{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:06:30Z","timestamp":1768539990811,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA &lt;50 copies\/mL (median 202 days, range 21\u2013636). The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time\/day (ranges 1\u20132). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection.<\/jats:p>","DOI":"10.3390\/v15071444","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing Antiretroviral Therapy in Heavily ART-Experienced Patients with Multi-Class Resistant HIV-1 Using Proviral DNA Genotypic Resistance Testing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-8778","authenticated-orcid":false,"given":"Dominic","family":"Rauschning","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Department Ib of Internal Medicine, Bundeswehrzentralkrankenhaus Koblenz, R\u00fcbenacher Stra\u00dfe 170, 56072 Koblenz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira","family":"Ehren","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Heger","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Cologne, Faculty of Medicine and University Hospital Cologne, F\u00fcrst-P\u00fcckler-Stra\u00dfe 56, 50935 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-3026","authenticated-orcid":false,"given":"Elena","family":"Knops","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Cologne, Faculty of Medicine and University Hospital Cologne, F\u00fcrst-P\u00fcckler-Stra\u00dfe 56, 50935 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"F\u00e4tkenheuer","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany"},{"name":"Partner Site Bonn-Cologne, German Center for Infection Research (DZIF), 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults with and without HIV Infection, 2000\u20132016","volume":"3","author":"Marcus","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S871","DOI":"10.1093\/ofid\/ofz360.2188","article-title":"2510 Systematic Literature Review of Multiclass Resistance in Heavily Treatment Experienced Persons with, H.I.V","volume":"6","author":"Mauskopf","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"846943","DOI":"10.3389\/fmicb.2022.846943","article-title":"Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters","volume":"13","author":"Miranda","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.2147\/PPA.S142643","article-title":"Patient preferences for antiretroviral therapy: Effectiveness, quality of life, access and novel delivery methods","volume":"11","author":"Eaton","year":"2017","journal-title":"Patient Prefer. Adherence"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s40264-018-0698-3","article-title":"Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa","volume":"41","author":"Onoya","year":"2018","journal-title":"Drug. Saf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/jac\/dkm499","article-title":"Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): A balancing act","volume":"61","author":"Burgoyne","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","unstructured":"(2022, February 25). What\u2019s New in the Guidelines?|NIH [Internet], Available online: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-arv\/whats-new-guidelines."},{"key":"ref_8","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":"Sierra","year":"2015","journal-title":"Intervirology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12977-018-0444-z","article-title":"Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control","volume":"15","author":"Caetano","year":"2018","journal-title":"Retrovirology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"Chun","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jcv.2004.11.006","article-title":"Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART","volume":"33","author":"Chew","year":"2005","journal-title":"J. Clin. Virol. Off. Publ. Pan. Am. Soc. Clin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.ebiom.2019.02.016","article-title":"Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection","volume":"41","author":"Lenfant","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1093\/infdis\/jit311","article-title":"Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size","volume":"208","author":"Jain","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaaw5589","DOI":"10.1126\/scitranslmed.aaw5589","article-title":"The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation","volume":"11","author":"Abrahams","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brooks, K., Jones, B.R., Dilernia, D.A., Wilkins, D.J., Claiborne, D.T., McInally, S., Gilmour, J., Kilembe, W., Joy, J.B., and Allen, S.A. (2020). HIV-1 variants are archived throughout infection and persist in the reservoir. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008378"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1128\/JVI.01985-12","article-title":"An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral treatment suggests proliferation of HIV-infected cells","volume":"87","author":"Wagner","year":"2013","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ofz533","DOI":"10.1093\/ofid\/ofz533","article-title":"Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment","volume":"7","author":"Ellis","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1089\/apc.2019.0198","article-title":"Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients","volume":"34","author":"Meybeck","year":"2020","journal-title":"AIDS Patient Care STDs"},{"key":"ref_19","unstructured":"(2023, May 30). Update of Recommendations on First- and Second-Line Antiretroviral Regimens, Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/325892\/WHO-CDS-HIV-19.15-eng.pdf."},{"key":"ref_20","unstructured":"Marlowe, N., Dileanis, J., and Elbeik, T. (2023, June 13). Evaluation of Applied Biosystems ViroSeqTM HIV-1 Genotyping System Version 2 for the Detection of Drug Resistance Mutations in Research Clinical Plasma Samples. In Durban, South Africa. Available online: https:\/\/tools.thermofisher.com\/content\/sfs\/brochures\/cms_039715.