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Ma J, Nance RM, Cachay E, Ruderman SA, Kitahata M, Falade-Nwulia O, Chander G, Drumright LN, Hurt CB, Yendewa GA, Pettit A, Moore RD, Fredericksen RJ, Lloyd A, Bamford L, Napravnik S, Fleming J, Christopoulos K, Burkholder G, Keruly J, Delaney JAC, Crane H, Kim HN. Prevalence and Correlates of Hepatitis C Viremia Among People With Human Immunodeficiency Virus in the Direct-Acting Antiviral Era. Open Forum Infect Dis 2025; 12:ofaf030. [PMID: 39896988 PMCID: PMC11786118 DOI: 10.1093/ofid/ofaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/16/2025] [Indexed: 02/04/2025] Open
Abstract
Background National US data on the burden and risks for hepatitis C virus (HCV) infection in people with human immunodeficiency virus (HIV) during the direct-acting antiviral (DAA) era are limited. These data are important to understand current progress and guide future efforts toward HCV microelimination. Methods We evaluated (1) HCV prevalence (2011-2013, 2014-2017, 2018-2022) using a serial cross-sectional design and (2) correlates for HCV viremia (2018-2022) in adult people with HIV (PWH) within the Centers for AIDS Research Network of Integrated Clinic Systems (CNICS) cohort using multivariable adjusted relative risk regression. The most recent data from each time period were used for calculations and models. Results In the CNICS cohort, HCV viremia prevalence was 8.7% in 2011-2013, 10.5% in 2014-2017, and 4.8% in 2018-2022. Disparities in prevalence across demographic groups defined by age, gender, and race/ethnicity were smaller in 2018-2022 than earlier time periods. In relative risk regression, female gender, detectable HIV RNA, higher proportion of missed visits (last 18 months), higher FIB-4 score, higher depressive symptom severity, and current use of methamphetamine and illicit opioids were associated with HCV viremia in 2018-2022. Conclusions The prevalence of HCV viremia during the DAA era in this US-based national cohort of PWH improved over time and across demographic subgroups but remains higher than those without HIV. Our findings highlight the continued importance of prioritizing HCV care in all PWH, especially in certain key, less-reached groups. Proactive, comprehensive efforts to care engagement, substance use, mental health, and other social determinants will be crucial to improve reach, prevention, and treatment to achieve HCV elimination goals.
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Affiliation(s)
- Jimmy Ma
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Robin M Nance
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Edward Cachay
- Department of Medicine, University of California, San Diego, San Diego, California, USA
| | | | - Mari Kitahata
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Geetanjali Chander
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lydia N Drumright
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Christopher B Hurt
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - George A Yendewa
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - April Pettit
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Richard D Moore
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Rob J Fredericksen
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Audrey Lloyd
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Laura Bamford
- Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Sonia Napravnik
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Julia Fleming
- The Fenway Institute, Fenway Health, Boston, Massachusetts, USA
| | - Katerina Christopoulos
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Greer Burkholder
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jeanne Keruly
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joseph A C Delaney
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Heidi Crane
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - H Nina Kim
- Department of Medicine, University of Washington, Seattle, Washington, USA
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Lodi S, Klein M, Rauch A, Epstein R, Wittkop L, Logan R, Rentsch CT, Justice AC, Touloumi G, Berenguer J, Jarrin I, Egger M, Puoti M, D'Arminio Monforte A, Gill J, Salmon Ceron D, van Sighem A, Linas B, van der Valk M, Hernán MA, HepCAUSAL Collaboration. Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co-infection. J Int AIDS Soc 2022; 25:e26048. [PMID: 36562643 PMCID: PMC9784654 DOI: 10.1002/jia2.26048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 11/18/2022] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. METHODS We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. RESULTS AND DISCUSSION A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. CONCLUSIONS Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.
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Affiliation(s)
- Sara Lodi
- Department of BiostatisticsBoston University School of Public HealthBostonMassachusettsUSA
- CAUSALab, Harvard T.H. Chan School of Public HealthBostonMassachusettsUSA
| | - Marina Klein
- Division of Infectious Diseases and Chronic Viral Illness ServiceDepartment of MedicineMcGill UniversityMontrealQuebecCanada
- Department of EpidemiologyBiostatistics and Occupational HealthMcGill UniversityMontrealQuebecCanada
| | - Andri Rauch
- Department of Infectious DiseasesInselspitalBern University HospitalUniversity of BernBernSwitzerland
| | - Rachel Epstein
- Department of PediatricsSection of Infectious DiseasesBoston University School of MedicineBostonMassachusettsUSA
- Department of MedicineSection of Infectious DiseasesBoston University School of MedicineBostonMassachusettsUSA
| | - Linda Wittkop
- ISPED, INSERMBordeaux Population Health Research CenterUniversity of BordeauxBordeauxFrance
- CHU de BordeauxPôle de Santé PubliqueBordeauxFrance
| | - Roger Logan
- CAUSALab, Harvard T.H. Chan School of Public HealthBostonMassachusettsUSA
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMassachusettsUSA
| | - Christopher T. Rentsch
- Department of Internal MedicineYale School of MedicineNew HavenConnecticutUSA
- VA Connecticut Healthcare SystemUS Department of Veterans AffairsNew HavenConnecticutUSA
- Faculty of Epidemiology and Population HealthLondon School of Hygiene & Tropical MedicineLondonUK
| | - Amy C. Justice
- Department of Internal MedicineYale School of MedicineNew HavenConnecticutUSA
- VA Connecticut Healthcare SystemUS Department of Veterans AffairsNew HavenConnecticutUSA
- Department of Health PolicyYale School of Public HealthNew HavenConnecticutUSA
| | - Giota Touloumi
- Department of HygieneEpidemiology & Medical StatisticsMedical SchoolNational & Kapodistrian University of AthensAthensGreece
| | - Juan Berenguer
- Hospital General Universitario Gregorio MarañónMadridSpain
| | - Inma Jarrin
- Centro Nacional de EpidemiologiaInstitute of Health Carlos IIIMadridSpain
| | - Matthias Egger
- Institute of Social and Preventive MedicineUniversity of BernBernSwitzerland
| | - Massimo Puoti
- School of Medicine and SurgeryUniversity of Milan Bicocca – ASST GOM Niguarda MilanMilanoItaly
| | | | - John Gill
- Southern Alberta ClinicCalgaryAlbertaCanada
- Department of MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Dominique Salmon Ceron
- Department of Infectious Diseases and ImmunologyHotel Dieu HospitalParis Public Hospitals (APHP)ParisFrance
- School of MedicineUniversity of ParisParisFrance
| | | | - Benjamin Linas
- Boston Medical Center and EpidemiologyBostonMassachusettsUSA
- Boston University Schools of Medicine and EpidemiologyBostonMassachusettsUSA
| | - Marc van der Valk
- Department of Internal MedicineAmsterdam Infection and Immunity Institute and Amsterdam Public Health Research InstituteAmsterdamThe Netherlands
- University of AmsterdamAmsterdamThe Netherlands
| | - Miguel A. Hernán
- CAUSALab, Harvard T.H. Chan School of Public HealthBostonMassachusettsUSA
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMassachusettsUSA
- Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonMassachusettsUSA
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Mousavi SM, Hashemi SA, Kalashgrani MY, Gholami A, Omidifar N, Babapoor A, Vijayakameswara Rao N, Chiang WH. Recent Advances in Plasma-Engineered Polymers for Biomarker-Based Viral Detection and Highly Multiplexed Analysis. BIOSENSORS 2022; 12:286. [PMID: 35624587 PMCID: PMC9138656 DOI: 10.3390/bios12050286] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/22/2022] [Accepted: 04/27/2022] [Indexed: 05/07/2023]
Abstract
Infectious diseases remain a pervasive threat to global and public health, especially in many countries and rural urban areas. The main causes of such severe diseases are the lack of appropriate analytical methods and subsequent treatment strategies due to limited access to centralized and equipped medical centers for detection. Rapid and accurate diagnosis in biomedicine and healthcare is essential for the effective treatment of pathogenic viruses as well as early detection. Plasma-engineered polymers are used worldwide for viral infections in conjunction with molecular detection of biomarkers. Plasma-engineered polymers for biomarker-based viral detection are generally inexpensive and offer great potential. For biomarker-based virus detection, plasma-based polymers appear to be potential biological probes and have been used directly with physiological components to perform highly multiplexed analyses simultaneously. The simultaneous measurement of multiple clinical parameters from the same sample volume is possible using highly multiplexed analysis to detect human viral infections, thereby reducing the time and cost required to collect each data point. This article reviews recent studies on the efficacy of plasma-engineered polymers as a detection method against human pandemic viruses. In this review study, we examine polymer biomarkers, plasma-engineered polymers, highly multiplexed analyses for viral infections, and recent applications of polymer-based biomarkers for virus detection. Finally, we provide an outlook on recent advances in the field of plasma-engineered polymers for biomarker-based virus detection and highly multiplexed analysis.
