The molecular epidemiology of HIV-1 envelope diversity during HIV-1 subtype C vertical transmission in Malawian mother–infant pairs

Abstract

To study the relationship between HIV-1 subtype C genetic diversity and mother-to-child transmission and to determine if transmission of HIV-1 V1/V2 env variants occurs stochastically. Case-case-control study of Malawian mother-infant pairs consisting of 32 nontransmitting women, 25 intrauterine transmitters, and 23 intrapartum transmitters in Blantyre, Malawi. A heteroduplex tracking assay against the highly variable HIV-1 env V1/V2 region was used to characterize the relationship between HIV-1 diversity and mother-to-child transmission. The relative abundance of the maternal env variants was quantified and categorized as transmitted or nontransmitted based on the env variants detected in the infant plasma. The V1/V2 region was sequenced from two mother-infant pairs and a phylogenetic tree was built. No relationship was found between transmission and overall maternal env diversity. Infants had less diverse HIV-1 populations than their mothers, and intrauterine-infected infants had fewer V1/V2 variants and were more likely to harbor a homogeneous V1/V2 population than infants infected intrapartum. V1/V2 sequences cloned from two mother-infant transmission pairs support multiple env variant transmission when multiple variants are detected, rather than single variant transmission followed by diversification. Almost 50% of the HIV-infected infants contained V1/V2 env variants that were not detected in maternal plasma samples. Finally transmission of env variants was not related to their abundance in maternal blood. These data suggest that the predominant mechanism(s) of HIV-1 subtype C mother-to-child transmission differs by the timing of transmission and is unlikely to be explained by a simple stochastic model.