One of the choice criteria for antiretroviral therapy, once the viral load is controlled, is long-term treatment safety. Safety, despite similarities in each therapeutic class, can differ significantly from one agent to another, according to their respective pharmacokinetic and pharmacodynamic properties. We reviewed data on two very well-known NNRTIs, efavirenz and nevirapine, in this context. The pharmacokinetic properties of both agents are presented along with their impact on residual viremia and viral reservoirs, as well as their clinical consequences. The implications for the penetration of these antiretroviral drugs in the CNS and in female and male genital tracts are also discussed. Pharmacogenetics could become an interesting tool. Finally, the availability of new NNRTIs has recently boosted this therapeutic class, even if their long-term properties remain to be assessed. The consideration of all this data stresses the importance of communication among clinicians, virologists, and pharmacologists before choosing a treatment.
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