Molecular ZDV-resis tance and the risk of perinatal HIV-1 transmission in the women & infants transmission study

Objective: To assess the association of ZDV resistance with perinatal transmission. Methods: We sequenced the RT region of clinical isolates from 136 HIV-1 infected women enrolled in WITS who were treated with ZDV during pregnancy, and estimated the association of having ZDV associated HIV-1 RT mutations with transmission using retrospective cohort analysis. Results: 34% of these women had been on ZDV prior to pregnancy. At delivery, median CD4 cell count was 315 /μL and the median maternal plasma HIV-RNA level was 2.48 × 10 ⁴ copies/mL. Twenty-five percent (n=34) of maternal isolates had at least one ZDV-associated resistance mutation. Lower CD4 cell percent and count (p= 0.0001), and higher plasma HIV-1 RNA (p = 0.006) were associated with having ZDV resistance mutation at delivery. Multivariate logistic regression identified having any RT resistance mutation [OR: 5.45; 95% CI: 1.18,25.16; p =0.03], duration of ruptured membranes [OR 139 (1.05,1.84) per 10 hrs duration; p=0.02], and totallymphocyte count at delivery [OR: 1.06 (1.01,1.10) per 50 cells higher level; p = 0.009] as independently associated with transmission. In contrast, markers of maternal viral load and CD4 during pregnancy were not associated with perinatal transmission in the subset evaluated. Interpretation: Our results indicate that prevalence of molecular ZDV resistance among this subset of mothers who were on ZDV treatment because of clinical findings or low CD4 was moderately high. ZDV resistance was predictive of transmission, independent of viral load and CD4, in these mothers.