Zidovudine resistance phenotype and risk of perinatal HIV-1 transmission in zidovudine monotherapy-treated mothers with moderately advanced disease

The association of phenotypic zidovudine resistance with perinatal transmission was evaluated in 74 zidovudine-treated mothers enrolled in the Women and Infants Transmission Study through September 1994. Women in the sample had moderately advanced disease, with a median CD4(+) cell count of 271/muL and a median plasma HIV-1 RNA level of 39,811 copies/mL. Factors independently associated with zidovudine resistance at delivery (50% inhibitory concentration [IC50], >0.1 muM) in multiple logistic regression included prepregnancy zidovudine use, high log plasma HIV-1 RNA level, and low CD4(+) cell count. Of 74 mothers, 16 (22%) transmitted HIV-1 to their infants. After adjustment for duration of membrane rupture and CD8+ cell count, zidovudine resistance (IC50 range, 0.01-2.2 muM) was associated with an increased odds of transmission (ORadj, 1.25 per 0.1 muM; 95% confidence interval, 1.01-1.54), suggesting a decreased effect of prenatal zidovudine on preventing transmission in mothers infected with zidovudine-resistant virus. However, when the analysis was limited only to those mothers infected with virus containing zidovudine resistance mutations, no association between phenotypic resistance and transmission remained, indicating that phenotype may not provide significant additional information in predicting transmission where resistance genotype is known.