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Sun B, Abadjian L, Monto A, Freasier H, Pulliam L. Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms. J Infect Dis 2021; 222:396-406. [PMID: 32157304 DOI: 10.1093/infdis/jiaa109] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 03/05/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. METHODS We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy. RESULTS Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation. CONCLUSIONS Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.
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Affiliation(s)
- Bing Sun
- Department of Laboratory Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA
| | - Linda Abadjian
- Department of Mental Health, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA
| | - Alexander Monto
- Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.,University of California, San Francisco, San Francisco, California, USA
| | - Heather Freasier
- Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA
| | - Lynn Pulliam
- Department of Laboratory Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.,Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.,University of California, San Francisco, San Francisco, California, USA
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2
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Anthony DD, Sulkowski MS, Smeaton LM, Damjanovska S, Shive CL, Kowal CM, Cohen DE, Bhattacharya D, Alston-Smith BL, Balagopal A, Wyles DL. Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation. J Infect Dis 2020; 222:1334-1344. [PMID: 32406487 PMCID: PMC7749191 DOI: 10.1093/infdis/jiaa254] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 05/06/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. METHODS We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. RESULTS Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. CONCLUSIONS During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation. CLINICAL TRIALS REGISTRATION NCT02194998.
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Affiliation(s)
- Donald D Anthony
- Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland Ohio, USA
| | - Mark S Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Laura M Smeaton
- Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Sofi Damjanovska
- Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland Ohio, USA
| | - Carey L Shive
- Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland Ohio, USA
| | - Corinne M Kowal
- Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland Ohio, USA
| | | | - Debika Bhattacharya
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | | | - Ashwin Balagopal
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David L Wyles
- University of Colorado School of Medicine, Denver, Colorado, USA
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3
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Silva VCM, Calux SJ, Lemos MF, Compri AP, Santos APDT, Oba IT, Mendes-Correa MCJ, Moreira RC. Fluctuations in serological hepatitis C virus levels in HIV patients. Rev Soc Bras Med Trop 2019; 51:737-741. [PMID: 30517526 DOI: 10.1590/0037-8682-0239-2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 08/31/2018] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. METHODS We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. RESULTS We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. CONCLUSIONS Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.
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Affiliation(s)
| | - Samira Julien Calux
- Laboratório de Hepatites Virais, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, SP, Brasil
| | | | - Adriana Parise Compri
- Laboratório de Hepatites Virais, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, SP, Brasil
| | | | - Isabel Takano Oba
- Laboratório de Hepatites Virais, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, SP, Brasil
| | | | - Regina Célia Moreira
- Laboratório de Hepatites Virais, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, SP, Brasil
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4
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Judge CJ, Kostadinova L, Sherman KE, Butt AA, Falck-Ytter Y, Funderburg NT, Landay AL, Lederman MM, Sieg SF, Sandberg JK, Anthony DD. CD56 bright NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections. J Leukoc Biol 2017; 102:171-184. [PMID: 28400540 DOI: 10.1189/jlb.5a1116-456r] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 03/12/2017] [Accepted: 03/15/2017] [Indexed: 12/13/2022] Open
Abstract
Several lines of evidence support the concept that NK cells play an important role in control of hepatitis C virus (HCV) infection via cytokine secretion and cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development, activation, proliferation, and cytokine secretion. The IL-7Rα chain [cluster of differentiation (CD)127] is expressed on NK cells, with greatest abundance on the CD56brightCD16dim/- (CD56bright) subset. Here, we measured CD127 expression on CD56bright, CD56dimCD16+ (CD56dim), or CD56negCD16+ (CD56neg) NK cell subsets of 25 uninfected donors (UD); 34 chronic HCV-infected, treatment-naïve; 25 HIV-infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV-HIV-coinfected subjects on ART. Interestingly, CD127 expression on CD56bright NK cells negatively correlated with HCV plasma levels in HCV monoinfection and HCV-HIV coinfection. IL-7 induced CD69 expression, as well as IFN-γ production, in CD56bright NK cells and also enhanced the IFN-α-induced CD69 expression on these cells. The latter was impaired in HIV infection. Furthermore, IL-7 induced B cell lymphoma 2 (BCL-2) expression and cell cycling of CD56bright NK cells, and this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7-stimulated CD56bright NK cell degranulation appeared intact in all cohorts, we observed impaired IL-7-activated NK cell cytolytic function in HCV- and HIV-infected subjects. Finally, IL-7-induced phosphorylation of STAT-5 (pSTAT-5) signaling was impaired in NK cells of subjects with chronic viral infection, and this was reversible upon 6 mo of viral suppression with IFN-free HCV therapy. These results implicate that IL-7-dependent NK cell activation and effector function may be other host immune surveillance mechanisms that are impaired in viral infections.
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Affiliation(s)
- Chelsey J Judge
- Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.,Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
| | - Lenche Kostadinova
- Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
| | - Kenneth E Sherman
- Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
| | - Adeel A Butt
- Weill Cornell Medical College, New York, New York, USA.,Hamad Healthcare Quality Institute and Hamad Medical Corporation, Doha, Qatar
| | - Yngve Falck-Ytter
- Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.,Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
| | - Nicholas T Funderburg
- School of Health and Rehabilitation, Division of Medical Laboratory Science, The Ohio State University, Columbus, Ohio, USA
| | - Alan L Landay
- Rush University Medical Center, Chicago, Illinois, USA: and
| | - Michael M Lederman
- Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
| | - Scott F Sieg
- Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
| | - Johan K Sandberg
- Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Donald D Anthony
- Department of Pathology, Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA; .,Department of Medicine, University Hospitals Case Medical Center and Center for AIDS Research (CFAR), Case Western Reserve University, Cleveland, Ohio, USA
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5
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Kostadinova L, Shive CL, Judge C, Zebrowski E, Compan A, Rife K, Hirsch A, Falck-Ytter Y, Schlatzer DM, Li X, Chance MR, Rodriguez B, Popkin DL, Anthony DD. During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy. J Infect Dis 2016; 214:1438-1448. [PMID: 27540113 DOI: 10.1093/infdis/jiw372] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 08/09/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown. METHODS We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy. RESULTS We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes. CONCLUSIONS These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Daniel L Popkin
- Department of Dermatology, Cleveland VA Medical Center, University Hospitals Case Medical Center, Case Center for AIDS Research, Case Western Reserve University, Ohio
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6
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Liver involvement in human immunodeficiency virus infection. Indian J Gastroenterol 2016; 35:260-73. [PMID: 27256434 DOI: 10.1007/s12664-016-0666-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 05/01/2016] [Indexed: 02/04/2023]
Abstract
The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non-alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV-infected patients. Careful monitoring is required for drug interactions and drug-induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients.
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7
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Puri P, Saraswat VA, Dhiman RK, Anand AC, Acharya SK, Singh SP, Chawla YK, Amarapurkar DN, Kumar A, Arora A, Dixit VK, Koshy A, Sood A, Duseja A, Kapoor D, Madan K, Srivastava A, Kumar A, Wadhawan M, Goel A, Verma A, Shalimar, Pandey G, Malik R, Agrawal S. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016. J Clin Exp Hepatol 2016; 6:119-145. [PMID: 27493460 PMCID: PMC4963318 DOI: 10.1016/j.jceh.2016.07.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.
