Effects of individual drug and combination antiretroviral therapy on trophoblast proliferation

Abstract

BackgroundCombination antiretroviral therapy (cART) has been reported to reduce perinatal transmission of human immunodeficiency virus (HIV) and improve maternal survival outcomes. Recent studies have associated in-utero exposure to cART drugs with adverse outcomes such as pre-eclampsia, preterm delivery, low birth weight and small-for-gestational-age births. However, the exact molecular mechanisms underlying cART-induced adverse pregnancy outcomes remain poorly defined. ObjectivesTo investigate the effects of cART drugs on trophoblast proliferation in the HTR-8/SVneo cell line. Study designHTR-8/SVneo cells were exposed to tenofovir (0.983–9.83 µM), emtricitabine (0.809–8.09 µM) and efavirenz (0.19–1.09 µM), the individual drugs of the first-line single tablet cART regimen termed ‘Atripla’, and zidovudine (1.12–1.12 µM), lamivudine (0.65–6.5 µM), lopinavir (0.32–3.2 µM) and ritonavir (0.69–6.9 µM), the individual drugs of the second-line single tablet cART regimen termed ‘Aluvia’. The cells were treated for 24, 48, 72 and 96 h, and trophoblast proliferation was assessed using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltretrazolium bromide assay. ResultsTwo-way analysis of variance showed a significant dose-dependent decrease (p < 0.05) in trophoblast proliferation in response to individual and combined drug components of first- and second-line antiretroviral therapy. ConclusionsFirst- and second-line cART drugs inhibit trophoblast proliferation, and may contribute to placenta-mediated adverse pregnancy outcomes in patients with HIV.