HIV-1 genotypic zidovudine drug resistance and the risk of maternal-infanttransmission in the Women and Infants Transmission Study

Objectives: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased amo ng women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistanc e in perinatal transmission was evaluated. Methods: The reverse transcriptase (RT) region of clinical isolates from cu lture supernatants of 142 HIV-1-infected women enrolled in the Women and In fants Transmission Study (WITS), who had been treated with ZDV during pregn ancy was sequenced. Results from genotypic sequencing were linked to demogr aphic, laboratory, and obstetrical databases, and the magnitude of associat ion of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. Results: Twenty-five per cent (34/142) of maternal isolates had at least on e ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P = 0.0001) and higher plasma HIV-1 RNA (P = 0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mu tation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P = 0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h d uration; P = 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 5 0 cells higher revel; P = 0.009] were independently associated with transmi ssion in multivariate analysis.