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6824","DOI":"10.1128\/AAC.01490-15","article-title":"HIV Drug Resistance Testing by High-Multiplex \u201cWide\u201d Sequencing on the MiSeq Instrument","volume":"59","author":"Lapointe","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","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":"ref_23","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1177\/0956462418778705","article-title":"Long-term HIV\/AIDS survivors: Patients living with HIV infection retained in care for over 20 years. What have we learned?","volume":"29","author":"Krentz","year":"2018","journal-title":"Int. J. STD AIDS"},{"key":"ref_24","first-page":"292","article-title":"HIV-1 drug resistance and resistance testing","volume":"46","author":"Clutter","year":"2016","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_25","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":"ref_26","doi-asserted-by":"crossref","unstructured":"Derache, A., Shin, H.S., Balamane, M., White, E., Israelski, D., Klausner, J.D., Freeman, A.H., and Katzenstein, D. (2015). HIV drug resistance mutations in proviral DNA from a community treatment program. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117430"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1093\/jac\/dkt474","article-title":"Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz","volume":"69","author":"Geretti","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","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":"ref_29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00126334-200404150-00005","article-title":"Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy","volume":"35","author":"Verhofstede","year":"2004","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_30","first-page":"E318","article-title":"Analysis of intracellular human immunodeficiency virus (HIV)-1 drug resistance mutations in multi-failed HIV-1-infected patients treated with a salvage regimen: 72-week follow-up","volume":"19","author":"Falasca","year":"2013","journal-title":"Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/jac\/dkv395","article-title":"Drug resistance and tropism as markers of the dynamics of HIV-1 DNA quasispecies in blood cells of heavily pretreated patients who achieved sustained virological suppression","volume":"71","author":"Gantner","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1093\/jac\/dky316","article-title":"Utility of HIV-1 DNA genotype in determining antiretroviral resistance in patients with low or undetectable HIV RNA viral loads","volume":"73","author":"Boukli","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jcv.2016.07.007","article-title":"Genotypic resistance test in proviral DNA can identify resistance mutations never detected in historical genotypic test in patients with low level or undetectable, HIV-RNA","volume":"82","author":"Zaccarelli","year":"2016","journal-title":"J. Clin. Virol. Off. Publ. Pan. Am. Soc. Clin. Virol."},{"key":"ref_34","first-page":"56","article-title":"Comparison of HIV-1 resistance profiles in plasma RNA versus PBMC DNA in heavily treated patients in Honduras, a resource-limited country","volume":"3","author":"Diallo","year":"2012","journal-title":"Int. J. Mol. Epidemiol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1007\/s40121-022-00676-y","article-title":"HIV DNA Sequencing to Detect Archived Antiretroviral Drug Resistance","volume":"11","author":"Geretti","year":"2022","journal-title":"Infect. Dis. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2325958219849101","DOI":"10.1177\/2325958219849101","article-title":"Analysis of the Impact of Antiretroviral Drug Changes on Survival of Patients with Advanced-Stage AIDS with Multidrug-Resistant HIV Infection","volume":"18","author":"Ma","year":"2019","journal-title":"J. Int. Assoc. Provid. AIDS Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"833","DOI":"10.3851\/IMP2076","article-title":"Pill burden in HIV infection: 20 years of experience","volume":"17","author":"Krentz","year":"2012","journal-title":"Antivir. Ther."},{"key":"ref_38","unstructured":"Doctor, J. (2022, May 29). Anticholinergic Medications Associated with Falls and Frailty in People Ageing with HIV [Internet]. Available online: https:\/\/www.croiconference.org\/abstract\/anticholinergic-medications-associated-with-falls-and-frailty-in-people-with-hiv\/."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1517\/17425255.2013.781153","article-title":"Clinical pharmacokinetics of antiretroviral drugs in older persons","volume":"9","author":"Schoen","year":"2013","journal-title":"Expert. Opin. Drug. Metab. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1093\/cid\/ciu046","article-title":"Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials","volume":"58","author":"Nachega","year":"2014","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1089\/aid.2008.0141","article-title":"Relationship between adherence level, type of the antiretroviral regimen, and plasma HIV type 1 RNA viral load: A prospective cohort study","volume":"24","author":"Martin","year":"2008","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_42","first-page":"115","article-title":"One-pill once-a-day HAART: A simplification strategy that improves adherence and quality of life of HIV-infected subjects","volume":"4","author":"Airoldi","year":"2010","journal-title":"Patient Prefer. Adherence"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1080\/09540120412331305098","article-title":"Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence","volume":"17","author":"Mannheimer","year":"2005","journal-title":"AIDS Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s40271-021-00524-0","article-title":"Patient-Reported Outcomes Through 1 Year of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine Administered Every 4 or 8 Weeks (ATLAS-2M)","volume":"14","author":"Chounta","year":"2021","journal-title":"Patient"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Varghese, V., Wang, E., Babrzadeh, F., Bachmann, M.H., Shahriar, R., Liu, T., Mappala, S.J.M., Gharizadeh, B., Fessel, W.J., and Katzenstein, D. (2010). Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010992"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/QAD.0b013e3283427dcb","article-title":"Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy","volume":"25","author":"Goodman","year":"2011","journal-title":"AIDS"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/jama.2022.22246","article-title":"Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society\u2013USA Panel","volume":"329","author":"Gandhi","year":"2023","journal-title":"JAMA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:01:38Z","timestamp":1760126498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,27]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["v15071444"],"URL":"https:\/\/doi.org\/10.3390\/v15071444","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,27]]}}}