Global and regional molecular epidemiology of HIV-1 during 1990–2024: systematic review, global survey, and analysis of prevalence

Background: The extensive genetic diversity of HIV presents major challenges to treatment and prevention. We aimed to estimate the global and regional distribution of HIV-1 subtypes and recombinants during 1990–2024. Methods: We conducted a systematic literature review by searching PubMed, Embase, Global Health, and CINAHL for country-specific HIV-1 subtyping data published between Jan 1, 2022, and Jan 22, 2025, and a global survey of the Global HIV Molecular Epidemiology Collaboration for unpublished data collected between 2016 and 2024. We included primary HIV-1 subtyping data with ≥20 samples and known country and years of sample collection during 1990–2024. We excluded publications and survey responses that had no or incomplete subtyping data, were restricted to specific HIV-1 variants, included superinfections, or used secondary data. These data were combined with HIV-1 subtyping data previously collected between 1990 and 2021. Data were aggregated by country for six time periods (1990–99, 2000–04, 2005–09, 2010–14, 2015–19, and 2020–24). Proportions of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) were calculated by country and period and were weighted using UNAIDS country estimates of numbers of people living with HIV to estimate regional and global HIV-1 variant proportions. The systematic review is registered with PROSPERO, CRD42017067164. Findings: HIV-1 subtyping data were available for 1 395 222 samples from 154 countries during 1990–2024. In 2020–24, subtype C accounted for 48·7% (95% CI 48·3–49·1) of global HIV-1 infections, followed by subtype A (11·5%; 10·9–12·1), subtype B (10·3%; 10·0–10·5) URFs (5·3%; 4·4–6·3), CRF02_AG (5·1%; 4·5–5·8), CRF01_AE (5·1%; 4·8–5·4), other CRFs (3·9%; 3·3–4·5), subtype G (3·1%; 2·1–4·1), subtype D (3·0%; 2·7–3·3), and CRF07_BC (2·1%; 2·0–2·1). Subtypes F, H, J, K, and L combined accounted for 1·1% of infections and unspecified recombinants for 0·9% (0·7–1·0). HIV-1 variants are differentially distributed across regions, with subtype C dominating in southern Africa; Ethiopia, Eritrea, and Djibouti; and south Asia; subtype A in east Africa and eastern Europe and central Asia; subtype B in North America, Latin America, and western and central Europe; CRF01_AE in southeast Asia; and CRF07_BC in east Asia. Central Africa exhibited the greatest HIV-1 diversity. Global HIV-1 variant distributions were broadly stable during 2000–24, but notable regional changes included increases of HIV-1 recombinants in western and central Europe and of CRF07_BC in east Asia. Interpretation: Global and regional HIV-1 genetic diversity is complex and evolving, affecting the efficacy of diagnostic and viral load assays, emergence of drug resistance, and vaccine development. Continued surveillance of spatiotemporal trends in HIV-1 genetic diversity is essential. Funding: Nuffield Department of Population Health, University of Oxford, UK.