Ribavirin (RBV) does not alter intracellular levels of AZT, 3TC or d4T

In a late-breaker oral presentation, Gries and colleagues presented results from a PK sub-study of the APRICOT trial. This study randomised more than 800 patients coinfected with HIV and HCV to either standard interferon-alfa + ribavirin, pegylated interferon (Pegasys) + placebo or Pegasys + ribavirin. Results from the full APRICOT study are reported in detail later in this issue of HTB.

The PK study only included patients receiving pegylated interferon +/- ribavirin 800mg/day or placebo. Stable background HAART included either AZT+3TC or d4T+3TC for more than six weeks prior to the study.

Serial blood samples were collected at 0, 2, 4, 6, 8 and 12 hours at baseline and after 8-12 weeks of therapy. Plasma concentrations of RBV, d4T, AZT and 3TC were determined by LC/MS/MS and triphosphate metabolites in PBMCs by template primer extension assays.

No significant differences were found in either the mean plasma or intracellular AUC levels between baseline and week 8-12 in the 48/55 patients who completed the sub-study. The study concluded that coadministration of ribavirin does not alter the intracellular phosphorylation or the plasma pharmacokinetics of AZT, d4T or 3TC in coinfection patients after 8-12 weeks.

Comment

For historical reasons, the main concern at the time when this sub-study in APRICOT was designed was the inhibition of the phosphorylation of pyrimidine-analogues by ribavirin.

However, today the toxicity of ddI which may be increased by a promotion of phosporylation by ribavirin is of a much greater relevance. Unfortunately data on this interaction are not provided by this study.

Gries J-M, Torriani FJ, Rodriguez-Torres M et al. Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with HCV/HIV co-infection: final results of a randomised clinical study. 11th CROI 2004, Abstract 135LB.