Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe

Objective To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women. Design Combined analysis of data from three observational studies. Setting USA and Europe. Population A total of 19 585 singleton infants born to HIV-infected women, 1990-2006. Methods Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study. Main outcome measure Preterm delivery rate (< 37 weeks of gestation). Results Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49-3.86) and NSHPC (AOR 1.43, 95% CI 1.10-1.86), but not in the PSD (AOR 0.92, 95% CI 0.67-1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19-1.87, P = 0.001), after adjusting for covariates. Conclusions Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART.