Selection of drug-resistant variants in the female genital tract of human immunodeficiency virus type 1-infected women receiving antiretroviral therapy

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA , and antiretroviral drug-resistant variants in cervicovaginal secretions o f HIV-l-infected women receiving antiretroviral therapy, The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the num ber of antiretroviral drugs taken by the patients. Proviral DNA was detecte d in approximately half of all samples of cervicovaginal secretions from HI V-l-infected women, regardless of the presence or absence of HIV-1 RNA in c ervicovaginal secretions and of the antiretroviral regimen. In cervicovagin al secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against prote ase and reverse-transcriptase pol genes were found. Our observations indica te that antiretroviral therapy is not effective in purging the female genit al tract of cell-associated provirus and that antiretroviral drugs that pen etrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.