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APOBEC-signature mutations reflect G\u2192A 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We retrospectively analysed plasma HIV-1 NGS-sequences from antiretroviral-naive individuals in 2022\u20132023. 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n APOBEC-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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/infdis\/jiag277","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T11:22:30Z","timestamp":1780312950000},"page":"e477-e485","source":"Crossref","is-referenced-by-count":0,"title":["HIV-1 APOBEC-context Mutations Detected by Next-Generation Sequencing in Plasma: Implications for Drug Resistance Interpretation"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2685-3036","authenticated-orcid":false,"given":"Marta","family":"Illescas-L\u00f3pez","sequence":"first","affiliation":[{"name":"Hospital Universitario de San Cecilio de Granada, Instituto de Investigaci\u00f3n Ibs.Granada, Ciber de Enfermedades Infecciosas Ciberinfec , Madrid 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