Antiretroviral resistance in viral isolates from HIV-1-transmitting mothers and their infants

Abstract

To characterize concordance of resistance mutations to antiretroviral drugs (ART) in mother-infant pairs. Case series of HIV-transmitting mothers and infants in the Women and Infants Transmission Study, where delivery occurred between April 1994 and December 1999. Reverse transcriptase and protease genes were sequenced in stored viral isolates from 32 mother-infant pairs. Mutations were coded as "pure mutants" where only mutant virus was detected or as "mixtures" where a mixed mutant/wild-type population was identified. ART resistance mutations were compared for concordance between mothers and their infants. Maternal mutations associated with resistance to nucleoside reverse transcriptase inhibitor (NRTI) and minor protease inhibitor (PI) drugs were typically concordant with that of infant, while those associated with non-nucleoside reverse transcriptase inhibitors (NNRTI) and major PI drugs were not. Of five NRTI-associated maternal mutations observed, three pure mutants corresponded with mutant in the infant, while two wild-type-predominant mixtures corresponded with infant wild type. The only NNRTI-associated mutation observed, K103N, was not transmitted, nor were the two major PI-associated mutations, L90M and V82I/V. Transmission of minor PI-associated mutations was consistent with the sole observed or dominant variant for 20 of 21 mutations. For NRTI- and minor PI-associated mutations, transmission was consistent with relative quantity of variants in maternal virus. However, where NNRTI- and major PI-associated mutations were present in three cases, they were not transmitted, even where only mutant virus was detectable in maternal isolates. This is consistent with evidence of loss of transmission with resistance to NNRTI and PI drugs.