{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:49:48Z","timestamp":1792500588935,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010682","name":"Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010682","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005235","name":"IAS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The improved efficacy and tolerability of newer antiretroviral drugs, as well as the introduction of long-acting regimens, have prompted more frequent therapy switches in individuals on suppressive antiretroviral therapy (ART). For these individuals, the assessment of HIV drug resistance using DNA from peripheral blood lymphocytes has become increasingly popular. However, compared with HIV RNA-based analyses, implementation of HIV DNA testing as an alternative approach in clinical care requires new documented quality-assessment procedures and clinical validation. Furthermore, the use of HIV DNA to assess drug resistance has some distinct technical and biologic challenges that are relevant to the clinical management of people with HIV. This Viewpoint article addresses the issues relevant to clinical virologists and treating physicians for the interpretation of drug-resistance testing or subtype assessment based on DNA analysis, when HIV RNA genotypic assessment is not possible.<\/jats:p>","DOI":"10.1093\/cid\/ciaf161","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T10:05:24Z","timestamp":1743588324000},"page":"e132-e136","source":"Crossref","is-referenced-by-count":30,"title":["Utilizing HIV Proviral DNA to Assess for the Presence of HIV Drug Resistance"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-8891","authenticated-orcid":false,"given":"Annemarie M","family":"Wensing","sequence":"first","affiliation":[{"name":"Department of Global Health and Bio-Ethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]},{"name":"Ezintsha, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Charpentier","sequence":"additional","affiliation":[{"name":"Department of Virology, Paris Cit\u00e9 University and Bichat-Claude Bernard Hospital , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6855-3472","authenticated-orcid":false,"given":"Vincent","family":"Calvez","sequence":"additional","affiliation":[{"name":"Department of Virology, Sorbonne Universit\u00e9 School of Medicine, INSERM, Institut Pierre Louis d'Epid\u00e9miologie et de Sant\u00e9 Publique, AP-HP, H\u00f4pitaux Universitaires Piti\u00e9 Salp\u00eatri\u00e8re\u2014Charles Foix, Laboratoire de Virologie , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ceccherini-Silberstein","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-6723","authenticated-orcid":false,"given":"Huldrych F","family":"G\u00fcnthard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and Institute of Medical Virology, University of Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"International Antiviral Society\u2013USA , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-691X","authenticated-orcid":false,"given":"Roger","family":"Paredes","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and irsiCaixa, Hospital Universitari Germans Trias i Pujol , Badalona ,","place":["Spain"]},{"name":"Universitat Polit\u00e8cnica de Catalunya - BarcelonaTech , Terrassa ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0962-9254","authenticated-orcid":false,"given":"Douglas D","family":"Richman","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine, University of California San Diego , San Diego, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"2025110901583720700_ciaf161-B1","article-title":"2025 Update of the drug resistance mutations in HIV-1","author":"Wensing","journal-title":"Top Antivir Med"},{"key":"2025110901583720700_ciaf161-B2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/cid\/ciy463","article-title":"Human immunodeficiency virus drug resistance: 2018 recommendations of the International Antiviral Society-USA panel","volume":"68","author":"G\u00fcnthard","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2025110901583720700_ciaf161-B3","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1473-3099(24)00289-5","article-title":"Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial","volume":"24","author":"Kityo","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"2025110901583720700_ciaf161-B4","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.3390\/v15091811","article-title":"Sensitive HIV-1 DNA pol next-generation sequencing for the characterisation of archived antiretroviral drug resistance","volume":"15","author":"Botha","year":"2023","journal-title":"Viruses"},{"key":"2025110901583720700_ciaf161-B5","doi-asserted-by":"crossref","first-page":"e0005222","DOI":"10.1128\/cmr.00052-22","article-title":"Genotypic resistance testing of HIV-1 DNA in peripheral blood mononuclear cells","volume":"35","author":"Chu","year":"2022","journal-title":"Clin Microbiol Rev"},{"key":"2025110901583720700_ciaf161-B6","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1093\/jac\/dkad240","article-title":"Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV cohort study, a retrospective study from 1995 to 2018","volume":"78","author":"Jaha","year":"2023","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B7","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1093\/jac\/dkab149","article-title":"Assessment of intra-sample variability in HIV-1 DNA drug resistance