ArticleInfection2026
Integrated analysis of HIV-1 drug resistance across reverse transcriptase, protease and integrase in india: gene-region-corrected prevalence and threshold-specific scoring from public sequence data.
Article in Infection, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeIndia carries the third-largest HIV-1 burden globally. The 2021 national transition to Tenofovir/Lamivudine/Dolutegravir (TLD) makes Integrase Strand Transfer Inhibitor resistance surveillance an urgent programmatic priority, yet no prior Indian study has simultaneously characterised all three pol gene regions using gene-region-corrected denominators or multi-threshold algorithmic scoring.
methodsWe retrieved 4,375 HIV-1 subtype C pol sequences from LANL and NCBI GenBank (November 2024). Gene-region-specific denominators were applied (RT, n = 2,879; Protease, n = 2,373; Integrase, n = 1,084). Mutations were classified per 2022 IAS-USA criteria; drug-level resistance was scored across four Stanford HIVdb v9.4 thresholds with Benjamini-Hochberg FDR correction. Mutation co-occurrence was assessed across 231 pairs simultaneously.
resultsNNRTI resistance was 36.7% (95% CI: 35.0-38.5%), NRTI resistance 25.4%, and dual-class resistance 23.0%; predominant mutations were M184V (19.2%), K103N (11.9%), and Y181C (8.7%). Composite HIVdb scoring detected TDF resistance in 12.1% (≥ Level 3) - four-fold higher than K65R-based counting alone (3.0%) - reflecting Thymidine Analogue Mutation cross-resistance. Nevirapine, Efavirenz, and Protease Inhibitor major resistance were 32.9%, 31.7%, and 4.0%, respectively. INSTI major resistance was 1.6% (95% CI: 0.9-2.4%); Q148H/K/R was entirely absent, and Dolutegravir/Bictegravir resistance was 0% at ≥Level 3. L74M prevalence was 11.3% (9.5-13.3%). Threshold sensitivity reached 9.4-fold for etravirine; co-occurrence analysis identified K65R+V106M enrichment (8.4-fold, FDR q < 0.001).
conclusionsAmong publicly available Indian sequences enriched for treatment-failure submissions, the complete absence of Q148-pathway mutations provides a bounded baseline among available pre-/early-TLD integrase sequences. The four-fold TDF resistance underestimation by conventional mutation counting and up to 9.4-fold threshold-dependent prevalence variation support composite algorithm-scored, threshold-specified reporting as a standard for database-level HIV drug resistance analyses.
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