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Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men.

ABSTRACT: There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal.We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment.In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ?12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens.Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic.

SUBMITTER: Fierer DS

PROVIDER: S-EPMC3935497 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men.

Fierer Daniel S DS Dieterich Douglas T DT Mullen Michael P MP Branch Andrea D AD Uriel Alison J AJ Carriero Damaris C DC van Seggelen Wouter O WO Hijdra Rosanne M RM Cassagnol David G DG

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20131213 6

<h4>Background</h4>There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal.<h4>Methods</h4>We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavi ...[more]

PMID: 24336914

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Project description:BACKGROUND:We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex with men. METHODS:One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100000 per quality-adjusted life-year (QALY) gained. RESULTS:All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor-based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ?1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. CONCLUSIONS:Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence, regular screening with LFTs, with or without an HCV Ab test, is the optimal strategy.

Project description:BACKGROUND:Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. METHODS:We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. RESULTS:Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. CONCLUSIONS:Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.

Project description:BackgroundPatients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.MethodsWe enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.ResultsOf the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).ConclusionsIn this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.).

Project description:BackgroundOutbreaks of sexually transmitted hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)-infected men who have sex with men in Europe, Australia, and New York. Whether this is occurring across the United States is unknown.MethodsWe determined incidence of HCV infection during 1996-2008 among male participants of the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials cohort, a long-term study of HIV-infected persons randomized into selected US-based clinical trials. We evaluated associations with self-reported injection drug use (IDU), time-varying CD4(+) cell count, and HIV RNA level with use of multivariate Poisson regression. No sexual or non-IDU risk factor data was available.ResultsA total of 1830 men had an initial negative HCV antibody test result and at least 1 subsequent HCV antibody test result, contributing >7000 person-years. At the time of the initial negative HCV antibody test result, 94% of men were receiving highly active antiretroviral therapy (HAART) and 6% reported current or prior IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100 person-years (95% confidence interval, .36-.70). Mean age at seroconversion was 46 years. Seroconversion was associated with IDU (25% of seroconverters reported IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity vs 21% at time of last negative antibody test result; P = .02) but not with CD4(+) cell count.ConclusionsIncident HCV infection occurs in HIV-infected men involved in US HIV therapeutic trials, primarily through nonparenteral means, despite engagement in care and HAART. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression. At-risk HIV-infected persons should have access to HCV surveillance.

Project description:OBJECTIVE:An epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance. METHODS:This prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Mary's Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR = 29-69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene. RESULTS:15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of 'fluctuating' progressors (37.5%), in whom a fall followed by a rise (>1 log??) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log?? viral load drop within 100 days of infection (HR = 1.78; p < 0.0001), elevated bilirubin (? 40 ?mol/l; HR = 5.04; p = 0.006), elevated alanine aminotransferase (ALT; ? 1000 IU/ml; HR = 2.62; p = 0.048) and baseline CD4 count ? 650 × 10?/l (HR = 2.66; p = 0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response. CONCLUSIONS:Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.

Dataset Information

Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men.

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Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men.

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