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Key Words
- ALT, alanine aminotransferase
- ANC, absolute neutrophil count
- AST, aspartate aminotransferase
- CH-C, chronic hepatitis C
- CTP, Child-Turcotte-Pugh
- DAA, directly acting antiviral agents
- DCV, daclatasvir
- EIA, enzyme immunoassay
- ESRD, end-stage renal disease
- EVR, early virological response
- FCH, fibrosing cholestatic hepatitis
- GT, genotype
- HCV
- HCV, hepatitis C virus
- HCWs, healthcare workers
- HIV, human immunodeficiency virus
- INASL, Indian National Association for Study of the Liver
- IU, international units
- LDV, ledipasvir
- LT, liver transplantation
- NS, nonstructural protein
- NSI, needlestick injury
- PCR, polymerase chain reaction
- Peg-IFNα, pegylated interferon alfa
- RBV, ribavirin
- RVR, rapid virological response
- SOF, sofosbuvir
- SVR, sustained virological response
- ULN, upper limit of normal
- anti-HCV, antibody to HCV
- antiviral therapy
- chronic hepatitis
- hepatitis C virus
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Affiliation(s)
- Pankaj Puri
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi 110076, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack 753007, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | | | - Ajay Kumar
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Banaras Hindu University, Varanasi 221005, India
| | - Abraham Koshy
- Department of Hepatology, Lakeshore Hospital, Cochin 682304, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana 141001, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad 500004, India
| | - Kaushal Madan
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122001, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Manav Wadhawan
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Abhai Verma
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Gaurav Pandey
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Rohan Malik
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Swastik Agrawal
- Department of Gastroenterology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, India
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Ogishi M, Yotsuyanagi H, Tsutsumi T, Gatanaga H, Ode H, Sugiura W, Moriya K, Oka S, Kimura S, Koike K. Deconvoluting the composition of low-frequency hepatitis C viral quasispecies: comparison of genotypes and NS3 resistance-associated variants between HCV/HIV coinfected hemophiliacs and HCV monoinfected patients in Japan. PLoS One 2015; 10:e0119145. [PMID: 25748426 PMCID: PMC4351984 DOI: 10.1371/journal.pone.0119145] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Accepted: 01/09/2015] [Indexed: 12/16/2022] Open
Abstract
Pre-existing low-frequency resistance-associated variants (RAVs) may jeopardize successful sustained virological responses (SVR) to HCV treatment with direct-acting antivirals (DAAs). However, the potential impact of low-frequency (∼0.1%) mutations, concatenated mutations (haplotypes), and their association with genotypes (Gts) on the treatment outcome has not yet been elucidated, most probably owing to the difficulty in detecting pre-existing minor haplotypes with sufficient length and accuracy. Herein, we characterize a methodological framework based on Illumina MiSeq next-generation sequencing (NGS) coupled with bioinformatics of quasispecies reconstruction (QSR) to realize highly accurate variant calling and genotype-haplotype detection. The core-to-NS3 protease coding sequences in 10 HCV monoinfected patients, 5 of whom had a history of blood transfusion, and 11 HCV/HIV coinfected patients with hemophilia, were studied. Simulation experiments showed that, for minor variants constituting more than 1%, our framework achieved a positive predictive value (PPV) of 100% and sensitivities of 91.7–100% for genotyping and 80.6% for RAV screening. Genotyping analysis indicated the prevalence of dominant Gt1a infection in coinfected patients (6/11 vs 0/10, p = 0.01). For clinical samples, minor genotype overlapping infection was prevalent in HCV/HIV coinfected hemophiliacs (10/11) and patients who experienced whole-blood transfusion (4/5) but none in patients without exposure to blood (0/5). As for RAV screening, the Q80K/R and S122K/R variants were particularly prevalent among minor RAVs observed, detected in 12/21 and 6/21 cases, respectively. Q80K was detected only in coinfected patients, whereas Q80R was predominantly detected in monoinfected patients (1/11 vs 7/10, p < 0.01). Multivariate interdependence analysis revealed the previously unrecognized prevalence of Gt1b-Q80K, in HCV/HIV coinfected hemophiliacs [Odds ratio = 13.4 (3.48–51.9), p < 0.01]. Our study revealed the distinct characteristics of viral quasispecies between the subgroups specified above and the feasibility of NGS and QSR-based genetic deconvolution of pre-existing minor Gts, RAVs, and their interrelationships.
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Affiliation(s)
- Masato Ogishi
- Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
- * E-mail:
| | - Takeya Tsutsumi
- Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
| | - Hiroyuki Gatanaga
- AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Hirotaka Ode
- Department of Infectious Diseases and Immunology, Clinical Research Center, Nagoya Medical Center, Nagoya, Japan
| | - Wataru Sugiura
- Department of Infectious Diseases and Immunology, Clinical Research Center, Nagoya Medical Center, Nagoya, Japan
| | - Kyoji Moriya
- Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
| | - Shinichi Oka
- AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
| | - Satoshi Kimura
- Director, Tokyo Teishin Hospital, Tokyo, Japan; President, Tokyo Health Care University, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan
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Plasma proteome analysis reveals overlapping, yet distinct mechanisms of immune activation in chronic HCV and HIV infections. J Acquir Immune Defic Syndr 2013; 63:563-71. [PMID: 23507661 DOI: 10.1097/qai.0b013e3182909847] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND HIV infection contributes to accelerated rates of progression of liver fibrosis during hepatitis C virus (HCV) infection, and HCV liver disease contributes to mortality during HIV infection. Although mechanisms underlying these interactions are not well known, soluble and cellular markers of immune activation associate with disease progression during both infections. METHODS We identified proteins varying in expression across the plasma proteomes of subjects with untreated HIV infection, untreated HCV infection with low aspartate transaminase/platelet ratio index, untreated HCV infection with high aspartate transaminase/platelet ratio index, HIV-HCV coinfection, and controls. We examined correlations between dysregulated proteins and markers of immune activation to uncover biomarkers specific to disease states. RESULTS We observed the anticipated higher frequencies of HLA-DRCD38CD4 and CD8 T cells, higher serum soluble CD14 levels, and higher serum interleukin-6 levels for HCV- and HIV-infected groups compared with controls. Plasma proteome analysis identified 2297 peptides mapping to 227 proteins, and quantitative analysis of peptide intensity identified significant changes in 85 proteins across the 5 groups. Abundance for 7 of these proteins was validated by enzyme-linked immunosorbent assay. Forty-three of these proteins correlated with markers of immune activation, including at least 2 proteins that may directly drive T-cell activation. As a functional validation, we tested the enzymatic pathway product (lysophosphatidic acid, LPA) of one such protein, ecotonucleotide pyrophosphatase/phosphodiesterase-2, for ability to activate T cells in vitro. LPA activated T cells to express CD38 and HLA-DR. CONCLUSIONS These data indicate that elevated levels of ecotonucleotide pyrophosphatase/phosphodiesterase-2 and LPA during advanced HCV disease may play a role in exacerbating immune activation during HCV-HIV coinfection.
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Ravasio R. Costo efficacia di peginterferone α-2a + ribavirina versus peginterferone α-2b + ribavirina nel trattamento dell’epatite cronica di tipo C in pazienti HIV co-infetti. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/bf03320639] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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11
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Bhunu C, Mushayabasa S. Modelling the transmission dynamics of HIV/AIDS and hepatitis C virus co-infection. HIV & AIDS REVIEW 2013. [DOI: 10.1016/j.hivar.2013.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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12
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Schmidt WN, Mathahs MM, Zhu Z. Heme and HO-1 Inhibition of HCV, HBV, and HIV. Front Pharmacol 2012; 3:129. [PMID: 23060790 PMCID: PMC3463857 DOI: 10.3389/fphar.2012.00129] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Accepted: 06/18/2012] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative products, and related compounds of the heme oxygenase system inhibit replication of all 3 viruses. The purpose of this review is to critically evaluate and summarize the seminal studies that described and characterized this remarkable behavior. It will also discuss more recent work that discovered the antiviral mechanisms and target sites of these unique antiviral agents. In spite of the fact that these viruses are diverse pathogens with quite profound differences in structure and life cycle, it is significant that heme and related compounds show striking similarity for viral target sites across all three species. Collectively, these findings strongly indicate that we should move forward and develop heme and related tetrapyrroles into versatile antiviral agents that could be used therapeutically in patients with single or multiple viral infections.
