Vertical transmission of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant

To confirm the vertical transmission of multidrug-resistant (MDR) human imm unodeficiency virus type 1 (HIV-1) and to assess its impact on further evol ution of drug-resistant virus in an infant, proviral DNA amplified from inf ected peripheral blood mononuclear cell cultures was sequenced to identify reverse transcriptase (RT) and protease (PR) mutations. The infant had prov iral DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR sub stitutions (K20R, M36I, and V82A). After delivery, the mother's proviral DN A had the same substitutions. Phylogenetic analyses of these HIV-1 RT and P R sequences indicated epidemiological linkage. Plasma drug susceptibility w as determined by using a recombinant virus assay. Plasma HIV-1 obtained aft er the infant's birth demonstrated reduced susceptibility to zidovudine and ritonavir. Thus, vertical transmission of MDR HIV-1 was demonstrated in th e setting of detectable maternal plasma viremia. Further accumulation of br oad MDR in the infant's virus to 3 antiretroviral classes occurred, despite postnatal therapy.