days of HIV infection were excluded. A multivariable Cox proportional hazards model was fit to compare the association between HCV diagnosis, race/ethnicity and neighbourhood poverty level. RESULTS From 2000 to 2015, 54 488 non-IDU MSM were diagnosed with HIV, of whom 2762 (5.1%) were diagnosed with HCV after HIV diagnosis, yielding an overall age-adjusted HCV diagnosis rate of 512 per 100 000 person-years. HIV/HCV coinfection was significantly higher among non-Latino blacks (adjusted HR (aHR)=1.24, 95% CI 1.11 to 1.40) compared with non-Latino whites and among persons living in high-poverty neighbourhoods compared with those in low-poverty neighbourhoods (aHR=1.17, 95% CI 1.01 to 1.35) after stratification by year of HIV diagnosis. CONCLUSION Disparities in HIV/HCV coinfection among HIV-positive MSM were observed by race/ethnicity and neighbourhood poverty level. Routine HCV screening is recommended for people infected with HIV. People coinfected with HIV and HCV should be linked to HCV care, treated and cured to reduce morbidity and mortality, and to avoid ongoing HCV transmission.
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Affiliation(s)
- Claudia Michelle Gabai
- Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USA.,Bureau of Communicable Disease, Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
| | - Miranda S Moore
- Bureau of Communicable Disease, Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
| | - Katherine Penrose
- HIV/AIDS Prevention and Control, Care and Treatment Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
| | - Sarah Braunstein
- HIV/AIDS Prevention and Control, Epidemiology and Field Services Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
| | - Angelica Bocour
- Bureau of Communicable Disease, Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
| | - Alan Neaigus
- Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USA
| | - Ann Winters
- Bureau of Communicable Disease, Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA
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Fu XH, Chen CZ, Wang Y, Peng YX, Wang WH, Yuan B, Gao Y, Jiang H, Zhang JB. COL1A1 affects apoptosis by regulating oxidative stress and autophagy in bovine cumulus cells. Theriogenology 2019; 139:81-89. [PMID: 31377650 DOI: 10.1016/j.theriogenology.2019.07.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 07/20/2019] [Accepted: 07/22/2019] [Indexed: 12/12/2022]
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