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Affiliation(s)
- Warren N Schmidt
- Department of Internal Medicine and Research Service, Veterans Affairs Medical Center, University of Iowa Iowa City, IA, USA ; Department of Internal Medicine, Roy G. and Lucille A. Carver College of Medicine, University of Iowa Iowa City, IA, USA
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13
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Yami A, Alemseged F, Hassen A. Hepatitis B and C Viruses Infections and Their Association with Human Immunodeficiency Virus: A Cross-Sectional Study among Blood Donors in Ethiopia. Ethiop J Health Sci 2012; 21:67-75. [PMID: 22434987 PMCID: PMC3275856 DOI: 10.4314/ejhs.v21i1.69047] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Background Since the introduction of Highly Active Anti-Retroviral Therapy and the dramatic improvement in the prognosis of individuals with Human Immunodeficiency Virus, liver disease due to chronic viral hepatitis has become as important cause of morbidity and mortality in co-infected individuals. The objective of the study was to determine the Sero-prevalence of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus and the association of the virus with Hepatitis B Virus and Hepatitis C Virus infection. As Human Immunodeficiency Virus and Hepatitis B Virus infections are highly prevalent and they are among the major public health concern in developing countries including Ethiopia investigating this problem is of paramount benefit. Although studies on co-infection of Hepatitis C Virus and Human Immunodeficiency Virus have clearly identified adverse effects of co-infection, the prevalence of Hepatitis C Virus infection and the association with Human Immunodeficiency Virus in developing countries including Ethiopia has not been know for sure. Method A cross sectional study was conducted from January 1 to 31, 2010, in Jimma University specialized hospital Blood Bank. The inclusion criteria of the study was adult who donated blood to Jimma University specialized hospital blood bank any time from establishment of the unit until January 2010 and whose record was retrieved. Accordingly 9,204 adults were included of which 6,063 were selected by lottery method. Data on socio-demographic variables (age and sex), laboratory test result for Hepatitis B surface Antigen, anti-Hepatitis C Virus antibody, anti-Human Immunodeficiency Virus 1 antibody, and Rapid Plasma Reagin tests were collected using structured questionnaire. After the data were collected, they were entered into a computer and analyzed using SPSS -16 for windows. P-Value of < 0.05 was taken to be statistically significant. Results The prevalence rate of Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus and syphilis infection were 2.1%, 0.2%, 2.1% and 0.7%, respectively. Sex and age had statistically significant association with Human Immunodeficiency and Hepatitis B virus infections where females were less likely to be infected. As age increases above 20 years, the risk of infection with Human Immunodeficiency Virus or Hepatitis B Virus increases. There was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus. Conclusion the prevalence rate of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus infections among blood donors in Jimma University specialized hospital were lower as compared to previous studies, in addition there was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus. Thus, community based study should be conducted to confirm the relationship of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus.
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BHUNU CP, MUSHAYABASA S. ASSESSING THE EFFECTS OF INTRAVENOUS DRUG USE ON HEPATITIS C TRANSMISSION DYNAMICS. J BIOL SYST 2011. [DOI: 10.1142/s0218339011004056] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
A mathematical model for the transmission dynamics of Hepatitis C virus (HCV) have been proposed and investigated. The model presented looks into preferential sexual contacts between intravenous drug users and non-drug users. The threshold parameters of the model are determined and stabilities analysed. Both analytic and numerical simulations show that increase in intravenous drug use in addition to sex results in an increase of HCV cases. Thus, safe sex and treatment of HCV alone are not enough to curtail the transmission of HCV. Effective control of HCV require strategies that are tailor made for intravenous drug users.
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Affiliation(s)
- C. P. BHUNU
- Department of Mathematics, University of Zimbabwe, Box MP 167 Mount Pleasant, Harare, Zimbabwe
- Department of Veterinary Medicine, University of Cambridge, CB3, OES, UK
| | - S. MUSHAYABASA
- Department of Applied Mathematics, Modelling Biomedical Systems Research Group, National University of Science and Technology, Box AC 939 Ascot, Bulawayo, Zimbabwe
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15
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Dominguez S, Ghosn J, Peytavin G, Guiguet M, Tubiana R, Valantin MA, Murphy R, Bricaire F, Benhamou Y, Katlama C. Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study. J Antimicrob Chemother 2010; 65:2445-9. [DOI: 10.1093/jac/dkq320] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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16
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Kabinda JM, Katchunga BP. Les hépatites virales B et C chez les porteurs du virus de l’immunodéficience humaine à Bukavu (Sud-Kivu), République démocratique du Congo. ACTA ACUST UNITED AC 2010. [DOI: 10.1007/s12157-010-0204-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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17
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Modjarrad K, Vermund SH. Effect of treating co-infections on HIV-1 viral load: a systematic review. THE LANCET. INFECTIOUS DISEASES 2010; 10:455-63. [PMID: 20610327 DOI: 10.1016/s1473-3099(10)70093-1] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Co-infections contribute to HIV-related pathogenesis and often increase viral load in HIV-infected people. We did a systematic review to assess the effect of treating key co-infections on plasma HIV-1-RNA concentrations in low-income countries. We identified 18 eligible studies for review: two on tuberculosis, two on malaria, six on helminths, and eight on sexually transmitted infections, excluding untreatable or non-pathogenic infections. Standardised mean plasma viral load decreased after the treatment of co-infecting pathogens in all 18 studies. The standardised mean HIV viral-load difference ranged from -0.04 log(10) copies per mL (95% CI -0.24 to 0.16) after syphilis treatment to -3.47 log(10) copies per mL (95% CI -3.78 to -3.16) after tuberculosis treatment. Of 14 studies with variance data available, 12 reported significant HIV viral-load differences before and after treatment. Although many of the viral-load reductions were 1.0 log(10) copies per mL or less, even small changes in plasma HIV-RNA concentrations have been shown to slow HIV progression and could translate into population-level benefits in lowering HIV transmission risk.
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Affiliation(s)
- Kayvon Modjarrad
- Department of Medicine, Vanderbilt University School of Medicine, Medical Center, 2525 West End Avenue, Nashville, TN, USA.
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18
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Bova C, Ogawa LF, Sullivan-Bolyai S. Hepatitis C treatment experiences and decision making among patients living with HIV infection. J Assoc Nurses AIDS Care 2009; 21:63-74. [PMID: 19853480 DOI: 10.1016/j.jana.2009.07.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Accepted: 07/16/2009] [Indexed: 12/18/2022]
Abstract
Hepatitis C infection is a major problem for approximately 250,000 HIV-infected persons in the United States. Although HIV infection is well-controlled in most of this population, they suffer liver-associated morbidity and mortality. Conversely, hepatitis C virus (HCV) treatment uptake remains quite low (15%-30%). Therefore, the purpose of this qualitative study was to explore HCV treatment experiences and decision making in adults with HIV infection. The study sample included 39 coinfected adults; 16 in the HCV-treated cohort (who were interviewed a maximum of 3 times) and 23 in the HCV-nontreatment cohort. Analysis of interviews identified 2 treatment barriers (fears and vicarious experiences) and 4 facilitating factors (experience with illness management, patient-provider relationships, gaining sober time, and facing treatment head-on). Analysis of these data also revealed a preliminary model to guide intervention development and theoretical perspectives. Ultimately, research is urgently needed to test interventions that improve HCV evaluation and treatment uptake among HIV-infected patients.
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Abstract
HIV infection has become a global disease, both in geographic terms, since it has spread worldwide, and at the individual level since it affects every organ of the human body. Antiretroviral treatments, in countries where they are easily available, have modified HIV infection into a systemic chronic disease, the life expectancy of which is yet to be determined precisely. Treatments have dramatically changed the pattern of the disease and clinicians now have to face a number of new challenges. Kidneys, like all the other organs, can be involved in a great number of diseases in HIV-infected patients. We have voluntarily chosen to present "kidney diseases in HIV-infected patients" in their wider meaning, with a discussion of renal diseases that are directly caused by the virus, nephropathies due to frequent viral co-infections in HIV-infected patients such as HCV and HBV, nephropathies induced by anti-HIV, HBV and HCV therapies. Physicians in charge of HIV-infected patients should be aware of the key role they have to play in the screening for kidney abnormalities. This participates not only in improving patients' kidney prognosis but also their long-term general outcome. Renal screening strategies must refer to simple routine laboratory tests. Enclosed at the end of this article are a few suggestions for the renal management of situations that frequently occur in HIV infected patients (kidney dysfunction screening, serum creatinine increase and discovery of a proteinuria).
