Probability of vertical HIV transmission: A systematic review and meta-regression.

Abstract

Background: Eliminating HIV vertical transmission (VT) is a global priority and monitored by estimating paediatric HIV infections with the Joint United Nations Programme on HIV/AIDS supported Spectrum AIDS Impact Module (Spectrum-AIM). Recent innovations in antiretroviral therapy (ART) service delivery models and first-line regimens aimed to reduce VT probabilities. We conducted a systematic review and meta-analysis to estimate VT probabilities by maternal immunologic and treatment status.

Methods: We combined an updated systematic review with previous data in meta-regression models to estimate VT probabilities and determinants. We searched multiple databases for peer-reviewed English-language studies from all regions published between January 2018 and February 2024 with VT data stratified by maternal immunologic or treatment status from randomized trials, cohort, or observational studies. Four meta-regression models estimated VT probabilities. We assessed model sensitivity and compared estimates to Spectrum-AIM's previous results. Finally, we fit a meta-regression model to assess the association of ART class and initiation timing on viral load suppression (VLS) at delivery.

Findings: The updated review identified 24 new studies, yielding 110 total studies included in meta-regression analysis. For women not receiving ART, higher CD4 was associated with lower odds of perinatal VT (odds ratio [OR] 0.80 (95% CI: 0.75-0.84) per 100 CD4 cells/μL increase). For pregnant women on ART, each additional week on ART before delivery reduced odds of VT by 5.6% (3.2%-7.0%). The odds ratio of perinatal VT among pregnant women initiating integrase inhibitor-based ART 20 weeks pre-delivery was 0.36 (0.14-0.94) compared to those initiating non-nucleoside reverse transcriptase inhibitors (NNRTI)-based ART. This association was confounded by study region. Odds of VLS were lower when ART was initiated late in pregnancy (OR: 0.37 (0.21-0.68) for the reference regimen (NNRTI)), without significant difference by ART regimen.

Interpretation: VT probability varies by maternal immunologic stage, treatment regimen, and timing of treatment initiation. These estimates have been incorporated into Spectrum-AIM for UNAIDS 2025 HIV estimates. Earlier ART initiation is associated with higher odds of VLS at delivery. Further evidence is needed on the effects of recent ART innovations on VT outcomes.

Funding: NIH, UNAIDS, and UKRI.