Sustained Long-Term Antiviral Maintenance Therapy in HCV/HIV-Coinfected Patients (SLAM-C)

Abstract

Background HCV/HIV coinfection treatment is suboptimal with low SVR rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated-interferon maintenance therapy was performed by the NIH-funded ACTG network. Methods HCV treatment naïve and non-responding interferon-experienced subjects with confirmed HCV and HIV, CD4>200 cells/mm3, and at least Stage 1 fibrosis were enrolled, and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg/week (PEG) + weight-based ribavirin to determine response status. Non-responder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist. Results 330 subjects were enrolled; median age was 48 years; 43% White, 37% Black, non-Hispanic; 83% male; CD4+ 498 cells/mm3; 32% were interferon experienced; 74% had entry HIV RNA<50 cp/ml. EVR was observed in 55.9% and 42.5% achieved cEVR. A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm. Conclusion Lack of fibrotic progression in the control arm was unexpected, and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression and use of antiretroviral regimens that may be less toxic than prior generations of therapy.

Chronic Liver Disease in the Hispanic Population of the United States

“…Furthermore, ethnic variations in response to anti-HCV therapy in HIV-infected individuals have also been described. For example, Sherman et al 73 assessed early virologic response (EVR), an accurate predictor of SVR, in HIV/HCV coinfected patients. Similar to HCV mono-infected individuals, Hispanic and African American individuals coinfected with HIV were much less likely than NHW individuals to achieve early virologic response after 12 weeks of therapy with pegylated interferon and ribavirin (56% vs 42.3% vs 65.5%, respectively).…”

Randomized clinical trial

“…The lead-in phase of treatment was postulated to be one of the explanations for the lack of fibrosis progression in the control arm of the SLAM-C study [30]. In this trial, patients with HCV and HIV coinfection who were previous nonresponders to HCV eradication therapy were randomized to receive 96 weeks of PEG-IFN therapy or observation after a 12-week lead-in treatment phase.…”

Current treatment for chronic hepatitis C virus/HIV-infected individuals

“…This finding begs the question -does peg-IFN therapy have histological benefit in patients not clearing HCV? The multicentre SLAM-C study [20] examined this hypothesis by randomizing nonresponder patients (failure to clear HCV RNA or achieve a 2-log reduction in HCV RNA after 12 weeks of peg-IFN/RBV) to continued peg-IFN or observation for a total of 72 weeks. The study was stopped following an interim analysis due to lack of fibrosis progression in the control arm.…”