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20
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Ingiliz P, Valantin MA, Duvivier C, Medja F, Dominguez S, Charlotte F, Tubiana R, Poynard T, Katlama C, Lombès A, Benhamou Y. Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy. Hepatology 2009; 49:436-42. [PMID: 19085967 DOI: 10.1002/hep.22665] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
UNLABELLED Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m(2), HIV RNA: 200 copies/mL, CD4 count: 365/mm(3), duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. CONCLUSIONS HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance.
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Affiliation(s)
- Patrick Ingiliz
- Hepatology Department, AP-HP, GH Pitié-Salpêtrière, Paris, France.
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21
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Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 2008; 113:4086-93. [PMID: 19023115 DOI: 10.1182/blood-2008-09-181073] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP) have a unique Ab against platelet GPIIIa49-66 capable of inducing oxidative platelet fragmentation in the absence of complement. HIV-1-seropositive drug abusers are more prone to develop immune thrombocytopenia than non-drug abusers and have a higher coinfection with hepatitis C virus (HCV) than non-drug abusers (90% vs 30%). Molecular mimicry was sought by screening a phage peptide library with anti-GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV. Several phage peptide clones had 70% homology with HCV protein. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with 4 nonconserved peptides from HCV core envelope 1. Reactivity correlated inversely with platelet count (r(2) = 0.7, P < .01). Ab raised against peptide PHC09 in GPIIIa(-/-) mice induced thrombocytopenia in wild-type mice. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro. Drug abusers dually infected with HCV and HIV-1 had a greater incidence and severity of thrombocytopenia as well as titer of anti-GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab versus PHC09 and significantly decreased their platelet count (P < .001). Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66.
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22
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Wu FB, Ouyan HQ, Tang XY, Zhou ZX. Double-antigen sandwich time-resolved immunofluorometric assay for the detection of anti-hepatitis C virus total antibodies with improved specificity and sensitivity. J Med Microbiol 2008; 57:947-953. [PMID: 18628493 DOI: 10.1099/jmm.0.47835-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Current anti-hepatitis C virus (HCV) antibody screening immunoassays are routinely based on an indirect format. Although their use for anti-HCV antibody detection has achieved a very high specificity and sensitivity, false-positive results are still a problem especially among populations with a low prevalence of HCV infection. One strategy to obviate this problem is to adapt the assay from an indirect format to a double-antigen sandwich one to further improve its specificity. In this study, a double-antigen sandwich time-resolved immunofluorometric assay (DAS-TRIFMA) has been developed to detect total anti-HCV antibodies based on biotin-streptavidin interaction. For comparison, 1025 samples were analysed by the DAS-TRIFMA and three indirect anti-HCV antibody detection methods. For samples with discordant results, PCR-ELISA and Inno-LIA were employed as supplementary assays to analyse the presence of HCV antibodies. With regard to the 1025 clinical samples, the overall concordance between the DAS-TRIFMA and the three indirect methods was 99.41, 98.93 and 98.93 % for Ortho ELISA 3.0, WAT ELISA and I-TRIFMA, respectively. The specificity/sensitivity of the DAS-TRIFMA, Ortho HCV ELISA 3.0, WAT HCV ELISA and I-TRIFMA were 100/99.09, 99.34/98.18, 99.23/97.27 and 99.01 %/98.18 %, respectively. The DAS-TRIFMA was able to detect HCV antibodies at a concentration about 1/10 of that detectable by indirect methods. From the obtained results and their comparison, it is concluded that the DAS-TRIFMA is a more specific and reliable method for screening anti-HCV antibodies, and weakly positive S/Co values by the DAS-TRIFMA were more predictive of HCV infection than those by indirect methods.
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Affiliation(s)
- Feng-Bo Wu
- Research & Development Department, SYM-BIO Life-Science Co. Ltd, Tai-Cang City, Jiang-Su Province 215400, PR China
| | - Hai-Qiao Ouyan
- Research & Development Department, SYM-BIO Life-Science Co. Ltd, Tai-Cang City, Jiang-Su Province 215400, PR China
| | - Xiao-Yan Tang
- Research & Development Department, SYM-BIO Life-Science Co. Ltd, Tai-Cang City, Jiang-Su Province 215400, PR China
| | - Zhen-Xian Zhou
- Clinical Laboratory, Nanjing Second Hospital, Nanjing City 210003, PR China
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23
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Kritz S, Brown LS, Goldsmith RJ, Bini EJ, Robinson J, Alderson D, Novo P, Rotrosen J. States and substance abuse treatment programs: funding and guidelines for infection-related services. Am J Public Health 2008; 98:824-6. [PMID: 18381995 DOI: 10.2105/ajph.2007.119578] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Community-based substance abuse treatment programs provide HIV, hepatitis C virus, and sexually transmitted infection services. To explore how state funding and guidelines affect practice, we surveyed state agency administrators and substance abuse treatment program administrators and clinicians regarding 8 infection-related services. Although state funding for infection-related services is widely available, substance abuse treatment programs do not always access it. Substance abuse treatment program guidelines are clearer in states that have written guidelines. Improved communication between state agencies and substance abuse treatment programs may enhance service.
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Affiliation(s)
- Steven Kritz
- Addiction Research and Treatment Corporation, 22 Chapel St, Brooklyn, NY 11201, USA.
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24
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Carvalho-Filho RJ, Schiavon LL, Narciso-Schiavon JL, Sampaio JP, Lanzoni VP, Ferraz MLG, Silva AEB. Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection. Liver Int 2008; 28:486-493. [PMID: 18339075 DOI: 10.1111/j.1478-3231.2008.01675.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIM To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. PATIENTS AND METHODS This retrospective cross-sectional study included consecutive patients with HIV/HCV co-infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS One hundred and eleven patients were included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index < 0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. CONCLUSION APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co-infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.
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Affiliation(s)
- Roberto J Carvalho-Filho
- Division of Gastroenterology-Hepatitis Section, Federal University of Sao Paulo, Sao Paulo, Brazil.
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25
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Shen F, Huang Q, Sun HQ, Ghildyal R. Significance of blood analysis in hemophiliacs co-infected with human immunodeficiency virus and hepatitis viruses. World J Gastroenterol 2007; 13:1862-6. [PMID: 17465482 PMCID: PMC4149968 DOI: 10.3748/wjg.v13.i12.1862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of hepatitis virus infection on cirrhosis and liver function markers in HIV-infected hemophiliacs.
METHODS: We have analyzed the immunological, liver function and cirrhosis markers in a cohort of hemophiliacs co-infected with human immunodeficiency virus (HIV) and hepatitis viruses.
RESULTS: There was no difference in immunological markers among co-infected patients and patients infected with HIV only and those co-infected with one or more hepatitis virus. Although liver function and cirrhosis markers remained within a normal range, there was a worsening trend in all patients co-infected with hepatitis virus C (HCV), which was further exacerbated in the presence of additional infection with hepatitis virus B (HBV).
CONCLUSION: Co-infection with HIV, HBV and HCV leads to worsening of hyaluronic acid and liver function markers. Increases in serum hyaluronic acid may be suggestive of a predisposition to liver diseases.
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Affiliation(s)
- Fang Shen
- Shanghai Medical College and Shanghai Public Health Center, Fudan University, Shanghai 201508, China
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26
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Brown LS, Kritz SA, Goldsmith RJ, Bini EJ, Rotrosen J, Baker S, Robinson J, McAuliffe P. Characteristics of substance abuse treatment programs providing services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections: the National Drug Abuse Treatment Clinical Trials Network. J Subst Abuse Treat 2006; 30:315-21. [PMID: 16716846 PMCID: PMC2535811 DOI: 10.1016/j.jsat.2006.02.006] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2005] [Revised: 02/16/2006] [Accepted: 02/21/2006] [Indexed: 10/24/2022]
Abstract
Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the "Infections and Substance Abuse" study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy.
