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Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency virus transmission (HIV), but its consequences for disease progression among children infected despite Zdv exposure remain unknown. In a multicenter observational cohort study of 325 HIV-infected children born during 1986-1997, clinical progression was compared among infected children exposed or unexposed to Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8-fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS or death after adjusting for year of birth, maternal CD4 cell count, maternal AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10) viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No infected child treated early with multidrug therapy progressed to AIDS or died by 1 year, regardless of early Zdv exposure. More rapid disease progression was observed among infected children exposed during pregnancy or birth to Zdv if effective multidrug therapy was not initiated.

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.