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Excerpt
The combination of IFN-α with ribavirin resulted in a significantly improved response rate in HIV-negative patients [7,8]. This therapeutic strategy has therefore been proposed in HIV-1-positive patients chronically infected with HCV.
Ribavirin has no direct antiviral effect on either HIV-1 or HCV infection [9–11]. A number of studies [12,13] indicated that ribavirin may inhibit in vitro the phosphorylation of potent inhibitors (pyrimidine analogues) of HIV-1 reverse transcriptase such as zidovudine (ZDV), stavudine (d4T) and lamivudine (3TC). These findings obtained in vitro suggest that the administration of ribavirin in combination with these antiretroviral agents could affect the efficacy of anti-HIV therapy in vivo.
To examine the effect of ribavirin on the efficacy of anti-HIV therapy in vivo, we prospectively studied virological and immunological parameters in 12 HIV-positive patients (seven men, five women; mean age 38 years, range 27–51) treated with ribavirin and IFN-α for chronic hepatitis C, under an antiretroviral regimen that included pyrimidine analogues (ZDV, 3TC, d4T). All patients (mean CD4 cell count 448, range 297–777) had been on stable antiretroviral therapy for at least 2 months before they were included in the study, with HIV viraemia levels undetectable or constantly below 20 000 copies/ml.
Eight patients were under triple combination therapy for HIV infection (two reverse transcriptase inhibitors, including at least one pyrimidine analogue and one protease inhibitor), whereas four other patients were on double combination therapy (two reverse transcriptase inhibitors, including one pyrimidine analogue). These patients were treated with 6 MU IFN-α-2b one other day and ribavirin 800–1200 mg/daily for 6 months for chronic hepatitis C. Virological and immunological findings were examined at baseline and every 3 months, during 6 months of treatment. The HIV-RNA titre was measured by means of the nucleic acid sequence-based amplification system (NASBA; Organon Technica, Boxtel, the Netherlands) and HCV RNA was quantified by a quantitative polymerase chain reaction, Amplicor HCV (Roche Diagnostic Systems, NJ, USA).
Interestingly, mean HIV viraemia levels in these patients were decreased by 0.5 and 0.4 log10 at 3 and 6 months of therapy, respectively, compared with baseline values (Table 1). However, the decline in HIV viral load did not reach statistical significance (P > 0.05), as measured by Wilcoxon signed rank test. Furthermore, a comparison of mean HIV viraemia levels in patients treated with two pyrimidine analogues and patients treated with one pyrimidine analogue showed a reduction of 0.1 and 0.4 log10, respectively.
The HIV-RNA titre was thus not influenced by treatment with one or two nucleoside analogues that are potentially inhibited by ribavirin. In particular, three patients had undetectable HIV viral loads at baseline (the cut-off of the NASBA method is 80 copies/ml), which remained negative during the entire follow-up. Out of nine patients with detectable HIV-RNA levels at baseline, HIV viraemia levels, after 3 months of therapy, became negative in five patients, was found to be unchanged in two patients, decreased by 0.1 log10 in one patient and increased by 0.2 log10 in the final patient.