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Affiliation(s)
- Lawrence S Brown
- Addiction Research and Treatment Corporation, 22 Chapel St, Brooklyn, NY 11201, USA.
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27
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Jouvencel AC, Neau D, Faure M, Neau M, Martinaud C, Legrand E, Trimoulet P, Garrigue I, Le Bail B, Bioulac-Sage P, Dupon M, Ragnaud JM, Fleury H, Lafon ME. Plasma and liver hepatitis C virus variability in patients coinfected with human immunodeficiency virus. J Clin Microbiol 2006; 44:1877-80. [PMID: 16672429 PMCID: PMC1479191 DOI: 10.1128/jcm.44.5.1877-1880.2006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Liver and plasma hepatitis C virus (HCV) variability was compared by E2 cloning and sequencing in three patients coinfected with HCV and human immunodeficiency virus (HIV) before and after interferon treatment and in three patients solely infected with HCV. The plasma and liver samples contained unique sequences. In the patients coinfected with HIV, accumulated random mutations produced mostly nonsynonymous substitutions in contrast to the reduced HCV genetic variability seen after treatment.
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Affiliation(s)
- Anne-Christine Jouvencel
- Laboratoire de Virologie EA2968, Universite Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux, France
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28
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Silva ACM, Barone AA. [Risk factors for HIV infection among patients infected with hepatitis C virus]. Rev Saude Publica 2006; 40:482-8. [PMID: 16810373 DOI: 10.1590/s0034-89102006000300017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Human immunodeficiency virus and hepatitis C virus share the same routes of transmission. Currently, there is a high frequency of co-infection worldwide, especially among users of injectable drugs and in subjects with history of blood transfusions. The aim of the present study was to evaluate risk factors associated to human immunodeficiency virus infection in patients infected with hepatitis C virus. METHODS We carried out an epidemiological case-control study, including 118 patients (cases) infected by both viruses and 233 patients (controls) infected only by the hepatitis C virus. Between January 1999 and November 2001, patients responded to a questionnaire assessing sociodemographic and professional characteristics, and major risk factors for virus infection. After description and initial comparison, variables were evaluated by univariate analysis and then by multivariate logistic regression for variables selected through the maximum likelihood test. RESULTS Co-infection was associated with female sex (OR = 2.89; 95% CI: 1.16-7.08), being divorced/widow (OR = 3.91; 95% CI: 1.34-11.35), past or current use of illegal drugs (OR = 3.96; 95% CI: 1.55-10.13) and to the habit of sharing pipes or needles (OR = 10.28; 95% CI: 4.00-6.42). CONCLUSIONS Among patients infected with hepatitis C virus, female sex is a risk factor for HIV infection after adjustment for the habit of sharing pipes and needles. Being divorced/widow, use of illegal drugs, and the habit of sharing pipes and syringes were associated to co-infection.
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Affiliation(s)
- Anita Campos Mendonça Silva
- Divisão de Clínica de Moléstias Infecciosas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
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Bruno R, Sacchi P, Maiocchi L, Patruno S, Filice G. Hepatotoxicity and antiretroviral therapy with protease inhibitors: A review. Dig Liver Dis 2006; 38:363-73. [PMID: 16631422 DOI: 10.1016/j.dld.2006.01.020] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2005] [Revised: 12/28/2005] [Accepted: 01/25/2006] [Indexed: 12/11/2022]
Abstract
Highly active antiretroviral therapy including protease inhibitors has led to dramatic decrease in the morbidity and mortality resulting from infection with human immunodeficiency virus-1. However, this combination regimen can be associated with the occurrence of serious toxicities, which may reduce patient compliance. In particular, human immunodeficiency virus-1 protease inhibitors and nevirapine among nonnucleoside reverse transcriptase inhibitors, have the potential for producing hepatotoxicity. We summarise current knowledge of the hepatotoxic effects associated with the commercially available human immunodeficiency virus-1 protease inhibitors based on a literature review of the major retrospective and prospective clinical studies designed to elucidate risk factors for developing hepatotoxicity among human immunodeficiency virus-1-infected patients receiving antiretroviral therapy containing protease inhibitors. Coinfection with chronic hepatitis, a common occurrence in human immunodeficiency virus-1-infected patients, is identified as an independent risk factor for developing hepatotoxicity in antiretroviral-treated human immunodeficiency virus-1-infected patients treated with antiretroviral regimens containing protease inhibitors. The importance of other risk factors for developing protease inhibitor-associated hepatotoxicity and the mechanism underlying the drug-related hepatotoxicity are discussed. The data indicate that the potential for producing hepatotoxicity is variable among the protease inhibitors and suggest that based on differences in drug-related hepatotoxicity, certain protease inhibitors may be preferred for the treatment of human immunodeficiency virus-hepatitis C virus coinfected patients.
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Affiliation(s)
- R Bruno
- Division of Infectious and Tropical Disease, IRCCS S. Matteo Hospital, University of Pavia, 27100 Pavia, Italy.
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Vallet-Pichard A, Pol S. Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. J Hepatol 2006; 44:S28-34. [PMID: 16343684 DOI: 10.1016/j.jhep.2005.11.008] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Co-infection by the hepatitis C virus (HCV) is observed in up to 30% of HIV-infected individuals. In studies conducted in the 'pre-HAART era', the late consequences of HCV-related chronic liver disease were overshadowed by extra-hepatic causes of deaths, related to severe immune deficiency, and the impact of HCV infection on mortality of HIV-infected patients was low. While the development of HAART has resulted in a significant decrease in morbidity and mortality amongst HIV-infected patients, this clear benefit allowed the expression of liver-related complications associated with HCV chronic infection. The impact of HCV on HIV remains debated but HIV infection significantly modifies the natural history of HCV infection. HIV infection increases levels of HCV viraemia by 2- to 8-fold, resulting in a significant decrease in spontaneous recovery of acute hepatitis. HIV co-infection also worsens the histological course of HCV infection by increasing and accelerating the risk of cirrhosis or leading to rare but lethal fibrosing cholestatic hepatitis. Liver disease is now one of the leading causes of morbidity and mortality in co-infected patients, even if HAART and especially protease inhibitors, may decrease the severity of the liver disease and the liver-related mortality. Several non-exclusive pathogenic processes explain the increasing rate of liver complications associated with HCV-related liver disease.
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Affiliation(s)
- Anaïs Vallet-Pichard
- Inserm U-370 et Unité d'Hépatologie, Hôpital Necker; Faculté Paris V, 149 Rue de Sèvres, 75015 Paris, France
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31
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Cacoub P, Saadoun D, Limal N, Léger JM, Maisonobe T. Hepatitis C virus infection and mixed cryoglobulinaemia vasculitis: a review of neurological complications. AIDS 2005; 19 Suppl 3:S128-34. [PMID: 16251808 DOI: 10.1097/01.aids.0000192081.33938.2f] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic liver disease caused by hepatitis C virus (HCV) infection is commonly associated with extrahepatic manifestations, mainly mixed cryoglobulinaemia. Neurological complications in HCV-infected patients occur predominantly in the peripheral nervous system. Peripheral neuropathy in HCV infection is primarily associated with mixed cryoglobulinaemia. Central nervous system (CNS) involvement is more rarely reported. In this review, peripheral and CNS involvement associated with chronic HCV infection are described. The underlying mechanisms and treatment possibilities are discussed.
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Affiliation(s)
- Patrice Cacoub
- Department of Internal Medicine, Hôpital La Pitié-Salpêtrière, Paris, France.
