Determinants of mother-to-infant human immunodeficiency virus 1 transmission before and after the introduction of zidovudine prophylaxis

Background: Randomized controlled trials have demonstrated that zidovudine therapy decreases the mother-to-infant transmission of human immunodeficiency virus 1 (HIV-1). Data from large observational studies may provide further important findings on the effectiveness at the population level of combined treatments in decreasing transmission. Objective: To evaluate time trends in prophylactic interventions and the determinants of transmission both before and after the introduction of antiretroviral prophylaxis, and in treated and untreated mother-infant pairs after 1995. Design and Setting: Analysis of prospective data on 3770 children born to HIV-1-infected women between 1985 and 1999 and reported to the Italian Register for HIV Infection in Children. Main Outcome Measures: Logistic regression random effects models were used to estimate crude and adjusted odds ratios for several factors potentially influencing vertical transmission for 2 periods-1985 through 1995 (Januaryl, 1985, through December 31, 1995) and 1996 through 1999 (January 1, 1996, through December 31, 1999), and between treated and untreated children after 1995. Results: The transmission rate was 15.5% in the 1985-1995 period and 5.8% in the 1996-1999 period. By 1999, prophylactic interventions had greatly increased. Antiretroviral treatment (ART) usage was 89.9%, (55.1% combination ART) and the elective cesarean delivery rate was 81.3%. In multivariate analysis, only elective cesarean delivery was associated with a lower risk of mother-to-infant transmission before 1995. After 1995, non', breastfeeding and receipt of ART were protective whereas elective cesarean delivery was not significantly protective in multivariate analysis. Transmission risk was reduced by 76% with an incomplete zidovudine regimen, 88% with a complete regimen, and 93% when the mother received combination ART. In the 1996-1999 period, the transmission rate for nonbreastfeeding mother-infant pairs was 8.6% with elective cesarean delivery, 4.4% with any ART, and 2.4% with these interventions combined. Conclusion: Prophylactic interventions, and in particular ART, reduced perinatal HIV-1 transmission at a population level in Italy.