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

Background: Eliminating HIV vertical transmission (VT) and is a global priority. Estimates of paediatric HIV infections are commonly derived through mathematical models relying on rates of VT stratified by maternal immunological and treatment status from literature, namely the UNAIDS-supported Spectrum AIDS Impact Module (Spectrum-AIM) to assess progress towards eliminating VT. Default VT probabilities were last updated in 2018, since then there have been substantial changes to service delivery and ART regimens.

Methods: We aimed to (1) update the systematic review of VT probabilities by maternal status compatible with Spectrum-AIM, (2) conduct a meta-regression to systematically pool studies to estimate VT probabilities with statistical uncertainty, and (3) assess determinants of VT, including maternal viral load. We searched PubMed, Embase, Global Health Database, WHO Global Index Medicus, CINAHL Complete, and Cochrane CENTRAL for peer-reviewed articles in English from all geographic regions with data on VT from randomized controlled trials, cohort studies, or observational studies. We excluded sources that did not stratify VT by maternal treatment or immunological status. We fit four meta-regression models to produce VT probability estimates compatible with stratifications used in Spectrum-AIM and assessed how updated VT probabilities estimated new paediatric infections compared to default parameters in Spectrum-AIM. We conducted subgroup analyses to assess how study inclusion affected model estimates. Finally, we fit a meta-regression model to assess ART class and initiation timing on viral load suppression at delivery.

Findings: The updated systematic review identified 24 new studies published between January 2018 and February 2024. Combined with previous review data, 110 studies were included in the meta-regression analysis. Estimates were broadly consistent with previous reviews. For women not receiving PMTCT, the odds of perinatal transmission decreased by 0.20 (0.16-0.25) for each 100 mm ³ increase in median CD4 of the study population. Among women on ART during pregnancy, each additional week on ART before delivery reduced the odds of VT by 5.6% (4.3%-6.8%). ART regimen class affected VT probability; the odds ratio of perinatal VT among WLHIV who initiated an INSTI-based regimen versus a NNRTI-based regimen 20 weeks before delivery was 0.355 (0.140-0.898). However, this effect was confounded by study region. Viral load suppression at delivery was significantly lower among women who started ART late during pregnancy (p=0.02), but did not significantly differ by ART class (p>0.05).

Interpretation: Vertical transmission rates vary substantially according to maternal immunological stage, prophylactic regimen, and timing of treatment initiation. Time of initiation on ART before delivery was strongly associated with viral load suppression at delivery. Our estimates and their uncertainty can be used in Spectrum-AIM to produce estimates of paediatric incidence to inform funding and monitor progress towards eliminating VT.

Funding: National Institutes of Health, UNAIDS, and the Medical Research Council.