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Abstract
BACKGROUND & AIMS The inclusion of protease inhibitors in 3-drug highly active antiretroviral regimens for treating patients who are infected with human immunodeficiency virus-1 has had a significant impact in increasing survival and decreasing morbidity. However, the effectiveness of this class of drugs may be compromised by the occurrence of drug-related hepatotoxicity, which is problematic especially in individuals co-infected with hepatitis viruses. Based on its clinical and pharmacologic profile, especially its unique pattern of resistance, nelfinavir has been used frequently as a first-line protease-inhibitor therapy for human immunodeficiency virus-1-infected patients. The aim of this study was to identify the relative potential for developing hepatotoxicity for nelfinavir vs other protease inhibitors. METHODS An exploratory meta-analysis of liver enzyme level increases was conducted in a combined total of 4268 patients derived from 3 large recently conducted prospective and retrospective clinical trials and a prospective cohort study. RESULTS The results indicate that among 4 commercially available protease inhibitors and a 2-protease inhibitor combination, nelfinavir and indinavir are associated with the lowest rates of occurrence of severe hepatotoxicity (ie, combined estimates of liver enzyme level increases of 2.9% and 3.1%, respectively). The low rate of occurrence of severe hepatotoxicity for nelfinavir was shown even among patients co-infected with hepatitis viruses. CONCLUSIONS In conclusion, these data provide support for the conclusion that differences in the potential for hepatotoxicity do exist among the commercially available protease inhibitors.
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Affiliation(s)
- Raffaele Bruno
- Division of Infectious and Tropical Diseases, Istituto di Ricovero e Cura a Carattere Scientifico San Mateo Hospital--University of Pavia, Italy
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Mendes-Corrêa MCJ, Barone AA. Hepatitis C in patients co-infected with human immunodeficiency virus. A review and experience of a Brazilian ambulatory. Rev Inst Med Trop Sao Paulo 2005; 47:59-64. [PMID: 15880215 DOI: 10.1590/s0036-46652005000200001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission mechanisms. The prevalence of HCV in the HIV-infected population varies from region to region, throughout the world, depending on different exposure factors to both viruses. Co-infection with HIV accelerates the progression of the disease caused by HCV, appears to worsen the progression of the HIV infection and increases HCV transmission. Therefore, clinical management and treatment of HCV is a priority in medical facilities that receive HIV-infected patients. Clinical management of these patients involves specific diagnostic procedures and appropriately trained medical staff. The indication of treatment should meet specific clinical and laboratory criteria. There are a number of drugs currently available to treat hepatitis C in co-infected patients.
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Pivert A, Payan C, Lunel F. Comparaison des cinétiques de l’ARN et de l’antigène de capside du virus de l’hépatite C dans le suivi thérapeutique des patients co-infectés par le virus de l’hépatite C et le virus de l’immunodéficience humaine, traités par bithérapie interféron–ribavirine, dans le cadre du protocole RIBAVIC. ACTA ACUST UNITED AC 2004; 52:522-8. [PMID: 15531116 DOI: 10.1016/j.patbio.2004.07.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2004] [Accepted: 07/23/2004] [Indexed: 02/06/2023]
Abstract
AIM OF STUDY The RIBAVIC protocol, established by ANRS in 2001 and closed in 2003, compared the efficacy and the tolerance of two bitherapy anti-Hepatitis C Virus for HIV-HCV co-infected patients: IFN-ribavirin and PEG-IFN-ribavirin for 48 weeks. Two hundred patients from protocol were tested for hepatitis C virus core antigen, to study this viral marker kinetics, before and under treatment, in comparison with hepatitis C virus RNA evolution. MATERIAL AND METHODS The available samples for the 204 patients of our study were tested for RNA detection (COBAS AMPLICOR v2.0, Roche Diagnostics) and quantification (VERSANT HCV RNA v3.0, Bayer Diagnostics) and for quantification of core antigen (Ortho trak-C Assay, Ortho Clinical Diagnostics). The viral kinetics were established from samples quantified at D0, W2, W4, W12, W24, W48, W52, W72 (W =week), according to virological response assessed by PCR, six month after the end of treatment (non responders, sustained responders, relapsers et breakthroughs). RESULTS We obtained, for each type of response, similar evolution of both viral markers. Trak-C assay show to be enough sensitive, with similar results whatever genotype of hepatitis C virus. The Pearson's correlation is excellent (R =0.94; P <0.001). The intergenotype correlation is correct too, whatever HCV genotype (1, 2, 3, 4). CONCLUSIONS The HCV core antigen quantification by trak-C assay is a new tool for the follow-up of the treatment of patients with chronic hepatitis C and HIV co-infected.
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Affiliation(s)
- A Pivert
- Laboratoire de bactériologie virologie hygiène hospitalière, CHU de Angers, France.
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Marinho RT, Pinto RM, Santos ML, de Moura MC. Lymphocyte T helper-specific reactivity in sustained responders to interferon and ribavirin with negativation (seroreversion) of anti-hepatitis C virus. Liver Int 2004; 24:413-8. [PMID: 15482336 DOI: 10.1111/j.1478-3231.2004.0947.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Seroreversion, negativation of anti-hepatitis C virus previously positive, is sometimes found in some chronic hepatitis C-sustained responders (SRs) to antiviral therapy. AIMS To determine the probability of seroreversion in SR treatment with Interferon and Ribavirin, and lymphocyte T helper (CD4+) reactivity to HCV antigens. METHODS Thirty SR were followed on average for 54.8 months. Anti-HCV was tested by third generation test. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and cultured to evaluate CD4+ proliferation in response to 2 microg/ml of eight HCV recombinant antigens from core, NS3, NS4, NS5 regions. RESULTS Seroreversion was verified in 23% of patients (7/30), appearing at 47.5+/-24.0 months. The probability of anti-HCV loss in this group was 25% at 56 months after ending therapy. In 57% (4/7), anti-HCV returned to positive. These 7 SR patients with seroreversion also showed weaker CD4+ reactivity in 5% of tests (3/56) than the remaining 23 anti-HCV-positive SRs who showed stronger reactivity in 18% of tests (33/184), P=0.036. CONCLUSIONS One-quarter of the SR showed seroreversion of anti-HCV and weaker CD4+ specific HCV proliferation than those who remained anti-HCV positive. The data suggest that complete viral eradication is a possible and achievable clinical objective.
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Affiliation(s)
- Rui T Marinho
- Liver Unit, Centre of Gastroenterology, Institute for Molecular Medicine, Medical School of Lisbon, Portugal.
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36
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Law WP, Duncombe CJ, Mahanontharit A, Boyd MA, Ruxrungtham K, Lange JMA, Phanuphak P, Cooper DA, Dore GJ. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort. AIDS 2004; 18:1169-77. [PMID: 15166532 DOI: 10.1097/00002030-200405210-00010] [Citation(s) in RCA: 116] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of Thai HIV-infected patients enrolled in eight HIV-NAT randomized controlled trials of antiretroviral therapy (n = 692). Hepatitis B virus (HBV) and hepatitis C virus (HCV) testing was performed on stored serum. RESULTS Mean age was 32.3 years, 52% were male, 11% had CDC category C HIV disease at baseline, and 22% had received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV co-infection was 8.7, 7.2 and 0.4%, respectively. Median HIV RNA reductions (log10 copies/ml) were approximately 1.5 for HIV, HIV-HBV, HIV-HCV subgroups from week 4 up to week 48. Mean increases in CD4 cell count were significantly lower among HIV-HBV and HIV-HCV subgroups at week 4 (HIV, 62 x 10(6) cells/l; HIV-HBV, 29 x 10(6) cells/l; HIV-HCV, 33 x 10(6) cells/l), however, by week 48 CD4 cell increases were similar (HIV, 115 x 10(6) cells/l; HIV-HBV, 113 x 10(6) cells/l; HIV-HCV, 97 x 10(6) cells/l). Cox regression analyses showed that HIV-HBV or HIV-HCV co-infection were not associated with a CD4 cell count increase of 100 x 10(6) cells/l over 48 weeks. Estimated progression to AIDS event or death at week 48 was 3.3% (95% confidence interval, 2.0-5.1%) for HIV, 6.7% (2.5-14.6%) for HIV-HBV, and 8.0% (2.2-20.5%) for HIV-HCV subgroups (P > 0.05). CONCLUSIONS An early delayed CD4 count recovery among HIV/viral hepatitis co-infected patients was not sustained, and was not associated with increased HIV disease progression.
