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 2periods-1985 through 1995 (January 1, 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 19851995 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, nonbreastfeeding 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.