A Risk-Benefit Assessment of Zidovudine in the Prevention of Perinatal HIV Transmission

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Abstract
Mother-to-child transmission is the main mode of acquisition of HIV infection for children, and the estimated rate of vertical transmission ranges from 15 to 20% in Europe, 15 to 25% in the US and 25 to 35% in Africa. Vertical transmission is associated with clinical and immunological progression of disease in the mother, breastfeeding and possibly with vaginal delivery. Recently, the findings of the American/French AIDS Clinical Trial Group (ACTG) trial 076 showed that in women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, zidovudine (ZDV, 3′-azido-3′-deoxythymidine, AZT) reduced the risk of vertical transmission when administered during pregnancy and delivery and to the infant in the first 6 weeks of life. No significant adverse effects were observed in either the mothers or neonates. Although the results of the American/French trial on the use of zidovudine to prevent vertical transmission are encouraging, many questions remain unanswered. The optimal timing of administration of zidovudine is unknown, as is its effectiveness in women with clinical characteristics that differ from those of the women in the trial. Concern has been expressed about the possibility of long term effects of exposure of zidovudine during pregnancy, both for the mother and the infant (of whom 4 out of 5 are uninfected anyway) and the implications for antenatal screening. Further trials with different zidovudine regimens and other strategies to prevent vertical transmission are being planned in several countries.