February 5, 2001
Session 29 focused on the pharmacology of antiretroviral drugs. T.L. Parsons presented data looking at whether prior treatment with the thymidine analogues (either d4T or ZDV) impairs the intracellular phosphorylation of d4T, ZDV, or abacavir using an ex vivo assay system. This subject has been the subject of much debate ever since Sommadossi presented data (at the 5th CROI 1998) suggesting the prior use of ZDV somehow inhibited the phosphorylation of d4T (the active drug within cells). The issue bears on the debate about sequencing NRTIs (specifically the thymidine analogues ZDV and d4T). Numerous clinical studies have failed to support the observation of Sommadossi. The ex vivo system utilized by Parsons et al. used samples from five groups of ten patients (ten treatment-naive, ten on d4T suppressed, ten on d4T with some difficulties, ten on ZDV suppressed, and ten on ZDV with problems). The result was that the sequence of thymidine analog did not significantly impact ex vivo phosphorylation levels refuting the Sommadossi hypothesis. No significant effect on abacavir (actually the active drug = carbovir) phosphorylation was seen with prior d4T or ZDV pretreatment.
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