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Affiliation(s)
- Seyyed Mojtaba Mousavi
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
| | - Seyyed Alireza Hashemi
- Nanomaterials and Polymer Nanocomposites Laboratory, School of Engineering, University of British Columbia, Kelowna, BC V1V 1V7, Canada;
| | - Masoomeh Yari Kalashgrani
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran; (M.Y.K.); (A.G.)
| | - Ahmad Gholami
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran; (M.Y.K.); (A.G.)
| | - Navid Omidifar
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran;
| | - Aziz Babapoor
- Department of Chemical Engineering, University of Mohaghegh Ardabil, Ardabil 56199-11367, Iran;
| | - Neralla Vijayakameswara Rao
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
| | - Wei-Hung Chiang
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
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Suda G, Sakamoto N. Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems. J Gastroenterol Hepatol 2021; 36:1152-1158. [PMID: 32667068 DOI: 10.1111/jgh.15189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Sugawara S, El-Diwany R, Cohen LK, Rousseau KE, Williams CYK, Veenhuis RT, Mehta SH, Blankson JN, Thomas DL, Cox AL, Balagopal A. People with HIV-1 demonstrate type 1 interferon refractoriness associated with upregulated USP18. J Virol 2021; 95:JVI.01777-20. [PMID: 33658340 PMCID: PMC8139647 DOI: 10.1128/jvi.01777-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 02/19/2021] [Indexed: 01/04/2023] Open
Abstract
HIV-1 infection persists in humans despite expression of antiviral type 1 interferons (IFN). Even exogenous administration of IFNα only marginally reduces HIV-1 abundance, raising the hypothesis that people living with HIV-1 (PLWH) are refractory to type 1 IFN. We demonstrated type 1 IFN refractoriness in CD4+ and CD8+ T cells isolated from HIV-1 infected persons by detecting diminished STAT1 phosphorylation (pSTAT1) and interferon-stimulated gene (ISG) induction upon type 1 IFN stimulation compared to healthy controls. Importantly, HIV-1 infected people who were virologically suppressed with antiretrovirals also showed type 1 IFN refractoriness. We found that USP18 levels were elevated in people with refractory pSTAT1 and ISG induction and confirmed this finding ex vivo in CD4+ T cells from another cohort of HIV-HCV coinfected persons who received exogenous pegylated interferon-α2b in a clinical trial. We used a cell culture model to recapitulate type 1 IFN refractoriness in uninfected CD4+ T cells that were conditioned with media from HIV-1 inoculated PBMCs, inhibiting de novo infection with antiretroviral agents. In this model, RNA interference against USP18 partly restored type 1 IFN responses in CD4+ T cells. We found evidence of type 1 IFN refractoriness in PLWH irrespective of virologic suppression that was associated with upregulated USP18, a process that might be therapeutically targeted to improve endogenous control of infection.ImportancePeople living with HIV-1 (PLWH) have elevated constitutive expression of type 1 interferons (IFN). However, it is unclear whether this impacts downstream innate immune responses. We identified refractory responses to type 1 IFN stimulation in T cells from PLWH, independent of antiretroviral treatment. Type 1 IFN refractoriness was linked to elevated USP18 levels in the same cells. Moreover, we found that USP18 levels predicted the anti-HIV-1 effect of type 1 IFN-based therapy on PLWH. In vitro, we demonstrated that refractory type 1 IFN responses were transferrable to HIV-1 uninfected target CD4+ T cells, and this phenomenon was mediated by type 1 IFN from HIV-1 infected cells. Type 1 IFN responses were partially restored by USP18 knockdown. Our findings illuminate a new mechanism by which HIV-1 contributes to innate immune dysfunction in PLWH, through the continuous production of type 1 IFN that induces a refractory state of responsiveness.
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Affiliation(s)
- Sho Sugawara
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ramy El-Diwany
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Laura K Cohen
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kimberly E Rousseau
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Rebecca T Veenhuis
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Shruti H Mehta
- Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA
| | - Joel N Blankson
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David L Thomas
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrea L Cox
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ashwin Balagopal
- Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Sun J, Althoff KN, Jing Y, Horberg MA, Buchacz K, Gill MJ, Justice AC, Rabkin CS, Goedert JJ, Sigel K, Cachay E, Park L, Lim JK, Kim HN, Lo Re V, Moore R, Sterling T, Peters MG, Achenbach CJ, Silverberg M, Thorne JE, Mayor AM, Crane HM, Kitahata MM, Klein M, Kirk GD. Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Netw Open 2021; 4:e2037512. [PMID: 33595662 PMCID: PMC7890526 DOI: 10.1001/jamanetworkopen.2020.37512] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/28/2020] [Indexed: 12/29/2022] Open
Abstract
IMPORTANCE People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. OBJECTIVE To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. EXPOSURES HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. MAIN OUTCOMES AND MEASURES HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. RESULTS Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. CONCLUSIONS AND RELEVANCE HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.
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Affiliation(s)
- Jing Sun
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Keri N. Althoff
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Yuezhou Jing
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael A. Horberg
- Kaiser Permanente Mid-Atlantic States, Mid-Atlantic Permanente Research Institute, Rockville, Maryland
| | - Kate Buchacz
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - M. John Gill
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Amy C. Justice
- Department of Medicine, Yale University, West Haven, Connecticut
| | | | | | - Keith Sigel
- Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Edward Cachay
- Department of Medicine, University of California, San Diego, San Diego
| | - Lesley Park
- Center for Population Health Sciences, Stanford University School of Medicine, Stanford, California
| | - Joseph K. Lim
- Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - H. Nina Kim
- Department of Medicine, University of Washington, Seattle
| | - Vincent Lo Re
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
- Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
- Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia
| | - Richard Moore
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Timothy Sterling
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Marion G. Peters
- Department of Medicine, University of California, San Francisco, San Francisco
| | - Chad J. Achenbach
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | | | - Angel M. Mayor
- Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico
| | - Heidi M. Crane
- Department of Medicine, University of Washington School of Medicine, Seattle
| | - Mari M. Kitahata
- Department of Medicine, University of Washington School of Medicine, Seattle
| | - Marina Klein
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
| | - Gregory D. Kirk
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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Millman AJ, Luo Q, Nelson NP, Vellozzi C, Weiser J. Missed opportunities for prevention and treatment of hepatitis C among persons with HIV/HCV coinfection. AIDS Care 2020; 32:921-929. [PMID: 31547683 PMCID: PMC7085966 DOI: 10.1080/09540121.2019.1668533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 09/11/2019] [Indexed: 12/17/2022]
Abstract
Hepatitis C (HCV) and HIV have common modes of transmission but information about HCV transmission risk, prevention, and treatment among persons with coinfection is lacking. The Medical Monitoring Project produces nationally representative estimates describing adults with diagnosed HIV in the United States. Using medical record data recorded during 6/2013-5/2017, we identified persons with detectable HCV RNA documented during the past 24 months. Among persons with coinfection, we described HCV transmission risk factors and receipt of HCV prevention services during the past 12 months and prescription of HCV treatment during the past 24 months. Overall, 4.9% had documented active HCV coinfection, among whom 30.2% were men who have sex with men (MSM), 6.7% reported injection drug use, and 62.1% were prescribed HCV treatment. Among MSM, 45.5% reported condomless anal sex and 42.3% received free condoms. Among persons who used drugs, 30.8% received drug or alcohol counseling, and among persons who injected drugs, 79.2% received sterile syringes. Among persons with HIV/HCV coinfection, recent drug injection was uncommon and most received sterile syringes. However, 1 in 3 were MSM, of whom half reported recent HCV sexual transmission risk behaviors. More than one-third of those with coinfection were not prescribed curative HCV treatment.
