ArticleThe Journal of infectious diseases2026
HIV-1 APOBEC-context Mutations Detected by Next-Generation Sequencing in Plasma: Implications for Drug Resistance Interpretation.
Article in The Journal of infectious diseases, 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
backgroundAPOBEC3-mediated cytidine deamination produces G→A substitutions in HIV genomes, described in proviral DNA but detectable in plasma HIV-1 RNA using NGS. APOBEC-signature mutations reflect G→A enrichment substitutions, whereas APOBEC-context mutations are substitutions at drug resistance-associated positions compatible with APOBEC editing. We evaluated theirprevalence and impact on resistance interpretation.
methodsWe retrospectively analysed plasma HIV-1 NGS-sequences from antiretroviral-naive individuals in 2022-2023. Sequencing was performed in participating laboratories, and FASTQ centrally reanalyzed using DeepChek. APOBEC-signature mutations, APOBEC-context drug resistance mutations (DRMs), and stop codons were assessed in protease, reverse transcriptase, and integrase at 1%, 3%, and 5% thesholds.
resultsAmong 290 individuals, 268 had complete NGS. At 1%, APOBEC-signature mutations were detected in 159 individuals and APOBEC-context DRMs in 64 (22%). Both patterns coexisted in 52 (18%), decreasing to 17 (6%) and 8 (3%) at 3% and 5% thresholds. Certain mutations, including M184I, G190E, G140S, and R263K, remained detectable at higher thresholds. R263K co-occurred with multiple APOBEC-signature mutations and stop codons indicating extensive APOBEC-mediated editing.
conclusionsAPOBEC-associated mutations are detectable in plasma HIV-1 RNA and may affect resistance interpretation. Conservative frequency thresholds (5%) APOBEC-signatures evaluation may reduce misclassification of APOBEC-induced variants as clinically relevant resistance.
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