Chronic Placental Inflammation Among Women Living With HIV in Uganda

Abstract

Background: HIV-exposed, uninfected (HEU) children have poorer early-life outcomes than HIV-unexposed children. The determinants of adverse health outcomes among HEU children are poorly understood but may result from chronic placental inflammation (CPI). Setting and methods: We enrolled 176 pregnant women living with HIV (WLWH) taking antiretroviral therapy in southwestern Uganda and 176 HIV-uninfected women to compare CPI prevalence by maternal HIV serostatus. Placentas were evaluated histologically by an expert pathologist for presence of CPI, defined as chronic chorioamnionitis, plasma cell deciduitis, villitis of unknown etiology, or chronic histiocytic intervillositis. Placentas with CPI were additionally, immunostained with CD3 (T cell), CD20 (B cell), and CD68 (macrophage) markers to characterize inflammatory cell profiles. Results: WLWH and HIV-uninfected women had similar age, parity, and gestational age. Among WLWH, the mean CD4 count was 480 cells/mL, and 74% had an undetectable HIV viral load. We detected CPI in 16 (9%) placentas from WLWH and 24 (14%) from HIV-uninfected women (P = 0.18). Among WLWH, CPI was not associated with the CD4 count or HIV viral load. Villitis of unknown etiology was twice as common among HIV-uninfected women than WLWH (10 vs. 5%, P = 0.04). Among placentas with CPI, more villous inflammatory cells stained for CD3 or CD68 among HIV uninfected women than WLWH (79% vs. 46%, P = 0.07). Conclusions: CPI prevalence did not differ by HIV serostatus. T-cell (CD3) and macrophage (CD68) markers were more prevalent in placental inflammatory cells from HIV-uninfected women. Our results do not support CPI as a leading mechanism for poor outcomes among HEU children in the antiretroviral therapy era.