Background

Complications of hepatitis C increasingly contribute to morbidity and mortality in patients coinfected with HIV and hepatitis C virus (HCV). Two randomized trials presented final efficacy and safety results on the treatment of chronic HCV in coinfected individuals.

A Randomized, Controlled Trial of PEG-Interferon-alfa-2a plus Ribavirin vs Interferon-alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV-co-infected Persons: Follow-up Results of ACTG A5071

Abstract: Chung R, Andersen J, Volberding P, et al. A Randomized, Controlled Trial of PEG-Interferon-alfa-2a plus Ribavirin vs Interferon-alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV-co-infected Persons: Follow-up Results of ACTG A5071. 11th CROI, Abstract 110.

Description: ACTG A5071 randomized 133 subjects with compensated liver disease and stable HIV disease to 48 weeks of treatment with peginterferon-alpha-2a (PEG-IFN) or interferon-alpha-2a (IFN). Subjects in both arms received ribavirin (RBV), with dose escalation from 600 mg/day to 1000mg/day. Subjects were well matched for baseline HIV and HCV characteristics: 77-78% had HCV genotype 1; 9-11% had cirrhosis; 60% had HIV viral loads <50 copies/mL; and median CD4 count was 444-492 cells/mm³.

Results: The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA six months after completion of therapy.

In each study arm, 12% of participants discontinued treatment because of adverse effects.

Positive predictors of SVR, by multivariable analysis, were treatment with PEG-IFN/RBV, genotype other than 1, no prior injection drug use, and detectable HIV RNA at baseline. Age, race, CD4 count, and use of antiretroviral therapy were not associated with response to treatment. Virologic nonresponse at 12 weeks (defined as <2-log decrease in HCV RNA) predicted failure to achieve SVR in 100% of cases. However, histological improvement was seen in 36% of virologic nonresponders. CD4 counts decreased during treatment but returned to baseline during the follow-up period; no loss of HIV virologic control was seen.

Final Results of APRICOT: A Randomized, Partially Blinded, International Trial Evaluating Peginterferon-alfa-2a + Ribavirin vs Interferon-alfa-2a + Ribavirin in the Treatment of HCV in HIV/HCV Co-infection

Abstract: Torriani F, Rockstroh J, Rodriguez-Torres M, et al. Final Results of APRICOT: A Randomized, Partially Blinded, International Trial Evaluating Peginterferon-alfa-2a + Ribavirin vs Interferon-alfa-2a + Ribavirin in the Treatment of HCV in HIV/HCV Co-infection. 11th CROI, Abstract 112.

Description: The APRICOT study randomized 860 patients with stable liver function and HIV disease to 48 weeks of treatment with one of three regimens: interferon-alpha-2a (IFN) plus ribavirin (RBV), peginterferon-alpha-2a (PEG-IFN) plus placebo, or PEG-IFN plus RBV. Ribavirin was dosed at 800 mg/day. The treatment arms were well matched for baseline HCV and HIV characteristics. 60-61% of subjects had HCV genotype 1, and 15-16% had cirrhosis. The mean CD4 count was 520-540 cells/mm³, the median HIV viral load was 2.3 log10 copies/mL, and 86% of patients were on antiretroviral therapy.

Results: The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA six months after completion of therapy.

Approximately 15% of subjects in each study arm discontinued treatment due to adverse effects. CD4 counts decreased during treatment but returned to baseline after completion of HCV therapy; HIV RNA remained stable in those with undetectable viral load and decreased in those treated with PEG-IFN who had detectable viremia at baseline.

Comment: Taken together, these studies suggest that the most effective treatment of HCV in coinfected patients is peginterferon-alpha-2a plus ribavirin, although optimal formulations and dosing strategies remain to be determined. Response to treatment for HCV was poor in coinfected patients with genotype 1. HCV treatment was found to have no lasting negative impact on laboratory correlates of HIV disease. While the APRICOT study showed better outcomes than the ACTG study, perhaps related to the higher initial dose of ribavirin used, specific patient characteristics that may be associated with improved treatment results, such as stage of HCV and of HIV infection, remain to be elucidated.