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

BACKGROUND: Eliminating HIV vertical transmission is a global priority and monitored by estimating paediatric HIV infections with the UNAIDS-supported Spectrum AIDS Impact Module (Spectrum-AIM). Recent innovations in antiretroviral therapy (ART) service-delivery models and first-line regimens aimed to reduce vertical transmission probabilities. We did a systematic review and meta-analysis to estimate vertical transmission probabilities by maternal immunological and treatment status. METHODS: In this systematic review and meta-regression, we combined an updated systematic review with previous data in meta-regression models to estimate vertical transmission probabilities and determinants. We searched PubMed, Embase, the Global Health Database, WHO Global Index Medicus, CINAHL Complete, and Cochrane CENTRAL for peer-reviewed English-language studies from all regions published between Jan 1, 2018 and Feb 8, 2024, with search term domains mentioning "HIV", "transmission", "perinatal", and "breastfeeding periods", and "infants born to women living with HIV" or related terms from randomised trials, cohort studies, or observational studies. Four meta-regression models estimated vertical transmission 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: Of 12 588 potential studies, we identified 24 new studies, which along with the 86 from previous reviews yielded 110 total studies included in meta-regression analysis. For women not receiving ART, higher CD4 count was associated with lower odds of perinatal vertical transmission (odds ratio OR 0·80, 95% CI 0·75-0·84, per 100 cells per μL increase). For pregnant women on ART, each additional week on ART before delivery reduced odds of vertical transmission by 5·6% (95% CI 4·2-7·0). The OR of perinatal vertical transmission among pregnant women initiating integrase inhibitor-based ART 20 weeks before delivery was 0·36 (0·14-0·94) compared with those initiating non-nucleoside reverse transcriptase inhibitor (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: Vertical transmission probability varies by maternal immunological 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 vertical transmission outcomes. FUNDING: National Institutes of Health, UNAIDS, and UK Research and Innovation.