McDonald CR, et al. - A secondary retrospective analysis was performed of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)–infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)–based or efavirenz (EFV)–based combination antiretroviral therapy (cART). Researchers recognized that in pregnancy, combination ART regimens differentially affect estradiol levels, a hormone critical to the maintenance of a healthy pregnancy. Thereby highlighting the urgent necessity for identifying cART regimens that minimize perinatal HIV transmission without contributing to hormonal dysregulation.

Methods

• Researchers enrolled 326 women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy.
• They used enrollment samples collected prior to cART initiation as a cART-naive comparator group.
• Enzyme-linked immunosorbent assay was used to quantify hormone levels.

Results

• The 2 cART regimens differentially affected estradiol levels.
• Relative to the cART-naive gestationally matched comparator group, exposure to LPV/r was associated with an increase in estradiol (P < .0001), whereas exposure to EFV was associated with a decrease in estradiol (P < .0001).
• Researchers observed that lower estradiol levels had correlation with small for gestational age (SGA) (P=.0019) and low birth weight (P=.019) in the EFV arm, while higher estradiol levels had correlation with SGA in the LPV/r arm (P=.027).
• Although treatment arms were similar regarding progesterone levels, an association between SGA and lower progesterone was observed in the LPV/r arm (P=.04).
• They identified no association between hormone levels and preterm birth in either arm.
• In cases of stillbirth, levels of progesterone and estradiol were lower
• In 5 of 8 cases, levels of both hormones declined immediately prior to stillbirth.