Transmission Dynamics of HIV-1 CRF01_AE in Indonesia

Résumé fourni par la source

Conference poster #47 presented at the 31st International Dynamics & Evolution of Human Viruses Conference (formerly International Workshop on HIV Dynamics & Evolution), Squamish, British Columbia, Canada, 19–22 June 2024. Background. Indonesia has the largest HIV burden in Southeast Asia outside the highest-prevalence countries; CRF01_AE accounts for the majority of circulating HIV-1 strains. The genetic relationships andtransmission patterns within and between Indonesian regions and key populations remain incompletely characterised because <0.5% of total diagnosed cases have publicly deposited sequences. Methods. Selected participants enrolled in the INA-PROACTIVE observational longitudinal cohort (NCT03663920; INA-RESPOND; 4,329 outpatients enrolled across 19 Indonesian hospitals, January 2018 – June 2020). Inclusion: 72 individuals with virologic failure on first-line antiretroviral therapy and 27 newly diagnosed individuals. Near full-length genomic Sanger sequencing of the HIV-1 pol region (protease 1–99, reverse transcriptase 1–560, integrase 1–288) was performed on plasma-derived virus. Subtype assignment used REGA HIV-1 Subtyping Tool v3.0 with recombination junctions confirmed by jpHMM. Time-scaled phylogenetic reconstruction was performed in BEAST2 using a selected genomic region (HXB2 2253–3295, 1,043 bp) with 77 Indonesian CRF01_AE sequences and 278 curated regional reference sequences (LANL HIV Database). Drug-resistance-associated mutations were inferred from the Stanford HIV Drug Resistance Database. Findings. (1) Multiple CRF01_AE introductions to Indonesia occurred in the 1980s, but most current sequences (49/77) descended from a single founder node dated to the late 1980s; a small number sharerecent common ancestors with sequences from regional countries. (2) Two transmission clusters were identified in Sumatra (Batam–Medan and Banda Aceh–Medan). (3) HIV from vertical-transmission cases shared recent common ancestors with sequences from heterosexual and men-who-have-sex-with-men (MSM) transmissionroutes across distant geographic locations, consistent with bridging across key populations and regions. (4) Resistance mutations in virologic failures: M184V/I 84.5%, K219Q/E and D67N 20.7%, K65R 19%, Y181C/I 41.4%, K103N 27.6%, G190A/S 29.3%. Paediatric participants showed substantially higher proportions of thymidine-analogue mutations (TAMs; 38.5%) than adults (2.2%), consistent with prolonged AZT exposure under paediatric national ART guidelines. Conclusion. Most circulating Indonesian CRF01_AE descend from a single late-1980s founder and are transmitted across heterogeneous risk groups and geographic regions, including vertical transmissionand recent infections. Drug-resistance patterns reflect the agents prescribed in first-line therapy and the paediatric treatment-history archetype. Public-health intervention should target the general population and emphasise antiretroviral adherence support. Funded in whole or in part by Ministry of Health, Republic of Indonesia; and Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract HHSN261201500003I (IDIQ) and Task Order HHSN26100060.

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