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Affiliation(s)
- W Phillip Law
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Darlinghurst, Sydney, Australia
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Martial J, Morice Y, Abel S, Cabié A, Rat C, Lombard F, Edouard A, Pierre-Louis S, Garsaud P, Béra O, Chout R, Gordien E, Deny P, Césaire R. Hepatitis C virus (HCV) genotypes in the Caribbean island of Martinique: evidence for a large radiation of HCV-2 and for a recent introduction from Europe of HCV-4. J Clin Microbiol 2004; 42:784-91. [PMID: 14766854 PMCID: PMC344442 DOI: 10.1128/jcm.42.2.784-791.2004] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Molecular epidemiological studies of hepatitis C virus (HCV) in the Caribbean may help to specify the origin and spread of HCV infection. Indeed, the Caribbean population is intermixed from European and African origins and geographically close to the American continent. We characterized HCV genotypes in the Caribbean island of Martinique. HCV genotypes were analyzed by sequencing or reverse hybridization in the 5' noncoding region (5'NC) in 250 HCV-monoinfected and 85 HCV-human immunodeficiency virus (HIV)-coinfected patients. In addition, sequencing in the nonstructural 5B (NS5B) gene was required to determine the subtype or to perform phylogenetic analysis in selected samples. Genotypes 1 to 6 were found, respectively, in 84.4, 6.8, 5.2, 2.8, 0.4, and 0.4% of 250 HCV-monoinfected patients and in 71.7, 7.1, 15.3, 5.9, 0, and 0% of 85 HCV-HIV-coinfected patients. HCV-1b was found in 66.4% of the HCV-monoinfected patients and was associated with blood transfusion, whereas HCV-1a was detected in 41.2% of the HCV-HIV-coinfected patients and was associated with intravenous drug use (IVDU). The HCV-3 strains belonged to subtype 3a and were linked to IVDU. Phylogenetic analyses were focused on HCV-2 and HCV-4, which are common in Africa. Two opposite patterns were evidenced. NS5B sequences from 19 HCV-2 isolates were affiliated with many different subtypes described either in Europe or in West Africa, suggesting an ancient radiation. In contrast, seven of the nine HCV-4 NS5B sequences ranged within HCV-4a and HCV-4d clusters spreading in continental France by the IVDU route. Epidemiological data demonstrate the recent introduction of HCV-4a and -4d subtypes into the Caribbean.
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Affiliation(s)
- Jenny Martial
- Laboratoire de Virologie-Immunologie. Service de Maladies Infectieuses et Tropicales, Université Paris 13, Bobigny, France
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38
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Pol S, Lebray P, Vallet-Pichard A. HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. Clin Infect Dis 2004; 38 Suppl 2:S65-72. [PMID: 14986277 DOI: 10.1086/381499] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Liver enzyme elevations are common in human immunodeficiency virus (HIV)-infected patients, and their diagnosis or management may be difficult because of the intricacies of the pathogenic mechanisms involved. These include hepatotoxicity related to the highly active antiretroviral therapy (HAART) regimen, idiosyncratic or immunoallergic mechanisms, and direct cytotoxicity enhanced by an underlying liver disease. Liver enzyme abnormalities may also reflect hepatitis B (HBV) or hepatitis C (HCV) infection, which each have their own risks for chronic immune-mediated liver disease (including hepatitis flare after immune reconstitution) and of direct cytotoxicity. Finally, other factors may affect liver deterioration, including alcohol-related liver disease, nonalcoholic steatohepatitis associated with metabolic syndromes (e.g., hyperlipidemia, diabetes, or being overweight) that are potentially HAART related, and use of medication or illicit drugs (e.g., methamphetamine). A better understanding of these complex interactions, including adjustments of dosages of antiretroviral drugs, will probably help in the management of HIV-infected patients with liver enzyme abnormalities.
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Affiliation(s)
- Stanislas Pol
- Unité d'Hépatologie and INSERM U-370, Hôpital Necker, Paris, France.
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39
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Neau D, Trimoulet P, Winnock M, Rullier A, Le Bail B, Lacoste D, Ragnaud JM, Bioulac-Sage P, Lafon ME, Chêne G, Dupon M. Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for treatment of chronic hepatitis C in human immunodeficiency virus-coinfected patients. Clin Infect Dis 2003; 36:1564-71. [PMID: 12802757 DOI: 10.1086/375067] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2002] [Accepted: 01/16/2003] [Indexed: 01/24/2023] Open
Abstract
An open-label, randomized trial was conducted to compare the efficacy and safety of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN-alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks, followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31 patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22 weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients). Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week 12. Sustained virological response was achieved in 10 patients (15%; 6 in group A and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3 log(10) copies/mL between inclusion and week 4 were associated with virological response. In conclusion, the combination of conventional IFN-alpha-2a and ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.
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Affiliation(s)
- Didier Neau
- Fédération des Maladies Infectieuses, Centre Hospitalo-Universitaire Pellegrin, Bordeaux, France.
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40
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41
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Tedaldi EM, Hullsiek KH, Malvestutto CD, Arduino RC, Fisher EJ, Gaglio PJ, Jenny-Avital ER, McGowan JP, Perez G. Prevalence and characteristics of hepatitis C virus coinfection in a human immunodeficiency virus clinical trials group: the Terry Beirn Community Programs for Clinical Research on AIDS. Clin Infect Dis 2003; 36:1313-7. [PMID: 12746778 DOI: 10.1086/374841] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2002] [Accepted: 01/17/2003] [Indexed: 01/16/2023] Open
Abstract
The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.
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Affiliation(s)
- Ellen M Tedaldi
- Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
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42
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Tamalet C, Colson P. Reciprocal influence of HIV and HCV infections in co-infected patients and the involvement of HAART. Clin Microbiol Infect 2003; 9:159-60. [PMID: 12667247 DOI: 10.1046/j.1469-0691.2003.00540.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The reciprocal influence of HIV-HCV co-infection was established prior to the era of highly active retroviral therapy (HAART) and continues to be a topic of debate, including the question of which infection to treat first.
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43
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Baillargeon J, Wu H, Kelley MJ, Grady J, Linthicum L, Dunn K. Hepatitis C seroprevalence among newly incarcerated inmates in the Texas correctional system. Public Health 2003; 117:43-8. [PMID: 12802904 DOI: 10.1016/s0033-3506(02)00009-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The seroprevalence of hepatitis C (HCV) infection was examined among a sample of incoming inmates in the Texas Department of Criminal Justice (TDCJ) prison system. Rates were compared across demographic factors and three types of prison facilities: substance abuse felony punishment units (SAFPs), state jails and prisons. The study sample consisted of 3712 incoming inmates incarcerated for any duration, dating from 1 November 1998 to 31 May 1999. Among males, inmates entering SAFPs and state jails had comparable HCV infection rates (29.7 and 27.0%, respectively) to those entering prisons (27.3%). Among females, inmates entering prisons had a higher rate of infection (48.6%) than those entering state jails (35.1%) or SAFPs (38.3%). For both genders, blacks exhibited a lower overall infection rate than whites and Hispanics, and HCV seroprevalence increased in a stepwise fashion with age. All subgroups of TDCJ inmates, including those held in alternative correctional facilities, exhibited HCV infection rates that were comparable with previous reports of inmate populations, but dramatically higher than general community samples. Given that most inmates held in alternative facilities will return to the general community in a short period of time, understanding the HCV infection rates in these subgroups holds particular public health relevance.
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Affiliation(s)
- J Baillargeon
- Department of Pediatrics, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7802, USA.
