Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone

Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Sevilla, Spain.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.31). 10/2008; 62(6):1365-73. DOI: 10.1093/jac/dkn420
Source: PubMed


To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine.
A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared.
In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day.
HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.

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    • "Successful treatment of chronic hepatitis C infection with pegylated interferon and ribavirin combination therapy has been shown to stop progression of fibrosis and prevent liver related disease and death [5], but treatment of HCV in HIV coinfected individuals is complicated by additive drug toxicities of ribavirin and the nucleoside reverse transcriptase inhibitors didanosine [6,7], zidovudine [8-11] and stavudine [12]. Furthermore, competitive intracellular phosphorylation of abacavir and ribavirin has recently been hypothesized to further compromise the efficacy of HCV treatment in the coinfected host [13-15], although this is absent using weight based doses of ribavirin [14-16]. "
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