Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C)

J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):597-605. doi: 10.1097/QAI.0b013e3181f6d916.

Abstract

Background: Hepatitis C virus (HCV)/HIV coinfection treatment is suboptimal with low sustained viral response rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated interferon maintenance therapy was performed by the National Institutes of Health-funded AIDS Clinical Trials Group network.

Methods: HCV treatment-naive and nonresponding interferon-experienced subjects with confirmed HCV and HIV, CD4 >200 cells per cubic millimeter, and at least stage 1 fibrosis were enrolled and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg per week (PEG) + weight-based ribavirin to determine response status. Nonresponder 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: Three hundred thirty subjects were enrolled; median age was 48 years; 43% white, 37% black, non-Hispanic; 83% male; CD4+ 498 cells per cubic millimeter; 32% were interferon experienced; 74% had entry HIV RNA <50 copies per milliliter. early virologic responder was observed in 55.9% and 42.5% achieved complete Early Viral Response (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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00078403.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Hepacivirus / drug effects
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Liver / physiopathology
  • Liver / virology
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00078403

Grant support