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44
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Cacoub P, Benhamou Y. [Role of interferons in the treatment of hepatitis B and hepatitis C virus infections]. Rev Med Interne 2002; 23 Suppl 4:459s-474s. [PMID: 12481401 DOI: 10.1016/s0248-8663(02)00660-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Since the discovery of hepatitis C (HCV), the efficacy of treatment has significantly progressed using standard mono-therapy: with Interferon alpha (IFN) during six months we obtained approximately 10% sustained response and currently with the association of pegylated IFN and Ribavirin a 55% sustained response was achieved. CURRENT POSITION AND MAJOR POINTS HCV infection continues to present therapeutic problems which have not entirely been solved, mainly related to clinical and biological tolerance, and non-responders. Moreover, the care of patients with extra-hepatic localization, cirrhotic patients, as well as therapeutic problems of co-infected HIV-HCV patients. As regards hepatitis B (HBV) new effective treatments against this virus have appeared, IFN then nucleoside analogs, some of which are available in France (i.e. lamivudine, adefovir, dipovoxil). The main objective of chronic hepatitis B treatment is to obtain the complete inhibition of the HBV virus by Hbe-antigen antibody seroconversion which would therefore significantly increase patient survival. In this article the advantages and disadvantages of the different treatments are assessed. FUTURE PERSPECTIVES Despite the considerable and rapid progress obtained in the therapeutic treatment of infection due to HCV and HBV a number of unknown factors remain, which warrants further trials, in particular to evaluate the efficacy as well as the tolerance of the antiviral agent association.
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Affiliation(s)
- P Cacoub
- Service de médecine interne, hôpital La Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75651 Paris, France.
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45
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George SL, Gebhardt J, Klinzman D, Foster MB, Patrick KD, Schmidt WN, Alden B, Pfaller MA, Stapleton JT. Hepatitis C virus viremia in HIV-infected individuals with negative HCV antibody tests. J Acquir Immune Defic Syndr 2002; 31:154-62. [PMID: 12394793 DOI: 10.1097/00126334-200210010-00005] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Hepatitis C virus (HCV) viremia may occur in persons without detectable HCV antibodies and has been reported in as many as 5.5% of HIV-positive persons. To better characterize serosilent HCV infection, the authors prospectively tested 131 HIV-positive persons and 102 HIV-negative control subjects with diabetes for the presence of HCV antibody (Ab) and HCV RNA. Thirty of 31 HCV Ab-positive (AbP) HIV-positive people tested positive for HCV RNA as did both HCV AbP, HIV-negative control subjects. Similarly, none of the 100 HIV-negative, HCV Ab-negative (AbN) control subjects was HCV RNA positive (p<.001). In contrast, 19 of 100 HIV-positive, HCV AbN persons met stringent criteria for HCV viremia, and 9 of these 19 people were HCV RNA positive when tested by a commercially available HCV RNA detection method. The mean duration of HCV viremia in HCV AbN people was 26.8 months (range, 1-99 months). None of the subjects developed HCV antibody during the study. The HIV-positive, HCV AbP, and RNA-positive group was significantly more likely to have acquired HIV parenterally (p<.001), have higher initial CD4 counts (p=.029), and have higher ALT values than the HCV AbN group (p<.002). In summary, HCV infection appears to occur more frequently among HIV-infected, HCV-seronegative persons than appreciated, especially if HIV acquisition was through sexual as opposed to parenteral risk factors and was associated with a lower initial CD4 count and lower ALT values.
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Affiliation(s)
- Sarah L George
- Department of Internal Medicine, Iowa City Veterans Administration Medical Center, University of Iowa, College of Medicine, 52242, USA
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Rancinan C, Neau D, Savès M, Lawson-Ayayi S, Bonnet F, Mercié P, Dupon M, Couzigou P, Dabis F, Chêne G. Is hepatitis C virus co-infection associated with survival in HIV-infected patients treated by combination antiretroviral therapy? AIDS 2002; 16:1357-62. [PMID: 12131212 DOI: 10.1097/00002030-200207050-00007] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To study whether hepatitis C virus (HCV) co-infection or the severe elevation of transaminases is associated with survival after the initiation of antiretroviral combination therapy. DESIGN Prospective hospital-based cohort (Aquitaine Cohort). METHODS HIV-infected adults started on an antiretroviral combination before 30 June 1999. HCV infection was defined as antibody detection or positive HCV RNA. Severe elevation of transaminases was defined as a value of aspartate or alanine aminotransferase (AST, ALT) above five times the upper limit of normal values. Survival was studied using a Cox model, including at least baseline HCV status and transaminases as a time-dependent covariate. RESULTS Overall, 995 patients were analysed, including 576 HCV-positive individuals (58%). At baseline, HCV-positive patients were younger, more often injecting drug users and women, and had more frequently elevated transaminases. A shorter survival was associated with AIDS stage [hazard ratio (HR) versus non-AIDS 1.67; 95% confidence interval (CI) 1.03; 2.68], lower CD4 cell count (HR for 50 cells/mm3 lower 1.33; CI 1.17; 1.51), lower haemoglobin (HR for 1 g/dl lower 1.20; CI 1.07; 1.35), lower platelet count (HR for 10 000 cells/mm3 lower 1.04; CI 1.01; 1.07), and AST during follow-up (HR for > or = 200 IU/l 2.30; CI 1.32; 4.03). HCV co-infection (HR 1.20; CI 0.75; 1.92) was not statistically associated with survival. CONCLUSION The occurrence of a severe elevation of transaminases was associated with poorer survival, although HCV was not. If liver toxicity may be treatment induced, plasma drug concentrations could guide dosage adjustments of antiretroviral treatments currently prescribed to optimize their use.
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48
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Trimoulet P, Neau D, Le Bail B, Rullier A, Winnock M, Galperine T, Legrand E, Schvoerer E, Dupon M, Ragnaud JM, Bioulac-Sage P, Chêne G, Fleury H, Lafon ME. Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection. J Med Virol 2002; 67:143-51. [PMID: 11992575 DOI: 10.1002/jmv.2203] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.
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Affiliation(s)
- P Trimoulet
- Laboratoire de Virologie, Centre Hospitalo-Universitaire, Bordeaux, France.
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Palmon R, Koo BCA, Shoultz DA, Dieterich DT. Lack of hepatotoxicity associated with nonnucleoside reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2002; 29:340-5. [PMID: 11917237 DOI: 10.1097/00126334-200204010-00003] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.
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Affiliation(s)
- Ron Palmon
- Department of Medicine, New York University School of Medicine, New York City, New York, USA
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Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 2002; 35:182-9. [PMID: 11786975 DOI: 10.1053/jhep.2002.30319] [Citation(s) in RCA: 345] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Hepatologists are frequently asked to evaluate human immunodeficiency virus (HIV)-infected patients with abnormal liver enzymes and to assess the causal role of medications, such as antiretroviral drugs. Recently, the use of HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine (NVP) and efavirenz (EFV), has been associated with severe hepatic injury. We prospectively studied the incidence of severe hepatotoxicity (grade 3 or 4 change in alanine or aspartate transaminase levels) among 568 patients receiving NNRTI-containing antiretroviral therapy, including 312 and 256 patients prescribed EFV and NVP, respectively. Hepatitis C virus (HCV) and hepatitis B virus (HBV) were detected in 43% and 7.7% of patients, respectively. Severe hepatotoxicity was observed in 15.6% of patients prescribed NVP and 8.0% of those prescribed EFV, but only 32% of NVP and 50% of EFV-associated episodes were detected during the first 12-weeks of therapy. The risk was significantly greater among persons with chronic viral hepatitis (69% of cases) and those prescribed concurrent protease inhibitors (PIs) (82% of cases). Nonetheless, 84% of patients with chronic HCV or HBV did not experience severe hepatotoxicity. Severe hepatotoxicity occurs throughout the course of NNRTI therapy and is more common among patients prescribed nevirapine, those coinfected with HCV or HBV, and those coadministered protease inhibitors.
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Affiliation(s)
- Mark S Sulkowski
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
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