Approximately 10% of HIV-seropositive individuals are co-infected with hepatitis C virus (HCV). Co-infection with HCV and HIV is particularly prevalent among HIV-seropositive injecting drug users. The course of chronic hepatitis C is more severe in HIV-seropositive patients than in HIV-seronegative individuals. Given the poor efficacy of IFN-α monotherapy in co-infected patients and the promising results of combination therapy with IFN and ribavirin in immunocompetent HIV-seronegative patients  we have engaged in the treatment with IFN and ribavirin of a cohort of HIV-seropositive patients with chronic hepatitis C in an open prospective trial.
Among the 46 patients so far enrolled in the study, four patients were na]ve of antiretroviral treatment (Table 1). Two of these patients had failed to respond to IFN and ribavirin at 36 weeks, whereas the two other patients were complete responders to therapy, as assessed by the lack of detectable circulating HCV RNA using the Amplicor Roche assay with a lower detection limit of 1000 copies/ml. Plasma levels of HIV RNA of the four patients, before the initiation of IFN and ribavirin, were 4.48 and 4.45 log copies/ml (Quantiplex HIV-RNA 2.0, threshold: 500 copies/ml; Chiron, Emeryville, CA, USA). At week 36 of IFN and ribavirin, the plasma levels of HIV RNA of the two responding patients decreased significantly to 1.79 and 1.76 log copies/ml, with a concomittant increase in the CD4 cells from 565 and 432 to 623 and 584 × 106/l, in the absence of antiretroviral treatment. In the two non-responding patients, plasma levels of HIV RNA (3.8 and 2.9 copies/ml) and CD4 cell counts (398 and 367 × 106/l) at 6 months of therapy did not differ from those at baseline.
Ribavirin is a nucleoside analogue that exhibited a poor antiviral activity against HIV in one previous clinical trial  IFN-α alone was also shown not to be an effective therapy for HIV disease. Facilitating interactions between hepatitis B virus (HBV) and HIV  and between HCV and HBV replication  through transactivation of viral genes, have been reported; however, there is no such report for HCV and HIV.
Our observations suggest a beneficial effect of IFN and ribavirin on plasma levels of HIV RNA in HIV-seropositive patients with moderate immunodeficiency, co-infected with HCV. Because immune reconstitution with highly active antiretroviral therapy has been associated with enhanced liver damage in co-infected patients with chronic hepatitis C, our data may encourage clinicians to delay the time of initiation of antiretroviral therapy in HIV-seropositive patients with chronic hepatitis C, in order first to achieve a remission of HCV disease. Future trials are needed to confirm these results and document the safety and efficacy of combination therapy with IFN and ribavirin in patients co-infected with HIV and HCV.
Michel D. Kazatchkine
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