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Affiliation(s)
- Alexander J Millman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - Noele P Nelson
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Claudia Vellozzi
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - John Weiser
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Hall T, Jenkins CA, Hulgan T, Furukawa S, Turner M, Pratap S, Sterling TR, Tabatabai M, Berthaud V. Hepatitis C Coinfection and Mortality in People Living with HIV in Middle Tennessee. AIDS Res Hum Retroviruses 2020; 36:193-199. [PMID: 31789047 PMCID: PMC7071089 DOI: 10.1089/aid.2019.0113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
HIV and hepatitis C virus (HCV) coinfection is associated with poor health outcomes. This study was designed to assess risk factors for and mortality with coinfection before direct-acting antiviral treatment availability in a state with an evolving opioid epidemic. HCV infection was determined from review of the medical record at two clinics serving the majority of people living with HIV (PLWH) in care in Middle Tennessee from 2004 to 2013. Association of potential risk factors with HCV-positivity was assessed using logistic regression. Association of HCV-positivity with mortality was assessed with a Cox proportional hazards model, adjusting for selected covariates. A total of 3,501 patients were included: 24% female; 51% men who have sex with men; 47% white; 44% African American/black; median age of 38 at their first visit; median most recent CD4 count 502 cells/μL (301-716); and HIV viral load 47 copies/mL (39-605); followed for a median of 3.0 (1-5) years. Prevalence of HCV was 13%. Those with a history of injection drug use (IDU) demonstrated the highest odds of HCV-positivity [odds ratio 12.94; 95% confidence interval (CI) 9.39-17.83]. There were 305 deaths; median age at death was 47 years (40-53). HCV coinfection was associated with greater mortality (hazard ratio 1.61; 95% CI 1.20-2.17; p < .001). Among PLWH, HCV coinfection was associated with IDU and an independent predictor of mortality. These results affirm the importance of HCV coinfection and inform interventions targeting the continuum of HCV care, uptake of HCV treatment, and the impact of drug use in this population.
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Affiliation(s)
- Toni Hall
- Department of Medicine, Meharry Medical College, Nashville, Tennessee
| | - Cathy A Jenkins
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Todd Hulgan
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sally Furukawa
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Megan Turner
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Siddharth Pratap
- Department of Bioinformatics, Meharry Medical College, Nashville, Tennessee
| | - Timothy R Sterling
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Mohammad Tabatabai
- Department of Biostatistics, Meharry Medical College, Nashville, Tennessee
| | - Vladimir Berthaud
- Department of Medicine, Meharry Medical College, Nashville, Tennessee
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Real-world efficacy of direct acting antiviral therapies in patients with HIV/HCV. PLoS One 2020; 15:e0228847. [PMID: 32053682 PMCID: PMC7018045 DOI: 10.1371/journal.pone.0228847] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 01/24/2020] [Indexed: 12/12/2022] Open
Abstract
The advent of direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment, with most recent trials demonstrating high efficacy rates (>90%) across all genotypes and special populations, including patients with HIV/HCV coinfection. The efficacy rates of HCV treatment are nearly identical between patients with HCV monofection and patients with HIV/HCV coinfection; however, there are limited studies to compare real-world efficacy with efficacy observed in clinical trials. Using a database from HIV clinics across the United States (US), we identified 432 patients with HIV/HCV coinfection who completed DAA therapy from January 1, 2014 to March 31, 2017 and were assessed for efficacy. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion; furthermore, factors associated with achieving SVR12 were identified. In this analysis, we found DAA therapies to be effective, with 94% of the patients achieving SVR12 and 6% experiencing virologic failure. Baseline variables, including older age, HCV viral load <800K IU/ML, FIB-4 score <1.45, absence of depression, diabetes, substance abuse, and use of DAA regimens without ribavirin were significant predictors of achieving SVR12. Patients with fewer comorbidities, better liver health, and lower HCV viral loads at baseline were more likely to achieve treatment success. Our results were consistent with other real-world studies, supporting the use of HCV therapy in HIV/HCV coinfected patients.
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10
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Oikonomou KG, Tsai E, Sarpel D, Dieterich DT. Liver Disease in Human Immunodeficiency Virus Infection. Clin Liver Dis 2019; 23:309-329. [PMID: 30947879 DOI: 10.1016/j.cld.2018.12.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.
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Affiliation(s)
- Katerina G Oikonomou
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA.
| | - Eugenia Tsai
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Dost Sarpel
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Douglas T Dieterich
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
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11
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Kim HN, Nance RM, Williams-Nguyen JS, Chris Delaney JA, Crane HM, Cachay ER, Martin J, Mathews WC, Chander G, Franco R, Hurt CB, Geng EH, Rodriguez B, Moore RD, Saag MS, Kitahata MM. Effectiveness of Direct-Acting Antiviral Therapy in Patients With Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in Routine Clinical Care: A Multicenter Study. Open Forum Infect Dis 2019; 6:ofz100. [PMID: 30949539 PMCID: PMC6441587 DOI: 10.1093/ofid/ofz100] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Accepted: 02/25/2019] [Indexed: 02/06/2023] Open
Abstract
Background Direct-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions. Methods The primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values. Results Among 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%-97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%-93.6%). Similar results were seen in multiply imputed data sets. Conclusions Our study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.
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Affiliation(s)
- H Nina Kim
- Department of Medicine, University of Washington, Seattle
| | - Robin M Nance
- Department of Medicine, University of Washington, Seattle
| | | | | | - Heidi M Crane
- Department of Medicine, University of Washington, Seattle
| | | | - Jeffrey Martin
- Department of Medicine, University of California, San Francisco
| | | | | | - Ricardo Franco
- Department of Medicine, University of Alabama, Birmingham
| | - Christopher B Hurt
- Institute for Global Health & Infectious Diseases, University of North Carolina, Chapel Hill
| | - Elvin H Geng
- Department of Medicine, University of California, San Francisco
| | | | - Richard D Moore
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Michael S Saag
- Department of Medicine, University of Alabama, Birmingham
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12
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Sho T, Suda G, Kimura M, Shimazaki T, Maehara O, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Umemura M, Izumi T, Kawagishi N, Baba M, Nakai M, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N. Glecaprevir and Pibrentasvir for Japanese Patients with Human Immunodeficiency Virus and Genotype 3 Hepatitis C Virus Coinfection: A Report of Three Cases. Intern Med 2019; 58:797-802. [PMID: 30449808 PMCID: PMC6465017 DOI: 10.2169/internalmedicine.1856-18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with human immunodeficiency virus (HIV) and/or genotype 3 hepatitis C virus (HCV) infection is yet to be clarified. This is because no or only a few patients have been included in Japanese phase 3 trials. We herein report for the first time the successful treatment of glecaprevir and pibrentasvir in three Japanese patients with HIV and genotype 3 HCV coinfection as well as hemophilia. Glecaprevir and pibrentasvir treatment is safe and effective for Japanese patients with genotype 3 HCV and HIV coinfection.
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Affiliation(s)
- Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Tomoe Shimazaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Osamu Maehara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Machiko Umemura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Takaaki Izumi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Masaru Baba
- Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Japan
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13
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Suda G, Ogawa K, Morikawa K, Sakamoto N. Treatment of hepatitis C in special populations. J Gastroenterol 2018; 53:591-605. [PMID: 29299684 PMCID: PMC5910474 DOI: 10.1007/s00535-017-1427-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 12/19/2017] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
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14
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Spartalis E, Damaskos C, Athanasiou A, Dimitroulis D. The impact of hepatitis C virus and human immunodeficiency virus coinfection on survival in patients with hepatocellular carcinoma. Ann Gastroenterol 2017; 30:471. [PMID: 28655991 PMCID: PMC5480007 DOI: 10.20524/aog.2017.0149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 03/29/2017] [Indexed: 11/11/2022] Open
Affiliation(s)
| | - Christos Damaskos
- Second Department of Propedeutic Surgery (Christos Damaskos, Dimitrios Dimitroulis), University of Athens Medical School, Athens, Greece
| | - Antonios Athanasiou
- Department of Surgery, Mercy University Hospital, Cork, Ireland (Antonios Athanasiou)
| | - Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery (Christos Damaskos, Dimitrios Dimitroulis), University of Athens Medical School, Athens, Greece
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15
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Abstract
OBJECTIVE To assess if the reduction in HIV-1 RNA in CD4 T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). DESIGN Clinical trial (NCT01285050). METHODS Next-generation sequencing was used to study total RNA from activated CD4 T cells (CD38 and human leukocyte antigen - antigen D related (HLA-DR) expressing) collected from 19 treatment-naïve HIV-1/hepatitis C virus-infected patients before and early after ART initiation (≥12 weeks after plasma HIV-1 RNA <50 copies/ml). To validate comparisons, pre and post-ART measures were adjusted for input RNA and overall read number. RESULTS As expected, ART use was associated with a median [interquartile range (IQR)] 4.3% (2.2-8.3) reduction in the proportion of activated CD4 T cells (P = 0.0008). Whereas in those activated CD4 T cells no consistent differences in overall gene expression were detected, interferon-stimulated gene expression declined (P < 2 × 10). Pre-ART, sorted activated CD4 T cells contained a median (IQR) of 959 (252-1614) HIV-1 reads/10 reads compared with 72 (55-152) HIV-1 reads/10 reads after at least 12 weeks of suppressive ART (P = 8 × 10). The decrease in HIV-1 reads in activated CD4 T cells was associated with the change in plasma HIV-1 RNA levels (r = 0.77, P = 2 × 10) and the change in the proportion of activated CD4 T cells (r = 0.70, P = 0.0016). CONCLUSION Months of ART led to a marked decrease in cell-associated HIV-1 RNA and interferon-stimulated genes expression in activated CD4 T cells that were strongly associated with the reduction in the proportion of activated CD4 T cells.
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16
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Wang K, Fan D, Liu Y, Dong S. Cascaded multiple amplification strategy for ultrasensitive detection of HIV/HCV virus DNA. Biosens Bioelectron 2016; 87:116-121. [PMID: 27526400 DOI: 10.1016/j.bios.2016.08.017] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 07/31/2016] [Accepted: 08/05/2016] [Indexed: 12/31/2022]
Abstract
Ultrasensitive detection of HIV and HCV virus DNA is of great importance for early accurate diagnostics and therapy of HIV virus-infected patients. Herein, to our best knowledge, it is the first to use DNA cascaded multiple amplification strategy for ultrasensitive detection of HIV virus DNA with G-quadruplex-specific fluorescent or colorimetric probes as signal carriers. The developed strategy also exhibited universal applicability for HCV virus DNA detection. After reaction for about 4h, high sensitivity and specificity can be achieved at both fluorescent and colorimetric strategies (limit of detection (LOD) of 10 fM and 0.5pM were reached for fluorescent and colorimetric detection, respectively). And the single-based mismatched DNA even can be distinguished by naked eyes. It is believed that the cascaded multiple amplification strategy presents a huge advance in sensing platform and potential application in future clinical diagnosis.
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Affiliation(s)
- Kun Wang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China; Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, PR China
| | - Daoqing Fan
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China
| | - Yaqing Liu
- Key Laboratory of Food Nutrition and Safety (Ministry of Education), Tianjin University of Science and Technology, Tianjin 300457, PR China.
| | - Shaojun Dong
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
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17
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Hull M, Shafran S, Wong A, Tseng A, Giguère P, Barrett L, Haider S, Conway B, Klein M, Cooper C. CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2016; 2016:4385643. [PMID: 27471521 PMCID: PMC4947683 DOI: 10.1155/2016/4385643] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 12/15/2015] [Indexed: 12/13/2022]
Abstract
Background. Hepatitis C virus (HCV) coinfection occurs in 20-30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
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Affiliation(s)
- Mark Hull
- British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
| | | | - Alex Wong
- Regina Qu'Appelle Health Region, Regina, SK, Canada S4P 1E2
| | - Alice Tseng
- Toronto General Hospital, Toronto, ON, Canada M5G 2C4
| | | | - Lisa Barrett
- Dalhousie University, Halifax, NS, Canada B3H 4R2
| | | | - Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, BC, Canada V6Z 2C7
| | | | - Curtis Cooper
- The Ottawa Hospital, General Campus, G12, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6
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18
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Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat 2016; 23:545-59. [PMID: 27028545 DOI: 10.1111/jvh.12519] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 01/14/2016] [Indexed: 12/15/2022]
Abstract
To evaluate the extent of heterogeneity in global estimates of chronic hepatitis B (HBV) and C (HCV) cited in the published literature, we undertook a systematic review of the published literature. We identified articles from 2010 to 2014 that had cited global estimates for at least one of ten indicators [prevalence and numbers infected with HBV, HCV, HIV-HBV or HIV-HCV co-infection, and mortality (number of deaths annually) for HBV and HCV]. Overall, 488 articles were retrieved: 239 articles cited a HBV-related global estimate [prevalence (n = 12), number infected (n = 193) and number of annual deaths (n = 82)]; 280 articles had HCV-related global estimates [prevalence (n = 86), number infected (n = 203) and number of annual deaths (n = 31)]; 31 had estimates on both HBV and HCV; 54 had HIV-HBV co-infection estimates [prevalence (n = 42) and number co-infected (n = 12)]; and 68 had estimates for HIV-HCV co-infection [prevalence (n = 40) and number co-infected (n = 28)]. There was considerable heterogeneity in the estimates cited and also a lack of consistency in the terminology used. Although 40% of 488 articles cited WHO as the source of the estimate, many of these were from outdated or secondary sources. Our findings highlight the importance of clear and consistent communication from WHO and other global health agencies on current consensus estimates of hepatitis B and C burden and prevalence, the need for standardisation in their citation, and for regular updates.
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Affiliation(s)
| | - P J Easterbrook
- Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland
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19
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Kohli P, Ganz P, Ma Y, Scherzer R, Hur S, Weigel B, Grunfeld C, Deeks S, Wasserman S, Scott R, Hsue PY. HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox". J Am Heart Assoc 2016; 5:JAHA.115.002683. [PMID: 27130349 PMCID: PMC4889164 DOI: 10.1161/jaha.115.002683] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Background Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low‐density lipoprotein cholesterol (LDL‐C) and improve outcomes in the general population. HIV‐infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy. Methods and Results We studied 567 participants from a clinic‐based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL‐C level was 100 mg/dL (IQR 77–124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL‐C, and high‐density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV‐coinfected patients versus controls (95% CI 9–34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3–20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8–33%, P=0.001). Interleukin‐6 levels increased in a stepwise fashion from controls (lowest) to HIV‐infected to HIV/HCV‐coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018). Conclusions Despite having lower LDL‐C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin‐6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.
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Affiliation(s)
- Payal Kohli
- Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
| | - Peter Ganz
- Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
| | - Yifei Ma
- Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA
| | - Rebecca Scherzer
- Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA
| | - Sophia Hur
- Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
| | - Bernard Weigel
- Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
| | - Carl Grunfeld
- Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA
| | - Steven Deeks
- The Positive Health Program, San Francisco General Hospital, San Francisco, CA
| | | | | | - Priscilla Y Hsue
- Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
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20
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Frimpong JA, D'Aunno T, Perlman DC, Strauss SM, Mallow A, Hernandez D, Schackman BR, Feaster DJ, Metsch LR. On-site bundled rapid HIV/HCV testing in substance use disorder treatment programs: study protocol for a hybrid design randomized controlled trial. Trials 2016; 17:117. [PMID: 26936623 PMCID: PMC4776446 DOI: 10.1186/s13063-016-1225-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 02/10/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND More than 1.2 million people in the United States are living with human immunodeficiency virus (HIV), and 3.2 million are living with hepatitis C virus (HCV). An estimated 25 % of persons living with HIV also have HCV. It is therefore of great public health importance to ensure the prompt diagnosis of both HIV and HCV in populations that have the highest prevalence of both infections, including individuals with substance use disorders (SUD). METHODS/DESIGN In this theory-driven, efficacy-effectiveness-implementation hybrid study, we will develop and test an on-site bundled rapid HIV/HCV testing intervention for SUD treatment programs. Its aim is to increase the receipt of HIV and HCV test results among SUD treatment patients. Using a rigorous process involving patients, providers, and program managers, we will incorporate rapid HCV testing into evidence-based HIV testing and linkage to care interventions. We will then test, in a randomized controlled trial, the extent to which this bundled rapid HIV/HCV testing approach increases receipt of HIV and HCV test results. Lastly, we will conduct formative research to understand the barriers to, and facilitators of, the adoption, implementation, and sustainability of the bundled rapid testing strategy in SUD treatment programs. DISCUSSION Novel approaches that effectively integrate on-site rapid HIV and rapid HCV testing are needed to address both the HIV and HCV epidemics. If feasible and efficacious, bundled rapid HIV/HCV testing may offer a scalable, potentially cost-effective approach to testing high-risk populations, such as patients of SUD treatment programs. It may ultimately lead to improved linkage to care and progress through the HIV and HCV care and treatment cascades. TRIAL REGISTRATION ClinicalTrials.gov: NCT02355080 . (30 January 2015).
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Affiliation(s)
- Jemima A Frimpong
- Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York, USA.
| | - Thomas D'Aunno
- Robert F. Wagner Graduate School of Public Service, New York University, New York, USA.
| | - David C Perlman
- Mount Sinai Beth Israel; Ichan School of Medicine at Mount Sinai, New York, USA.
| | | | - Alissa Mallow
- Montefiore Health System, New York, USA, New York, USA.
| | - Diana Hernandez
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, USA.
| | - Bruce R Schackman
- Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA.
| | - Daniel J Feaster
- Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, USA.
| | - Lisa R Metsch
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, USA.
