Abstract
Combination 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. To investigate the effects of cART drugs on trophoblast proliferation in the HTR-8/SVneo cell line. HTR-8/SVneo cells were exposed to tenofovir (0.983-9.83µM), emtricitabine (0.809-8.09µM) and efavirenz (0.19-1.09µM), the individual drugs of the first-line single tablet cART regimen termed 'Atripla', and zidovudine (1.12-1.12µM), lamivudine (0.65-6.5µM), lopinavir (0.32-3.2µM) and ritonavir (0.69-6.9µM), the individual drugs of the second-line single tablet cART regimen termed 'Aluvia'. The cells were treated for 24, 48, 72 and 96h, and trophoblast proliferation was assessed using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltretrazolium bromide assay. Two-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. First- and second-line cART drugs inhibit trophoblast proliferation, and may contribute to placenta-mediated adverse pregnancy outcomes in patients with HIV.
Published Version
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