SELECTIVE VERTICAL TRANSMISSION OF HIV-1 ANTIRETROVIRAL RESISTANCE MUTATIONS

Objective: To examine the patterns of vertical transmission of zidovud ine (ZDV) resistance mutations. Design: HIV-1 reverse transcriptase co dons 10-250 were sequenced from 24 pairs of ZDV-exposed women and thei r HIV-infected infants as part of the Women and Infants Transmission S tudy. Methods: Viral RNA was extracted from tissue culture supernatant s and sequenced using fluorescent dye-primer chemistry and an automate d sequencer. Results: For 17 of these pairs, maternal and infant seque nces were identical to one another and lacking known ZDV resistance mu tations. The remaining seven maternal sequences contained known mutati ons associated with ZDV resistance at reverse transcriptase codons 70, 210, 215 and 219. In each case where the maternal HIV isolate showed a pure mutant species, the infant sequence was identical. When the mat ernal sequence showed the presence of a sequence mixture at codon 70 o r 219, the infant's virus showed only wild-type sequence even when the ZDV-resistant mutant was quantitatively dominant in the mother. The s ingle maternal HIV isolate showing mixed sequence at codon positions 2 10 and 215 transmitted an unmixed mutant to the infant at both positio ns. When maternal mixtures were present at sites not associated with Z DV resistance, only the dominant species appeared in the infant. Concl usions: When maternal HIV isolates contained mixed wild-type and ZDV-r esistant subpopulations, only a single component of the mixture could be detected in the infected infants. Resistance mutants without the co don 215 mutation were not transmitted from mixtures, even when the mut ants formed the majority of circulating maternal virus. In perinatal H IV transmission, specific ZDV-resistant HIV genotypes circulating in t he maternal virus pool may influence whether infection in the infant w ill be established by a wild-type or ZDV-resistant HIV strain. (C) 199 8 Lippincott Williams & Wilkins.