Antenatal antiretroviral therapy (ART) reduces rates of early HIV transmission compared with zidovudine alone but results in an increased risk of adverse maternal and neonatal outcomes, according to a study published in the New England Journal of Medicine.

Mary G. Fowler, MD, MPH, from the Department of Pathology at the Johns Hopkins University School of Medicine in Baltimore, and colleagues conducted the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial to compare the efficacy and safety of various antiretroviral therapy strategies for the prevention of mother-to-child transmission during pregnancy among HIV-infected women with high CD4 counts.

The study included 3590 HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter (median CD4 count 530 cells per cubic millimeter). The primary outcomes of the trial were HIV transmission in the infant at 1 week of age and maternal and infant safety. Adverse events were graded on the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events.

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The participants were randomly assigned to receive either zidovudine and single-dose nevirapine in addition to a 1-to-2 week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone), zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART), or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART).

The rate of HIV transmission was significantly lower in the combined ART groups compared with zidovudine alone (0.5% vs 1.8%). However, the rate of maternal grade 2 to grade 4 adverse events was higher among participants receiving zidovudine-based ART compared with zidovudine alone (21.1% vs 17.3%) and the rate of grade 2 to grade 4 abnormal blood chemical values was higher in the tenofovir-based ART (2.9% vs 0.8%).

The researchers note that the rate of adverse events did not differ significantly between the ART groups. They also observed a higher rate of infants born with a birth weight of less than 2500 g in the zidovudine-based ART group compared with zidovudine alone (23.0% vs 12.0%) and in the tenofovir-based ART group compared with zidovudine alone (16.9% vs 8.9%).

Preterm delivery before 37 weeks was more common in the zidovudine-based ART group compared with zidovudine alone (20.5% vs 13.1%). Tenofovir-based ART was associated with increased rates of preterm birth before 34 weeks compared with zidovudine-based ART (6.0% vs 2.6%) as well as early infant death (4.4% vs 0.6%).

“On the basis of recent trials, the WHO [World Health Organization] recommends ART for HIV-infected persons regardless of CD4 cell count, and there are clear benefits of ART for the prevention of mother-to-child transmission and maternal health,” the study authors noted.

“However, it is also clear that the most efficacious and safest triple-drug ART regimens during pregnancy remain to be defined. Our findings emphasize the need for continued research to assess ART in pregnancy to ensure safer pregnancies for HIV-infected women and healthier outcomes for their uninfected infants.”


  1. Fowler MG, Qin M, Fiscus SA, et al. Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med. 2016;375:1726-1736. doi: 10.1056/NEJMoa1511691.