In the PROMISE (Promoting Maternal and Infant Survival Everywhere) trial, infants of women randomized to tenofovir, emtricitabine, lopinivir/ritonavir (TDF/FTC/LPV/r) had higher risk of very premature birth, very low birth weight, and death compared to those randomized to zidovudine, lamivudine, lopinavir/ritonavir (ZDV/3TC/LPV/r).
Data from two large prospective US-based cohort studies (the Surveillance Monitoring for ART Toxicities cohort and the International Maternal Pediatric Adolescent AIDS Clinical Trial Network P1025 study), were used to compare risk of adverse infant birth outcomes among women exposed to ZDV/3TC/LPV/r, TDF/FTC/LPV/r, and the more frequently used TDF/FTC with atazanavir and ritonavir (ATV/r). Exposure classification was based on first regimen used during pregnancy. We evaluated the risk of preterm birth (<37 weeks), very preterm birth (<34 weeks), low birth weight (<2,500 g), very low birth weight (<1,500 g), adverse event (preterm, low birth weight, fetal loss, or 14-day mortality) and serious adverse event (very preterm, very low birth weight, fetal loss, or 14-day mortality). Risk ratios (RR) with 95% confidence intervals (CI) were estimated using log binomial models. When number of outcomes was sufficient (preterm, low birth weight, adverse event), models were adjusted for confounding.
Among 4,646 enrolled infants, 128 (2.8%) had mothers who received TDF/FTC/LPV/r, 539 (11.6%) had mothers who received TDF/FTC/ATV/r, and 954 (20.5%) had mothers who received ZDV/3TC/LPV/r. The overall prevalence of adverse birth outcomes was 18.8% for preterm birth, 4.5% for very preterm birth, 17.3% for low birth weight, and 1.9% for very low birth weight. In crude and adjusted comparisons, there was no statistically significant difference between TDF/FTC/LPV/r and ZDV/3TC/LPV/r for any outcome (Table), although TDF/FTC/ATV/r appeared slightly protective for preterm birth, low birth weight, and any adverse event.
Among pregnant women with HIV in the US, use of TDF/FTC/LPV/r was not associated with increased risk of adverse infant birth outcomes when compared to ZDV/3TC/LPV/r or TDF/FTC/ATV/r. Our findings support the use of TDF/FTC/ATV/r during pregnancy, as it appears to carry similar or slightly less risk of preterm birth, low birth weight, and adverse events than ZDV/3TC/LPV/r.