Treatment of hepatitis C in HIV-infected patients: regularly reassess the benefits and risks.
(1) HIV-infected patients appear to be at an increased risk of complications of hepatitis C virus (HCV) infection. (2) Treatments for hepatitis C have been assessed in four open-label randomised controlled trials involving more than 1500 HIV-infected patients. Only virological endpoints were assessed. Patients with low CD4 lymphocyte counts were excluded, and few patients had cirrhosis. (3) Only one of these trials compared ribavirin versus placebo in combination with peginterferon alfa-2a. The addition of ribavirin increased the antiviral efficacy of interferon: 40% of the patients receiving ribavirin had no detectable virus at 24 weeks after the end of treatment versus 12% of patients in the placebo group. (4) The four trials compared peginterferon alfa-2 (a or b) with interferon alfa-2 (a or b) in combination with ribavirin. The results of the four trials were similar: overall, significantly more patients infected with HCV genotype 1, 2, or 3 on peginterferon alfa-2 (26-44%) than on standard interferon alfa-2 (18-21%) had no detectable virus at 24 weeks. However, treatment was more effective in patients infected with genotype 2 or 3 (44-62% of patients without detectable virus) than in patients infected with genotype 1 (17-29%). These results appear to be less favourable than those obtained in other studies of HIV-seronegative patients. (5) In the short term, virological efficacy seems to be associated with a lower frequency of histological progression, but this is based on an analysis of only half the patients enrolled in a single trial. (6) The proportion of withdrawals for adverse events with peginterferon alfa-2 + ribavirin treatment ranged from 4% to 15%, depending on the trial. (7) The CD4 cell count fell by about 140/mm3 on average during peginterferon alfa-2a + ribavirin therapy. One patient died after a particularly sharp drop. (8) Treatment of hepatitis C appears to increase the risk of lactic acidosis associated with antiretroviral drugs (especially didanosine). (9) In practice, HIV/HCV coinfected patients treated for hepatitis C must receive close clinical and laboratory monitoring, and the individual risk-benefit balance must be regularly assessed. Clinical trial data available in early 2005 do not show whether the benefits of treatment for hepatitis C outweigh the risks in patients with mild hepatic fibrosis, cirrhosis, or a low CD4 cell count.
D000140:Acidosis, Lactic / Q000139:chemically induced; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005355:Fibrosis / Q000188:drug therapy; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin