Birth and clinical outcomes of pregnant participants with advanced HIV disease

Introduction: Clinical trials for the evaluation of novel diagnostics and treatments for HIV-associated opportunistic infections have historically excluded pregnant persons. Little information is available regarding the clinical outcomes and pregnancy outcomes of pregnant persons with advanced HIV disease while taking opportunistic infection prophylaxis for tuberculosis (TB) and cryptococcosis. In this study, we describe characteristics at enrollment, clinical outcomes, and birth outcomes of pregnant people with advanced HIV in Uganda. Methods: We prospectively enrolled pregnant adults with advanced HIV disease within an on-going pragmatic cluster randomized clinical trial evaluating an enhanced screening and prophylaxis package for opportunistic infections (NCT05085171). The trial began enrollment in May 2022 and continues in 26 outpatient HIV clinics in the Kampala and Wakiso districts of Uganda. We present an analysis of pregnant participants enrolled through April 30, 2025, including their characteristics at study enrollment, opportunistic infections, and birth outcomes. Results: Overall, 15% (114/766) of female participants with advanced HIV disease were pregnant. Median CD4 cell count was 124 cells/µL (IQR: 82-170). Median time since HIV diagnosis was 7 days, and 45% were ART-naive at enrollment. Compared with non-pregnant female participants, pregnant participants were less likely to have a positive cryptococcal antigen (CrAg) test (2% vs 7%, p=0.023), to have a positive Alere tuberculosis (TB) lipoarabinomannan (LAM) test (11% vs 28%, p<0.001), and to be receiving active TB treatment (14% vs 39%, p<0.001). Overall, 18% (21/114) experienced at least one opportunistic infection during the study, of which 71% (n=15) were attributed to TB. Eighty-six percent (98/114) of pregnancies were carried to term. Participants on TB preventive therapy (TPT) had 94% of deliveries at term (51/54), compared with 80% (36/45) among participants who did not receive TPT (OR = 4.25, 95%CI:1.07-16.80), and 67% (8/12) among participants on active TB treatment (OR = 8.50, 95%CI: 1.60-45.25). Conclusions: Although the incidence of opportunistic infections is less commonly reported among pregnant women with advanced HIV disease, TB is the most frequent opportunistic infection. Participants on TPT had 4-fold higher odds of having a term delivery compared with those not on TPT and 8-fold higher odds compared with those with active TB.