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This case\u2010control study compared virologic nonresponder children (two viral loads [VLs]\u2009\u2265\u2009200 copies\/mL within 2 years of ART) and responder children (two VLs\u2009&lt;\u2009200 copies\/mL after six months of ART) infected with HIV\u20101 initiated on nonnucleoside reverse\u2010transcriptase inhibitor (NNRTI)\u2010based ART. The partial reverse\u2010transcriptase gene of HIV\u20101 in cell\u2010associated DNA was genotyped using next\u2010generation sequencing (NGS; Illumina; threshold 0.5%; at baseline and month six of ART) and in cell\u2010free RNA (concurrently and at virological failure; VL\u2009&gt;\u20091000 copies\/mL at \u2265\u200912 months of ART) using the Sanger method. Among 30 nonresponders and 37 responders, baseline differences were insignificant while adherence, VL, and drug resistance mutations (DRMs) observed at month six differed significantly (\n<jats:italic>P<\/jats:italic>\u2009\u2265\u20090.05). At month six, NGS estimated a higher number of DRMs compared with Sanger (50% vs 33%; \n<jats:italic>P<\/jats:italic>\u2009=\u20090.001). Among the nonresponders carrying a resistant virus (86.6%) at virological failure, 26% harbored clinically relevant low\u2010frequency DRMs in the cell\u2010associated DNA at month six (0.5%\u201020%; K103N, G190A, Y181C, and M184I). Plasma VL of &gt;\u20093 log\n<jats:sub>10<\/jats:sub>copies\/mL (AOR, 30.4; 95% CI, 3.3\u2010281; \n<jats:italic>P<\/jats:italic>\u2009=\u20090.003) and treatment\u2010relevant DRMs detected in the cell\u2010associated DNA at month six (AOR, 24.2; 95% CI, 2.6\u2010221; \n<jats:italic>P<\/jats:italic>\u2009=\u20090.005) were independently associated with increased risk for early virological failure. Our findings suggest that treatment\u2010relevant DRMs acquired in cell\u2010associated DNA during the first six months of ART can predict virological failure in children initiated on NNRTI\u2010based ART.<\/jats:p>","DOI":"10.1002\/jmv.25413","type":"journal-article","created":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T01:09:27Z","timestamp":1548810567000},"page":"1036-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Viral evolution in the cell\u2010associated HIV\u20101 DNA during early ART can lead to drug resistance and virological failure in children"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-1367","authenticated-orcid":false,"given":"Bindu Parachalil","family":"Gopalan","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, St. John\u2019s Research Institute St. John\u2019s National Academy of Health Sciences  Bangalore 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