In conclusion, these analyses demonstrate that, even after adjustment for a number of well-established clinical, demographic, and obstetrical risk factors, maternal PI-based ART regimens given for PMTCT among HIV-infected pregnant women remained an important risk factor for PTD/VPTD and LBW/VLBW outcomes, compared with antenatal ZDV alone. Moreover, TDF-based ART was significantly associated with greater numbers of severe adverse pregnancy outcomes than was ZDV-based ART. With the current rollout of lifetime ART according to "test and treat" recommendations by WHO and being implemented by the Ministries of Health, these results, which corroborate potential negative effects of maternal ART on pregnancy outcomes, need to be considered in the management of HIV-positive pregnant women so as to reduce the risk of LBW and PTD outcomes, as well as composite adverse pregnancy outcomes, that are associated with high rates of infant morbidity and mortality, particularly in resource limited settings. Further research is needed to elucidate the biologic mechanisms underlying these adverse pregnancy outcomes, to optimize maternal treatment/PMTCT regimens. In addition, more studies are required to investigate whether this effect occurs with other PI's or more recent ARV's such as some integrase inhibitors.
The authors gratefully acknowledge the contributions of all the mothers and their children who participated in the PROMISE trial.
The authors also gratefully acknowledge the site staff in PROMISE who conducted the trial; the FHI360 staff and the statistical staff at SDAC, Harvard School of Public Health; and the FSTRF Data Management Center; and the IMPAACT Leadership for their sustained support for the PROMISE study.
Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional investigator support was also provided by NIAID (K24 AI120796). The study products for the PROMISE 1077BF/1077FF trial were provided free of charge by Abbott/Abbvie, Gilead Sciences, Boehringer Ingelheim, and GlaxoSmithKline/Viiv with the exception of some nevirapine that was purchased at a discounted rate by a contractor to the Eunice Kennedy Shriver National Institute of Child Health and Human development for use in the trial. None of the pharmaceutical companies had any role in the trial design, data collection, data analysis, or manuscript writing.
J Acquir Immune Defic Syndr. 2019;81(5):521-532. © 2019 Lippincott Williams & Wilkins