{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:04:01Z","timestamp":1788433441057,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014118","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["NIH R01 AI124718"],"award-info":[{"award-number":["NIH R01 AI124718"]}]},{"name":"NIH","award":["AI138801 and AI060354"],"award-info":[{"award-number":["AI138801 and AI060354"]}]},{"name":"NIH","award":["NIH P30AI050409"],"award-info":[{"award-number":["NIH P30AI050409"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>HIV-1 drug resistance remains a major challenge to treatment and control efforts, particularly in sub-Saharan Africa (sSA). However, standard resistance genotyping does not adequately capture linked drug resistance mutations within the viral quasispecies that may influence virologic failure (VF). We used a next-generation sequencing primer ID (NGS-Primer ID) assay to characterize linked HIV-1 drug resistance mutations in plasma from participants in the Resistance Testing to Improve Management of Virologic Failure (REVAMP) study who had detectable viremia on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) and were maintained on NNRTI-based regimens. For each participant, we calculated a weighted genotypic susceptibility score (wGSS) based on the GSS of each reported pattern and its sequence-supported frequency within the sample. Plasma specimens from 108 participants were sequenced. Sanger sequencing showed a median GSS of 1.0 (IQR, 1.0-2.0), whereas NGS-Primer ID identified a median of 10 distinct resistance patterns per participant (IQR, 5\u201317), with 67% (IQR, 8\u201392) of reported DRM-pattern frequency within participants corresponding to linked dual-class mutations. A broad spectrum of drug-susceptible and resistant- DRM patterns were observed, with the median difference between the highest and lowest pattern-specific GSS being 2.0 (2.0-2.75). Within each participant, a median of 10% of reported patterns showed less resistance, while 19% showed more resistance compared to that predicted by Sanger sequencing. Individuals with persistent VF had significantly lower wGSS at study entry than those who later achieved virologic re-suppression (median, 1.3 vs 2.1; p\u2009&lt;\u20090.001). NGS-Primer ID revealed substantial intra-host diversity in linked HIV-1 drug resistance patterns that was not captured by conventional Sanger sequencing. Incorporating linked resistance patterns into susceptibility assessment may improve prediction of subsequent virologic failure.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014118","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:42:07Z","timestamp":1778607727000},"page":"e1014118","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extensive diversity and impact of drug-resistant HIV-1 variants in individuals with prior virologic failure"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-1010","authenticated-orcid":true,"given":"Melendhran","family":"Pillay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish 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