genotyping","volume":"76","author":"Milliere","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B8","first-page":"158","article-title":"HIV-1 DNA genotyping is often variable in repeat testing from single blood draws [CROI abstract 438]. Special issue: abstracts from the CROI 2024 Conference on Retroviruses and Opportunistic Infections","volume":"29","author":"Antoni","year":"2021","journal-title":"Top Antivir Med"},{"issue":"Suppl 1","key":"2025110901583720700_ciaf161-B9","doi-asserted-by":"crossref","first-page":"S398","DOI":"10.1093\/ofid\/ofaa439.883","article-title":"Results of repeat HIV-1 DNA resistance tests are highly concordant","volume":"7","author":"Curanovic","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2025110901583720700_ciaf161-B10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000431093","article-title":"Proviral DNA as a target for HIV-1 resistance analysis","volume":"58","author":"Lubke","year":"2015","journal-title":"Intervirology"},{"key":"2025110901583720700_ciaf161-B11","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1128\/JCM.06689-11","article-title":"Automating HIV drug resistance genotyping with RECall, a freely accessible sequence analysis tool","volume":"50","author":"Woods","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2025110901583720700_ciaf161-B12","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1128\/JCM.37.7.2291-2296.1999","article-title":"Worldwide evaluation of DNA sequencing approaches for identification of drug resistance mutations in the human immunodeficiency virus type 1 reverse transcriptase","volume":"37","author":"Schuurman","year":"1999","journal-title":"J Clin Microbiol"},{"key":"2025110901583720700_ciaf161-B13","doi-asserted-by":"crossref","first-page":"ofad146","DOI":"10.1093\/ofid\/ofad146","article-title":"HIV-1 DNA testing in viremic patients identifies more drug resistance than HIV-1 RNA testing","volume":"10","author":"Curanovic","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2025110901583720700_ciaf161-B14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","volume":"22","author":"Bruner","year":"2016","journal-title":"Nat Med"},{"key":"2025110901583720700_ciaf161-B15","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1097\/QAD.0000000000002850","article-title":"Drug resistance mutations in HIV provirus are associated with defective proviral genomes with hypermutation","volume":"35","author":"Li","year":"2021","journal-title":"AIDS"},{"key":"2025110901583720700_ciaf161-B16","doi-asserted-by":"crossref","first-page":"e0225352","DOI":"10.1371\/journal.pone.0225352","article-title":"Analysis of unusual and signature APOBEC-mutations in HIV-1 pol next-generation sequences","volume":"15","author":"Tzou","year":"2020","journal-title":"PLoS One"},{"key":"2025110901583720700_ciaf161-B17","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/infdis\/jiad292","article-title":"Absence of proviral human immunodeficiency virus (HIV) type 1 evolution in early-treated individuals with HIV switching to dolutegravir monotherapy during 48 weeks","volume":"228","author":"Jorimann","year":"2023","journal-title":"J Infect Dis"},{"key":"2025110901583720700_ciaf161-B18","doi-asserted-by":"crossref","first-page":"105551","DOI":"10.1016\/j.jcv.2023.105551","article-title":"Temporal trend of drug-resistance and APOBEC editing in PBMC genotypic resistance tests from HIV-1 infected virologically suppressed individuals","volume":"168","author":"Armenia","year":"2023","journal-title":"J Clin Virol"},{"key":"2025110901583720700_ciaf161-B19","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1056\/NEJMoa041305","article-title":"Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy","volume":"351","author":"Jourdain","year":"2004","journal-title":"N Engl J Med"},{"key":"2025110901583720700_ciaf161-B20","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1086\/587657","article-title":"Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children","volume":"46","author":"Cressey","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2025110901583720700_ciaf161-B21","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1097\/QAD.0000000000002883","article-title":"Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis","volume":"35","author":"Cutrell","year":"2021","journal-title":"AIDS"},{"key":"2025110901583720700_ciaf161-B22","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/jac\/dkx511","article-title":"Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen","volume":"73","author":"Charpentier","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B23","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/jac\/dkt003","article-title":"Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses","volume":"68","author":"Lambert-Niclot","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B24","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/nar\/gkg100","article-title":"Human immunodeficiency virus reverse transcriptase and protease sequence database","volume":"31","author":"Rhee","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2025110901583720700_ciaf161-B25","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1128\/JCM.00893-15","article-title":"Genotypic tropism testing in HIV-1 proviral DNA can provide useful information at low-level viremia","volume":"53","author":"Fabeni","year":"2015","journal-title":"J Clin