Effects of individual drug and combination antiretroviral therapy on trophoblast proliferation

Sanelisiwe Nzuza; Silindile I Hadebe; Arieh A Katz; Mushi Matjila

doi:10.1016/j.ejogrb.2024.04.035

Effects of individual drug and combination antiretroviral therapy on trophoblast proliferation

Eur J Obstet Gynecol Reprod Biol. 2024 Apr 27:298:66-73. doi: 10.1016/j.ejogrb.2024.04.035. Online ahead of print.

Authors

Sanelisiwe Nzuza¹, Silindile I Hadebe², Arieh A Katz³, Mushi Matjila⁴

Affiliations

¹ Nelson Mandela University, Faculty of Health Sciences, Department of Pharmacy, Port Elizabeth, South Africa. Electronic address: sanelisiwe.nzuza@mandela.ac.za.
² Nelson Mandela University, Faculty of Health Sciences, Department of Pharmacy, Port Elizabeth, South Africa.
³ Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, SAMRC/UCT Gynaecological Cancer Research Centre, University of Cape Town, Cape Town, South Africa.
⁴ Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, SAMRC/UCT Gynaecological Cancer Research Centre, University of Cape Town, Cape Town, South Africa; Department of Obstetrics and Gynaecology, Groote Schuur Hospital, Cape Town, South Africa.

PMID: 38733775
DOI: 10.1016/j.ejogrb.2024.04.035

Abstract

Background: 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.

Objectives: To investigate the effects of cART drugs on trophoblast proliferation in the HTR-8/SVneo cell line.

Study design: HTR-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.

Results: 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.

Conclusions: First- and second-line cART drugs inhibit trophoblast proliferation, and may contribute to placenta-mediated adverse pregnancy outcomes in patients with HIV.

Keywords: Cell proliferation; Combination antiretroviral therapy; Extravillous trophoblast; HIV; Mother-to-child transmission.