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Swallow E, Song J, Yuan Y, Kalsekar A, Kelley C, Peeples M, Mu F, Ackerman P, Signorovitch J. Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison. Clin Ther 2016; 38:404-12. [PMID: 26839044 DOI: 10.1016/j.clinthera.2015.12.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 12/22/2015] [Accepted: 12/31/2015] [Indexed: 11/28/2022]
Abstract
PURPOSE Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). METHODS A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. FINDINGS The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. IMPLICATIONS After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.
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Affiliation(s)
| | | | - Yong Yuan
- Bristol-Myers Squibb, Princeton, New Jersey
| | | | | | | | - Fan Mu
- Analysis Group, Inc., Boston, Massachusetts
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22
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Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferrière V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB, Cohen J, Conway B, Cooper C, Côté P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis 2016; 62:919-926. [PMID: 26743093 PMCID: PMC4787608 DOI: 10.1093/cid/civ1222] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 11/18/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)-HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials. METHODS Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOTON-1 (NCT01667731), TURQUOISE-I (NCT01939197), ION-4 (NCT02073656), and ALLY-2 (NCT02032888) that evaluated simeprevir; sofosbuvir; ombitasvir, paritaprevir/ritonavir/dasabuvir; sofosbuvir/ledipasvir; and daclatasvir/sofosbuvir, respectively, to the Canadian Coinfection Cohort, representing approximately 23% of the total coinfected population in care in Canada. RESULTS Of 874 active participants, 70% had chronic HCV, of whom 410, 26, 94, and 11 had genotypes 1, 2, 3, and 4, respectively. After applying trial eligibility criteria, only 5.9% (24/410) would have been eligible for enrollment in the simeprevir trial, 9.8% (52/530) in PHOTON-1, 6.3% (26/410) in TURQUOISE-I, and 8.1% (34/421) in ION-4. The ALLY-2 study was more inclusive; 43% (233/541) of the cohort would have been eligible. The most exclusive eligibility criteria across all trials with the exception of ALLY-2 were restriction to specific antiretroviral therapies (63%-79%) and active illicit drug use (53%-55%). CONCLUSIONS DAA trial results may have limited generalizability, since the majority of coinfected individuals were not eligible to participate. Exclusions appeared to be related to improving treatment outcomes by not including those at higher risk of poor adherence and reinfection--individuals for whom real-world data are urgently needed.
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Affiliation(s)
- Sahar Saeed
- Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre.,Department of Epidemiology & Biostatistics
| | - Erin C Strumpf
- Department of Epidemiology & Biostatistics.,Department of Economics, McGill University, Montreal, Quebec
| | - Sharon L Walmsley
- Division of Infectious Diseases, Toronto Hospital, University Health Network, Ontario.,Canadian Institutes of Health Research, Canadian HIV Trials Network
| | - Kathleen Rollet-Kurhajec
- Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre
| | - Neora Pick
- Division of Infectious Diseases, Oak Tree Clinic, BC Women's Hospital, Vancouver, British Columbia
| | | | - Mark Hull
- Department of Infectious Disease, Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia
| | | | - Joseph Cox
- Department of Epidemiology & Biostatistics.,Public Health Department, Montreal Health and Social Services Agency, Quebec
| | - Curtis Cooper
- Department of Medicine, University of Ottawa, Ontario, Canada
| | - Marina B Klein
- Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, McGill University Health Centre.,Canadian Institutes of Health Research, Canadian HIV Trials Network
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23
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Huang QT, Huang Q, Zhong M, Wei SS, Luo W, Li F, Yu YH. Chronic hepatitis C virus infection is associated with increased risk of preterm birth: a meta-analysis of observational studies. J Viral Hepat 2015; 22:1033-42. [PMID: 26081198 DOI: 10.1111/jvh.12430] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 02/03/2015] [Indexed: 02/07/2023]
Abstract
Although several epidemiological studies reported that maternal chronic hepatitis C virus (HCV) infection had significantly increased risk of undergoing adverse obstetrical and perinatal outcomes, studies on the relationship between HCV infection and risk of preterm birth (PTB) have yielded inconclusive and inconsistent results. Therefore, we conducted a meta-analysis to investigate the association between HCV infection and PTB. The electronic database was searched until 1 September 2014. Relevant studies reporting the association between HCV infection and the risk of PTB were included for further evaluation. Statistical analysis was performed using revmen 5.3 and stata 10.0. Nine studies involving 4186698 participants and 5218 HCV infection cases were included. A significant association between HCV infection and PTB was observed (odds ratio = 1.62, 95% CI 1.48-1.76, P < 0.001, fixed-effects model). Stratification according to maternal smoking/alcohol abuse, maternal drug abuse or coinfected with HBV and/or HIV matched groups still demonstrated that women with HCV infection had a high risk for PTB. Findings from our meta-analysis suggested that maternal HCV infection was significantly associated with an increased risk of PTB. In the future, pathophysiological studies are warranted to ascertain the causality and explore the possible biological mechanisms involved.
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Affiliation(s)
- Q-t Huang
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | - Q Huang
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - M Zhong
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - S-s Wei
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - W Luo
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - F Li
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Y-h Yu
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Vedham V, Verma M, Mahabir S. Early-life exposures to infectious agents and later cancer development. Cancer Med 2015; 4:1908-22. [PMID: 26377256 PMCID: PMC4940808 DOI: 10.1002/cam4.538] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 08/11/2015] [Accepted: 08/14/2015] [Indexed: 12/13/2022] Open
Abstract
There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early‐life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma‐leukemia, nasopharyngeal carcinoma, and adult T‐cell leukemia‐lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV‐1) acquired in early life. For these agents, the acquisition in early life is from mother‐to‐child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development.
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Affiliation(s)
- Vidya Vedham
- Methods and Technologies Branch, National Cancer Institute, National Institutes of Health (NIH), 9609 Medical Center Drive, Rockville, Maryland, 20850
| | - Mukesh Verma
- Methods and Technologies Branch, National Cancer Institute, National Institutes of Health (NIH), 9609 Medical Center Drive, Rockville, Maryland, 20850
| | - Somdat Mahabir
- Environmental Epidemiology Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health (NIH), 9609 Medical Center Drive, Rockville, Maryland, 20850
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25
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Balagopal A, Barin B, Quinn J, Rogers R, Sulkowski MS, Stock PG. Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons. PLoS One 2015; 10:e0135882. [PMID: 26313939 PMCID: PMC4551738 DOI: 10.1371/journal.pone.0135882] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Accepted: 07/27/2015] [Indexed: 01/22/2023] Open
Abstract
Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210-429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7-4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02-0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01-4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.
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Affiliation(s)
- Ashwin Balagopal
- Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, United States of America
| | - Burc Barin
- The EMMES Corporation, Rockville, MD, 20850, United States of America
| | - Jeffrey Quinn
- Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, United States of America
| | - Rodney Rogers
- Department of Surgery, University of California San Francisco (UCSF), San Francisco, CA, 94122, United States of America
| | - Mark S. Sulkowski
- Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, United States of America
| | - Peter G. Stock
- Department of Surgery, University of California San Francisco (UCSF), San Francisco, CA, 94122, United States of America
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Johnson M, Borland J, Chen S, Savina P, Wynne B, Piscitelli S. Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. Br J Clin Pharmacol 2015; 78:1043-9. [PMID: 24838177 PMCID: PMC4243878 DOI: 10.1111/bcp.12428] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Accepted: 05/12/2014] [Indexed: 11/30/2022] Open
Abstract
AIMS The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. METHODS This was a single-centre, randomized, open-label, two-cohort, two-period, one-way study in healthy adult subjects. Dolutegravir 50 mg once daily was administered for 5 days in Period 1, and dolutegravir 50 mg once daily was coadministered with either boceprevir 800 mg every 8 h (Cohort 1) or telaprevir 750 mg every 8 h (Cohort 2) for 10 days in Period 2. RESULTS No deaths or serious adverse events were reported during the study. Four subjects were withdrawn from the study because of adverse events (elevated alanine aminotransferase, cellulitis, increased serum creatinine and dizziness). One subject became pregnant during the study. Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration-time curve (AUC) and maximal plasma concentration (Cmax ) and caused a small increase in concentration at the end of the dosing interval (Cτ ; 8%). Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone; AUC0- τ , Cmax and Cτ increased by 25, 19 and 37%, respectively. Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK. Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data, indicating no effect of dolutegravir on boceprevir or telaprevir exposure. CONCLUSIONS Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.
