Investigating how maternal HIV-1 infection and use of antiretroviral therapy impacts preterm birth using an in vitro model system

Andrews, Cameron

Investigating how maternal HIV-1 infection and use of antiretroviral therapy impacts preterm birth using an in vitro model system

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Department of Integrative Biomedical Sciences (IBMS)

Faculty

Faculty of Health Sciences

Abstract

Preterm birth (PTB) remains a leading cause of neonatal morbidity and mortality, yet the mechanisms linking diverse maternal factors to premature labour are poorly understood. Women living with HIV, as well as those receiving antiretroviral therapy, have an elevated risk of preterm birth, but the underlying pathways remain unclear. This study investigated the effects of HIV pseudovirions (HIV-PSV), antiretroviral drugs, and immune cell interactions on human myometrial contractility using an in vitro model. HIV-PSV Env induced significant myometrial contraction, while ARVs had no effect. Viral entry assays confirmed that contraction occurs independently of productive infection. HIV-PSV exposure reduced ERK1/2 phosphorylation but triggered secretion of IL-1β, IL-6, IL-8, and MCP-1, with IL-1β and IL-6 directly promoting contraction. These findings support a model in which Env-dependent signalling activates myometrial cells and drives autocrine, cytokine-mediated contraction. This mechanism provides a biologically plausible explanation for PTB risk in women living with HIV and identifies potential targets for therapeutic intervention to mitigate HIV-associated preterm labour.

Keywords

preterm birth

HIV

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