Should Nucleoside Reverse Transcriptase Inhibitors be Discontinued when Ribavirin is used?

The nucleoside reverse transcriptase inhibitors are taken up into host cells and are then triphosphorylated into active agents by cellular kinases. AZT (zidovudine) and d4T (stavudine) are analogues of thymidine and ddC (dideoxycytidine) and 3TC (lamivudine) are analogues of cytidine. Ribavirin is a guanosine analogue that also requires phosphorylation to an active form by cellular kinases.

It has been shown in vitro that ribavirin can competitively inhibit the thymidine kinase required for the phosphorylation of AZT and possibly other agents in this class.96,97 Ribavirin in vitro can also inhibit the metabolism of DDI resulting in increased concentrations of this agent and theoretical potentiation of the antiviral activity. The clinical relevance of these in vitro observations remains uncertain, but no significant variation in HIV replication was observed in a recent study of "combination therapy" in a co-infected population 98. Recommendation: There are insufficient clinical ... more.

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