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Affiliation(s)
- Mark Johnson
- R&D Projects and Clinical Platforms, GlaxoSmithKline, Research Triangle Park, NC, USA
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27
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Hilgenfeldt EG, Schlachterman A, Firpi RJ. Hepatitis C: Treatment of difficult to treat patients. World J Hepatol 2015; 7:1953-63. [PMID: 26244069 PMCID: PMC4517154 DOI: 10.4254/wjh.v7.i15.1953] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 05/29/2015] [Accepted: 07/16/2015] [Indexed: 02/06/2023] Open
Abstract
Over the past several years, more so recently, treatment options for hepatitis C virus (HCV) have seemed to exponentially grow. Up until recently, the regimen of pegylated interferon (peg-IFN) and ribavirin (RBV) stood as the standard of care. Direct acting antivirals, which target nonstructural proteins involved in replication and infection of HCV were first approved in 2011 as an addition to the peg-IFN and RBV regimen and with them have come increased sustained virological response rates (SVR). The previously reported 50%-70% SVR rates using the combination of peg-IFN and RBV are no longer the standard of care with direct acting antiviral (DAA) based regimens now achieving SVR of 70%-90%. Peg-IFN free as well as "all oral" regimens are also available. The current randomized controlled trials available show favorable SVRs in patients who are naive to treatment, non-cirrhotic, and not human immunodeficiency virus (HIV)-co-infected. What about patients who do not fit into these categories? In this review, we aim to discuss the currently approved and soon to be approved DAAs while focusing on their roles in patients that are treatment experienced, cirrhotic, or co-infected with HIV. In this discussion, review of the clinical trials leading to recent consensus guidelines as well as discussion of barriers to treatment will occur. A case will attempt will be made that social services, including financial support and drug/alcohol treatment, should be provided to all HCV infected patients to improve chances of cure and thus prevention of late stage sequela.
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Affiliation(s)
- Eric G Hilgenfeldt
- Eric G Hilgenfeldt, Department of Internal Medicine, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Alex Schlachterman
- Eric G Hilgenfeldt, Department of Internal Medicine, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Roberto J Firpi
- Eric G Hilgenfeldt, Department of Internal Medicine, University of Florida College of Medicine, Gainesville, FL 32610, United States
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Toussaint-Miller KA, Andres J. Treatment Considerations for Unique Patient Populations With HCV Genotype 1 Infection. Ann Pharmacother 2015; 49:1015-30. [PMID: 26139639 DOI: 10.1177/1060028015592015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE To review the literature for the treatment of hepatitis C virus (HCV) genotype 1 in certain populations of patients that require further considerations before therapy initiation. DATA SOURCES A systematic electronic literature search using the MEDLINE database was performed using the search terms hepatitis C, chronic hepatitis C, drug therapy, end stage liver disease, liver transplantation, HIV, hepatitis B, African Americans, renal insufficiency, obesity, pregnancy, and pediatrics. STUDY SELECTION AND DATA EXTRACTION English language studies from January 1985 to March 2015 were considered. Additional references were identified from ongoing trials obtained from clinicaltrials.gov, conference proceedings, online databases, and citations in relevant review articles. DATA SELECTION Direct-acting antivirals are first-line recommendations for the treatment of HCV genotype 1 infection, and these include combinations of sofosbuvir, simeprevir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, and ribarvirin. Historical and clinical data focusing on the treatment of HCV with these agents in the following populations were selected: decompensated cirrhosis, post-liver transplant, HIV, African Americans, obesity, hepatitis B coinfection, renal impairment, pregnancy, and pediatrics. CONCLUSION Depending on the population studied, clinicians must consider differences in efficacy outcomes, potential drug interactions, and adverse effects that patients may experience.
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Prevalence and correlates of HCV monoinfection and HIV and HCV coinfection among persons who inject drugs in Vietnam. Eur J Gastroenterol Hepatol 2015; 27:550-6. [PMID: 25769097 PMCID: PMC4380662 DOI: 10.1097/meg.0000000000000321] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Vietnam bears a high burden of hepatitis C virus (HCV) and HIV infection among persons who inject drugs (PWID). The high prevalence of HCV and HIV occurs in a context of stigma and limited preventive interventions for PWID. OBJECTIVES This study aims to estimate the prevalence of HCV, HIV, and HIV/HCV coinfection among PWID and to explore their associations with lifetime injection behaviors. METHODS A total of 1434 PWID were recruited from the Thai Nguyen Province of Vietnam between 2005 and 2007. Participants responded to a structured questionnaire and provided blood samples at baseline. A cross-sectional analysis of data collected at baseline was carried out. Factors associated with HCV monoinfection and HIV/HCV coinfection were evaluated by multinomial logistic regression. RESULTS The prevalences of HIV and HCV were 35.1 and 88.8%, respectively, and the prevalences of HIV/HCV coinfection and HCV monoinfection were 34.8 and 53.9%, respectively. After adjusting for confounders in multivariate analysis, ever reusing a syringe and needle was found to be significantly associated with HIV monoinfection [adjusted odds ratio (AOR), 3.13; 95% confidence interval (CI), 1.99-4.94] and HIV/HCV coinfection (AOR, 3.34; 95% CI, 2.02-5.51). Ever sharing diazepam or novocaine was also found to be significantly associated with HIV monoinfection (AOR, 2.14; 95% CI, 1.38-3.32) and HIV/HCV coinfection (AOR, 2.47; 95% CI, 1.57-3.90). CONCLUSION Our findings demonstrate a high burden of HIV and HCV infection among PWID in Vietnam. Lifetime injection behaviors, including sharing of diazepam or novocaine, may account for the high prevalence of HIV and HCV. Improving prevention and ensuring access to care remain critically important for this vulnerable population.
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30
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Burgess S, Partovi N, Yoshida EM, Erb SR, Azalgara VM, Hussaini T. Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients. Ann Pharmacother 2015; 49:674-87. [PMID: 25770114 DOI: 10.1177/1060028015576180] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.
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Affiliation(s)
- Sarah Burgess
- University of British Columbia, Vancouver, BC, Canada
| | - Nilufar Partovi
- University of British Columbia, Vancouver, BC, Canada Vancouver General Hospital, Vancouver, BC, Canada
| | - Eric M Yoshida
- University of British Columbia, Vancouver, BC, Canada Vancouver General Hospital, Vancouver, BC, Canada
| | - Siegfried R Erb
- University of British Columbia, Vancouver, BC, Canada Vancouver General Hospital, Vancouver, BC, Canada
| | - Vladimir Marquez Azalgara
- University of British Columbia, Vancouver, BC, Canada Vancouver General Hospital, Vancouver, BC, Canada
| | - Trana Hussaini
- University of British Columbia, Vancouver, BC, Canada Vancouver General Hospital, Vancouver, BC, Canada
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Xia Y, Friedmann P, Yaffe H, Phair J, Gupta A, Kayler LK. Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses. Am J Transplant 2014; 14:2037-47. [PMID: 25098499 DOI: 10.1111/ajt.12847] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Revised: 03/21/2014] [Accepted: 03/27/2014] [Indexed: 01/25/2023]
Abstract
Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival.
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Affiliation(s)
- Y Xia
- Department of Surgery, Montefiore Medical Center, Bronx, NY; Department of Surgery, Albert Einstein College of Medicine, Bronx, NY
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Abstract
Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed.
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Affiliation(s)
- Cody A Chastain
- Division of Infectious Diseases, Vanderbilt University Medical Center, A-2200 MCN, 1161 21st Avenue, Nashville, TN, 37232-2582, USA,
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Rohrbach J, Stickel F, Schmid P, Thormann W, Kovari H, Scherrer A, Günthard HF, Vuichard D, Cavassini M, Ambrosioni J, Bernasconi E, Furrer H, Rauch A. Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals. Antivir Ther 2013; 19:149-59. [PMID: 24036684 DOI: 10.3851/imp2686] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND We investigated changes in biomarkers of liver disease in HIV-HCV-coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV infection and to HIV-monoinfected individuals. METHODS Non-invasive biomarkers of liver disease (hyaluronic acid [HYA], aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 [FIB-4] index and cytokeratin-18 [CK-18]) were correlated with liver histology in 49 HIV-HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV-HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on cART. All analyses were conducted before starting HCV treatment. RESULTS Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR stage (P<0.002 for all comparisons). The mean ±sd area under the receiver operating characteristic (AUROC) curve values for advanced fibrosis (≥F3 METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86 ±0.05, 0.84 ±0.08, 0.80 ±0.09 and 0.81 ±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV-HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, respectively; P=0.1), mainly due to the reversion of HIV-induced thrombocytopaenia, whereas HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed <3% during untreated HIV-infection. Overall, 3 patients died from end-stage liver disease, and 10 from other causes. CONCLUSIONS Biomarkers of liver disease highly correlated with fibrosis in HIV-HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV-HCV-coinfected individuals, at least during successful cART.
