711   Phenotypic Zidovudine (ZDV) Resistance and Perinatal HIV-1 Transmission.

G. Bauer*¹, J. Pitt^2,3, R. Colgrove⁴, and S. Welles¹for the WITS Study Team.
¹Univ. of Minnesota, Minneapolis;²Columbia Univ., New York, NY;³Women and Infants Transmission Study (WITS); and⁴Harvard Med. Sch., Boston, MA.

Background:We previously had linked perinatal HIV-1 transmission with ZDV drug resistance RT mutations among HIV-1-infected women enrolled in the WITS through March 1994. However, ZDV phenotypic resistance had not been evaluated for its association with perinatal transmission in this group of women with moderately advanced disease (mean CD4 cell count = 289), many of whom (32%) had received ZDV for their own infection prior to pregnancy.

Methods:All mothers previously shown to have ZDV resistance mutations (n = 36 with mutations at RT codons 41, 67, 70, 210, 215 and 219) and 45 mothers with wild-type (WT) virus were selected for ZDV susceptibility analysis by the ACTG/DoD assay. Results were linked to maternal factors and infant infection status to produce complete data on 56 mothers. Logistic regression was used to estimate the association of ZDV phenotypic resistance with transmission.

Results:Factors associated with maternal ZDV resistance at delivery included ZDV use prior to pregnancy [adjusted OR = 3.86 (0.81, 18.33)], log plasma HIV RNA [adj. OR = 2.02 (1.10, 3.70) per 1 log] and log CD4 % [adj. OR = 0.10 (0.10, 1.01) per 1 log] at delivery. 11 of 56 (20%) mothers transmitted HIV-1 to their infants. 6 of 11 (55%) transmitting mothers had ZDV resistance (>0.1mM IC₅₀) compared to 16 of 45 nontransmitters (36%). While after adjustment for duration of membrane rupture and maternal total lymphocyte count at delivery (both associated with transmission in univariate analysis) there was a trend towards increased transmission among mothers having ZDV phenotypic resistance [adj. OR = 5.80 (0.98,34.31)], when ZDV susceptibility was considered as a continuous variable (IC₅₀, range 0.01—2.2mM) it was significantly associated with increased transmission [adj. OR = 1.21 (1.05, 1.40) per 0.1mM IC₅₀].

Conclusions:ZDV phenotypic resistance was associated with mother-infant transmission independent of viral load in this group of ZDV-treated women with moderately advanced disease.