HIV-1 drug-resistance and drug-dependence.

In this review, we will describe several recent HIV-1 studies in which a drug-dependent virus variant was selected. A common evolutionary route to the drug-dependence phenotype is proposed. First, the selection of a drug-resistance mutation that also affects the function of the targeted viral protein. Second, a compensatory mutation that repairs the protein function, but in the presence of the drug, which becomes an intrinsic part of the mechanism. The clinical relevance of drug-dependent HIV-1 variants is also discussed.