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Affiliation(s)
- Janine Rohrbach
- Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
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Vedham V, Divi RL, Starks VL, Verma M. Multiple infections and cancer: implications in epidemiology. Technol Cancer Res Treat 2013; 13:177-94. [PMID: 23919392 DOI: 10.7785/tcrt.2012.500366] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Approximately 18% of the global cancer burden has been attributed to infectious agents, with estimates ranging from 7% in developed countries to about 22% in developing countries. Chronic infections caused by the hepatitis B and C viruses, human papilloma viruses (HPV), and Helicobacter pylori (H. pylori) are reported to be responsible for approximately 15% of all human cancers. Interestingly, although many of the infectious agents that have been associated with cancer--such as HPV, Epstein-Barr virus (EBV), and H. pylori--are highly prevalent in the world, most infected individuals do not develop cancer but remain lifelong carriers. Malignancies associated with infectious agents may result from prolonged latency as a result of chronic infections. Pathogenic infections are necessary but are not sufficient for cancer initiation or progression. Cancer initiation may require additional cofactors, including secondary infections. Therefore, in patients with chronic infection with one agent, secondary co-infection with another agent may serve as an important co-factor that may cause cancer initiation and progression. Additionally, opportunistic co-infections could significantly inhibit response to cancer treatment and increase cancer mortality. Co-infections are relatively common in areas with a high prevalence of infectious agents, especially in developing countries. These co-infections can cause an imbalance in the host immune system by affecting persistence of and susceptibility to malignant infections. Several articles have been published that focus on infectious agents and cancer. In this article, we discuss the role of infectious agents in malignancies, highlight the role of multiple/co-infections in cancer etiology, and review implications for cancer epidemiology.
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Affiliation(s)
- Vidya Vedham
- Methods and Technologies Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health (NIH), 6130 Executive Boulevard, Suite 5100, Bethesda, MD 20892-7324, USA.
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Dimitroulis D, Valsami S, Spartalis E, Pikoulis E, Kouraklis G. Hepatocellular carcinoma in patients co-infected with hepatitis C virus and human immunodeficiency virus. World J Hepatol 2013; 5:323-327. [PMID: 23805356 PMCID: PMC3692973 DOI: 10.4254/wjh.v5.i6.323] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Revised: 04/17/2013] [Accepted: 05/10/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share a common route of transmission so that about one third of HIV infected individuals show HCV co-infection. Highly active antiretroviral therapy has offered a longer and better life to infected patients. While has removed AIDS-related diseases from the list of most common causes of death their place has been taken by complications of HCV infection, such as cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC). HIV/HCV co-infection requires complex management, especially when HCC is present. Co-infected patients with HCC undergo the same therapeutic protocol as their mono-infected counterparts, but special issues such as interaction between regimens, withdrawal of therapy and choice of immunosuppressive agents, demand a careful approach by specialists. All these issues are analyzed in this minireview.
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A Simple and Rapid Method for the Detection of HIV-1/HCV in Co-Infected Patients. IRANIAN JOURNAL OF BIOTECHNOLOGY 2013. [DOI: 10.5812/ijb.10717] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct-acting antiviral drugs in the HIV-positive patient. Curr Opin Infect Dis 2013; 26:50-7. [PMID: 23242341 DOI: 10.1097/qco.0b013e32835c2027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PURPOSE OF REVIEW Successful treatment of hepatitis C virus (HCV) infection is necessary for the survival of HIV-infected patients. This review covers the outcomes of current therapy, first-generation HCV direct-acting antivirals (DAAs) and their drug-to-drug interactions (DDIs). Understanding DDIs between HIV antiretroviral therapy (ART) and the DAAs in development is important to assure the best management of the HIV/HCV coinfected individuals. RECENT FINDINGS The two first-in-class DAAs were approved for clinical use in 2011. The first trials with boceprevir or telaprevir added to standard therapy in HIV/HCV coinfected patients revealed triple therapy to be efficacious with significantly improved sustained virological response rates. However, these DAAs were associated with more and worse adverse effects, as well as with significant DDIs with multiple drugs, including ART. Early data on DAAs in development suggest improved efficacy and safety and the potential for lesser DDIs. SUMMARY Anti-HCV therapy is fundamental in coinfected patients, but the approved therapies are suboptimal. The first-generation of approved HCV DAAs improved efficacy of therapy in coinfected patients, but have multiple safety concerns, including potentially serious drug interactions with ART. Early results from newer DAAs are promising.
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Feijoo J, Eirea M, Limeres J, Abeleira M, Ramos I, Ocampo A, Diz P. HCV clearance from saliva of HIV-HCV-coinfected patients on treatment with interferon plus ribavirin. Oral Dis 2013; 20:313-8. [PMID: 23607445 DOI: 10.1111/odi.12116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Revised: 03/27/2013] [Accepted: 04/04/2013] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To determine hepatitis C virus (HCV) RNA clearance from blood and saliva of HIV-HCV-coinfected patients undergoing combined therapy with pegylated interferon plus ribavirin (PEG-IFN-RIB). SUBJECTS AND METHODS Study group was formed of 60 HIV-infected patients with chronic hepatitis C who were starting treatment with PEG-IFN-RIB. Blood and saliva samples were taken at baseline, at the end of treatment and 24 and 48 weeks later. A nested RT-PCR technique was used to detect HCV-RNA in saliva. RESULTS HCV-RNA was detected in saliva at baseline in 64.7% of patients. Thirty-four patients completed follow-up. The response rate (undetectable HCV-RNA) in blood was 79.4% at the end of treatment; 55.8% at 24 weeks after the end of treatment and 50% at 48 weeks. HCV was detected in saliva of 13 (38.2%) patients at the end of treatment and in 18 (52.9%) patients at 24 and 48 weeks later. Concordance of HCV clearance from blood and saliva reached its maximum value at 48 weeks after the end of treatment (odds ratio, 112.51). CONCLUSION In HIV-HCV-coinfected patients responders to PEG-IFN-RIB, the salivary glands do not appear to be a sanctuary site for HCV, although viral clearance from saliva may be slower than from blood.
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Affiliation(s)
- J Feijoo
- Grupo de Investigación en Odontología Médico-Quirúrgica (OMEQUI), School of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
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Sulkowski MS. Current management of hepatitis C virus infection in patients with HIV co-infection. J Infect Dis 2013; 207 Suppl 1:S26-32. [PMID: 23390302 DOI: 10.1093/infdis/jis764] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
As a result of shared routes of transmission, coinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)-infected patients. The prevalence of HIV/HCV coinfection is particularly high among persons who have used injection drugs; however, more recently, sexual transmission of HCV has been recognized among HIV-infected men who have sex with men (MSM). Over the past decade, the effectiveness of HIV treatment improved substantially, leading to a substantial reduction in HIV/AIDS-related deaths; in this context, liver disease due to HCV infection has emerged as major concern for co-infected patients. Over the same period, treatment of HCV remained stagnant, with pegylated interferon alfa (PegIFN) plus ribavirin (RBV; PegIFN/RBV) entrenched as the standard treatment for HCV infection for co-infected patients, who have the greatest risk for liver disease. However, the effectiveness of HCV treatment in this population has been disappointing because of low rates of treatment initiation and success. In 2011, novel HCV NS3/4A PIs (PIs), telaprevir and boceprevir, were approved for use in combination with PegIFN/RBV for the treatment of HCV genotype 1 infection; at the time of approval, important questions regarding the efficacy, safety, and potential for drug interactions with telaprevir and boceprevir had not been answered. More recently, data from drug-interaction studies and 2 small, phase II clinical trials indicate that these HCV treatment regimens may lead to higher rates of HCV eradication in HIV/HCV-coinfected patients, with manageable toxicity and pharmacologic interactions with antiretroviral drugs. As such, these HCV PI-based regimens have emerged as the standard for the treatment of HCV genotype 1 infection in carefully selected HIV-infected patients.
