Protease Inhibitor–Based Antiretroviral Therapy and Fetal Growth Restriction

Anna Wald, MD, MPH reviewing Papp E et al. J Infect Dis 2015 Jan 1. Powis KM and Shapiro RL. J Infect Dis 2015 Jan 1

Mechanistic studies provide support that the association is mediated by low progesterone.

The success of antiretroviral (ARV) therapy for preventing maternal-to-child HIV transmission has been tempered by excess risk for preterm birth, especially among pregnant women who receive protease inhibitors (PIs). Various data have suggested that low progesterone may play a role. To further investigate this mechanism, investigators conducted a series of experiments in cell lines and mice and an observational study in 44 pregnant women with or without HIV infection.

When trophoblastic progesterone-producing cells were exposed to ARVs, protease inhibitors (except darunavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or non-NRTIs resulted in diminished progesterone release. Pregnant mice treated with PI-containing ARV combinations had higher incidence of fetal resorption, lower fetal and placental weights, and lower progesterone levels than mice treated with NRTIs. Treatment with supplemental progesterone alleviated the reduction in fetal weight. Pregnant HIV-infected women who received PIs had substantially lower third-trimester progesterone levels than HIV-negative women. In both pregnant women and mice, progesterone levels correlated with birth weight.

Citation(s):

Papp E et al. HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction. J Infect Dis 2015 Jan 1; 211:10.

Powis KM and Shapiro RL.Protease inhibitors and adverse birth outcomes: Is progesterone the missing piece to the puzzle? J Infect Dis 2015 Jan 1; 211:4.