Microbiol"},{"key":"2025110901583720700_ciaf161-B26","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/jac\/dkt426","article-title":"Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy","volume":"69","author":"Meini","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B27","doi-asserted-by":"crossref","first-page":"e14638","DOI":"10.1371\/journal.pone.0014638","article-title":"Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity","volume":"6","author":"Paquet","year":"2011","journal-title":"PLoS One"},{"key":"2025110901583720700_ciaf161-B28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/aid.2008.0159","article-title":"Dynamics of NRTI resistance mutations during therapy interruption","volume":"25","author":"Trignetti","year":"2009","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2025110901583720700_ciaf161-B29","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/jac\/dkr157","article-title":"Evolutionary pathways of transmitted drug-resistant HIV-1","volume":"66","author":"Pingen","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B30","doi-asserted-by":"crossref","first-page":"e1004722","DOI":"10.1371\/journal.ppat.1004722","article-title":"Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds","volume":"11","author":"Yang","year":"2015","journal-title":"PLoS Pathog"},{"key":"2025110901583720700_ciaf161-B31","doi-asserted-by":"crossref","first-page":"e1006895","DOI":"10.1371\/journal.ppat.1006895","article-title":"Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics","volume":"14","author":"Kuhnert","year":"2018","journal-title":"PLoS Pathog"},{"key":"2025110901583720700_ciaf161-B32","doi-asserted-by":"crossref","first-page":"F83","DOI":"10.1097\/00002030-200006160-00001","article-title":"A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 study team for the Terry Beirn community programs for clinical research on AIDS","volume":"14","author":"Baxter","year":"2000","journal-title":"AIDS"},{"key":"2025110901583720700_ciaf161-B33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/00002030-200201250-00010","article-title":"Clinical utility of HIV-1 genotyping and expert advice: the Havana trial","volume":"16","author":"Tural","year":"2002","journal-title":"AIDS"},{"key":"2025110901583720700_ciaf161-B34","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(98)12291-2","article-title":"Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial [published correction appears in Lancet 1999;354(9184):1128]","volume":"353","author":"Durant","year":"1999","journal-title":"Lancet"},{"key":"2025110901583720700_ciaf161-B35","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/infdis\/170.5.1292","article-title":"Detection of drug resistance mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene: differences in semen and blood HIV-1 RNA and proviral DNA","volume":"170","author":"Kroodsma","year":"1994","journal-title":"J Infect Dis"},{"key":"2025110901583720700_ciaf161-B36","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1128\/jvi.70.11.7894-7899.1996","article-title":"Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients","volume":"70","author":"Havlir","year":"1996","journal-title":"J Virol"},{"key":"2025110901583720700_ciaf161-B37","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/jac\/dkq544","article-title":"Historical HIV-RNA resistance test results are more informative than proviral DNA genotyping in cases of suppressed or residual viraemia","volume":"66","author":"Wirden","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B38","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1468-1293.2012.01002.x","article-title":"Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed replication","volume":"13","author":"Delaugerre","year":"2012","journal-title":"HIV Med"},{"key":"2025110901583720700_ciaf161-B39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jgar.2022.07.022","article-title":"Virological efficacy of switch to DTG plus 3TC in a retrospective observational cohort of suppressed HIV-1 patients with or without past M184V: the LAMRES study","volume":"31","author":"Santoro","year":"2022","journal-title":"J Glob Antimicrob Resist"},{"key":"2025110901583720700_ciaf161-B40","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/jac\/dky130","article-title":"Dynamics of drug resistance-associated mutations in HIV-1 DNA reverse transcriptase sequence during effective ART","volume":"73","author":"Nouchi","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2025110901583720700_ciaf161-B41","doi-asserted-by":"crossref","first-page":"dlae194","DOI":"10.1093\/jacamr\/dlae194","article-title":"Clearance of archived integrase strand transfer inhibitors resistance mutations in people with virologically suppressed HIV infection","volume":"6","author":"Abdi","year":"2024","journal-title":"JAC Antimicrob Resist"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaf161\/62846615\/ciaf161.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/81\/4\/e132\/62846615\/ciaf161.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/81\/4\/e132\/62846615\/ciaf161.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T06:58:47Z","timestamp":1762671527000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/81\/4\/e132\/8104454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,3]]},"published-print":{"date-parts":[[2025,11,6]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaf161","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10,15]]},"published":{"date-parts":[[2025,4,3]]}}}