HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.
Bottom Line: In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight.Progesterone supplementation resulted in a significant improvement in fetal weight.In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.
Affiliation: Toronto General Research Institute, University Health Network.Show MeSH
Related in: MedlinePlus
Mentions: We first investigated the impact of HIV antiretrovirals on progesterone levels in vitro, using BeWo cells, a third-trimester human cytotrophoblast cell line capable of sex steroid production . Antiretrovirals were tested singly and in clinically relevant combinations, at 10 times the MEC for 24 hours. These conditions did not result in cytotoxicity or inhibition of proliferation. Of the 3 different classes of drugs tested—NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), and PIs—only PIs resulted in reduced progesterone levels (Figure 1A). RTV, known for its significant impact on CYP enzymes , had the strongest inhibitory effect on progesterone levels. ATV and LPV also decreased progesterone levels, while darunavir (DRV) was the only PI tested that did not significantly affect progesterone release. Nevirapine, ZDV, and 3TC had no effect on progesterone levels.Figure 1.
Affiliation: Toronto General Research Institute, University Health Network.