Background: Whether ribavirin interferes with the pharmacokinetics of antiretroviral drugs is an important, but unanswered question relevant to the treatment of HCV in HIV-infected persons. Our objective was to examine the effect of RBV on intracellular phosphorylation of zidovudine (ZDV), lamivudine (3TC), and/or stavudine (d4T), and to determine whether plasma levels of RBV or these NRTIs are altered by co-administration.

Methods: This prospective nested pharmacokinetics study was incorporated into the design of the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT), a randomized, controlled, multinational trial in 868 patients with HCV/HIV co-infection. Eligible HCV/HIV-co-infected patients were receiving a highly active antiretroviral therapy (HAART) regimen that included stable doses of ZDV plus 3TC, or d4T plus 3TC for at least 6 weeks prior to enrollment. Eligible patients were randomized to treatment with peginterferon-α-2a (40KD) (PEGASYS) 180 μg/wk plus either oral RBV (COPEGUS) 800 mg/day or placebo; those randomized to interferon/RBV were excluded. Serial blood samples were collected predose (0) and 2, 4, 6, 8, and 12 hours after the morning dose of ZDV, 3TC, and/or d4T, at baseline (pretreatment) and after 8  to12 weeks of combination therapy. Concentrations of RBV, ZDV, 3TC, and d4T were determined in plasma by LC/MS/MS and the triphosphate anabolites of ZDV, 3TC, and d4T in peripheral blood mononuclear cells (PMBC) by template primer extension assays. Endogenous nucleotides (dTTP and dCTP) were also determined by primer extension assays. The area under the concentration-time curve (AUC_0-12h) was calculated and analyzed by ANCOVA.

Results: Of 55 patients, 48 completed the study, with the following results:

Conclusions: RBV (800 mg/day) does not alter the intracellular phosphorylation or plasma pharmacokinetics of ZDV, 3TC, or d4T in HCV/HIV-co-infected patients when assessed after 8 to 12 weeks of combination therapy.

Keywords: Pharmacokinetics; NRTI; Ribavirin