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Affiliation(s)
- Mark S Sulkowski
- Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
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Kang F, Chen W, Zhang X, Nie W, Fu J, Xu X, Zhao P, Zhang X, Li W, Wang FS, Zhang Z, Zhao M. Transient liver injury associated with the early recovery of HCV-specific T-cell responses and HCV rebound in HIV-1/HCV coinfected patients undergoing highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2013; 62:135-42. [PMID: 23075912 DOI: 10.1097/qai.0b013e3182752d20] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES HIV-1/hepatitis C virus (HCV) coinfection accelerates the progression of liver disease to cirrhosis, particularly in individuals with low CD4 T-cell counts. Highly active antiretroviral therapy (HAART) can significantly increase HCV-specific T-cell responses; however, it remains unclear whether the restoration of HCV-specific T cells by HAART is associated with liver injury in these coinfection patients. METHODS A total of 32 HIV-1/HCV coinfected patients and 14 HCV monoinfected patients were enrolled, and 13 coinfected patients were initialized HAART and followed up for 6 months. HCV-specific interferon-γ responses to HCV core and NS3A proteins were examined by enzyme-linked immunosorbent spot. RESULTS HCV-specific interferon-γ responses to HCV core and NS3A proteins were impaired in HIV-1/HCV-coinfected patients as compared with those in HCV monoinfected patients. The impaired HCV-specific T-cell responses could be efficiently restored during the early phase of HAART, independent of HCV status, and were positively associated with increased CD4 T-cell counts. In addition, this recovery of HCV-specific T-cell responses occurred simultaneously with elevated serum alanine aminotransferase levels in HCV viremic patients and in patients with HCV rebound, but not in HCV nonviremic patients after 6 months of HAART. CONCLUSIONS The recovery of HCV-specific T-cell responses by HAART may lead to transient liver injury in patients with HIV-1/HCV coinfection, suggesting that early anti-HCV therapy before HAART may reduce the risk of liver injury and therefore may be beneficial to HIV-1/HCV-coinfected patients.
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Affiliation(s)
- Fubiao Kang
- The Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
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Optimizing hepatitis C therapy in HIV/hepatitis C virus (HCV) coinfected patients: Analysis of HCV viral kinetics on treatment. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2013; 23:31-5. [PMID: 23450124 DOI: 10.1155/2012/384630] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. METHODS Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. RESULTS There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. DISCUSSION High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy. INTRODUCTION Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. METHODS Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. RESULTS There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. DISCUSSION High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.
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Imami N, Westrop SJ, Grageda N, Herasimtschuk AA. Long-Term Non-Progression and Broad HIV-1-Specific Proliferative T-Cell Responses. Front Immunol 2013; 4:58. [PMID: 23459797 PMCID: PMC3585435 DOI: 10.3389/fimmu.2013.00058] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Accepted: 02/17/2013] [Indexed: 12/30/2022] Open
Abstract
Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1(+) patients during early stages of disease, and are maintained in long-term non-progressing subjects. In the vast majority of HIV-1(+) patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilizing cure, involving clearance of virus from the host, remains a primary aim, a "functional cure" may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilized in future strategies designed to improve upon existing therapy. The aim will be to induce long-term non-progressor or elite controller status in every infected host, through immune-mediated control of viremia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.
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Affiliation(s)
- Nesrina Imami
- Department of Medicine, Imperial College LondonLondon, UK
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Hull M, Klein M, Shafran S, Tseng A, Giguère P, Côté P, Poliquin M, Cooper C. CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2013; 24:217-38. [PMID: 24489565 PMCID: PMC3905006 DOI: 10.1155/2013/781410] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale. RESULTS All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients. DISCUSSION Recommendations may not supersede individual clinical judgement.
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Affiliation(s)
- Mark Hull
- University of British Columbia, British Columbia Centre for Excellent in HIV/AIDS, Vancouver, British Columbia
| | | | | | | | | | - Pierre Côté
- Clinique médicale du Quartier Latin, Montréal, Quebec
| | - Marc Poliquin
- Clinique médicale du Quartier Latin, Montréal, Quebec
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Lambotin M, Barth H, Moog C, Habersetzer F, Baumert TF, Stoll-Keller F, Fafi-Kremer S. Challenges for HCV vaccine development in HIV-HCV coinfection. Expert Rev Vaccines 2012; 11:791-804. [PMID: 22913257 DOI: 10.1586/erv.12.52] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is estimated that 4-5 million HIV-infected patients are coinfected with HCV. The impact of HIV on the natural course of HCV infection is deleterious. This includes a higher rate of HCV persistence and a faster rate of fibrosis progression. Coinfected patients show poor treatment outcome following standard HCV therapy. Although direct antiviral agents offer new therapeutic options, their use is hindered by potential drug interactions and toxicity in HIV-infected patients under HAART. Overtime, a large reservoir of HCV genotype 1 patients will accumulate in resource poor countries where the hepatitis C treatment is not easily affordable and HIV therapy remains the primary health issue for coinfected individuals. HCV vaccines represent a promising strategy as an adjunct or alternative to current HCV therapy. Here, the authors review the pathogenesis of hepatitis C in HIV-infected patients, with a focus on the impact of HIV on HCV-specific immune responses and discuss the challenges for vaccine development in HIV-HCV coinfection.
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Gagneux-Brunon A, Mariat C, Delanaye P. Cystatin C in HIV-infected patients: promising but not yet ready for prime time. Nephrol Dial Transplant 2012; 27:1305-13. [DOI: 10.1093/ndt/gfs001] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Exploiting the anti-HIV-1 activity of acyclovir: suppression of primary and drug-resistant HIV isolates and potentiation of the activity by ribavirin. Antimicrob Agents Chemother 2012; 56:2604-11. [PMID: 22314523 DOI: 10.1128/aac.05986-11] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Multiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infected ex vivo. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings.
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Abstract
As a result of shared modes of transmission, chronic hepatitis C infection is common in HIV-infected patients, particularly among those who have used injection drugs as well as men who have sex with men (MSMs). In the era of effective antiretroviral therapy, HCV infection has emerged as a major cause of morbidity and mortality worldwide. Over the last decade, treatment with peginterferon (PEG-IFN) plus ribavirin (RBV) has been recommended for coinfected patients who are at the greatest risk for liver disease; however, the effectiveness of HCV treatment in this population has been disappointing. Challenges to the use of HCV NS3/4A protease inhibitors, telaprevir and boceprevir, patients with HIV/HCV coinfection include the potential for interactions between different drugs, addition of drug toxicities, and the need for therapy with PEG-IFN. Despite these challenges, limited data indicate that telaprevir and boceprevir given in combination with PEG-IFN/RBV increase the rate of viral suppression in coinfected patients with manageable toxicity and drug-drug interaction profile. Accordingly, these agents may be recommended for HCV treatment in carefully selected HIV-infected persons.
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Affiliation(s)
- Mark S Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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48
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Di Biagio A, Rosso R, Viscoli C, Loregian A, Pagni S, Palù G, Sormani MP, Cenderello G. Effects of hepatitis C virus infection on the pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected patients. J Infect Chemother 2012; 18:587-90. [DOI: 10.1007/s10156-012-0402-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Accepted: 02/23/2012] [Indexed: 01/24/2023]
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49
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Peña-Orellana M, Hernández-Viver A, Caraballo-Correa G, Albizu-García CE. Prevalence of HCV risk behaviors among prison inmates: tattooing and injection drug use. J Health Care Poor Underserved 2011; 22:962-82. [PMID: 21841290 DOI: 10.1353/hpu.2011.0084] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Hepatitis C virus (HCV) is the most common blood-borne chronic viral infection in the United States and it is over represented in incarcerated populations. This study estimates if in prison tattooing is associated with self reported HCV infection in a probabilistic sample of 1,331 sentenced inmates in Puerto Rico prisons anonymously surveyed in 2004, who had previously been tested for HCV. Analysis were carried out with the total sample and among non-injectors (n=796) to control for injection drug use (IDU) and other confounders. Nearly 60% of inmates had acquired tattoos in prison. HCV was reported by 27% of subjects in the total sample and by 12% of non-injectors who had undergone tattoos in prison. IDU was the strongest predictor of HCV in the total sample (OR=5.6, 95% CI=3.2-9.7). Among non injectors, tattooing with reused needles or sharp objects and/ or reusing ink was positively associated with HCV self-report (OR=2.6, 95% CI=1.3-5.5). Tattooing is a common occurrence in this prison setting. Findings suggest that preventive interventions are required to reduce the risk of HCV transmission through unsterile tattooing and injection practices.
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Affiliation(s)
- Marisol Peña-Orellana
- Center for Evaluation and Sociomedical Research, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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50
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Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus coinfection with special reference to hemophiliac recipients in Japan. Surg Today 2011; 41:1325-31. [PMID: 21922353 DOI: 10.1007/s00595-010-4556-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Accepted: 11/09/2010] [Indexed: 10/17/2022]
Abstract
Liver transplantation for patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) remains challenging. The advent of highly active antiretroviral therapy (HAART) for HIV has reduced mortality from opportunistic infection related to acquired immunodeficiency syndrome dramatically, while about 50% of patients die of end-stage liver cirrhosis resulting from HCV. In Japan, liver cirrhosis frequently develops after HCV-HIV coinfection resulting from previously transfused infected blood products for hemophilia. The problems of liver transplantation for those patients arise from the need to control calcineurin inhibitor with HAART drugs, the difficulty of using interferon after liver transplantation with HAART, and the need to control intraoperative coagulopathy associated with hemophilia. We review published reports of liver transplantation for these patients in the updated world literature.
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