{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:56:26Z","timestamp":1790016986277,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"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>Highly active antiretroviral (ARV) therapy has been used for many years, but the use in low- and middle-income countries of antiretroviral drugs with low genetic barrier to resistance, combined with limited availability of viral load testing, has led to higher rates of acquired drug resistance, sustaining the rate of transmitted drug resistance. Here, we describe the evolution of ARV drugs with the ongoing development of injectable long-acting forms and the requirements regarding all new ARV drugs (i.e., no transmitted drug resistance, no cross-resistance and high genetic barrier to resistance). Then, we report the evolution of both transmitted and acquired resistance regarding new ARV drugs. The WHO has set very ambitious but motivating goals for HIV testing, treatment and viral suppression, aiming to achieve rates of 95% for all three by 2025. Reaching these goals requires a wide implementation and use of close virological monitoring in LMICs.<\/jats:p>","DOI":"10.3390\/v15020540","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T03:37:24Z","timestamp":1676432244000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Future of Antiretroviral Drugs and Evolution of HIV-1 Drug Resistance"],"prefix":"10.3390","volume":"15","author":[{"given":"Charlotte","family":"Charpentier","sequence":"first","affiliation":[{"name":"Service de Virologie, Universit\u00e9 Paris Cit\u00e9, INSERM, IAME, UMR 1137, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9017-4941","authenticated-orcid":false,"given":"Quentin","family":"Le Hingrat","sequence":"additional","affiliation":[{"name":"Service de Virologie, Universit\u00e9 Paris Cit\u00e9, INSERM, IAME, UMR 1137, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine Marie","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Service de Virologie, Universit\u00e9 Paris Cit\u00e9, INSERM, IAME, UMR 1137, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Damond","sequence":"additional","affiliation":[{"name":"Service de Virologie, Universit\u00e9 Paris Cit\u00e9, INSERM, IAME, UMR 1137, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Descamps","sequence":"additional","affiliation":[{"name":"Service de Virologie, Universit\u00e9 Paris Cit\u00e9, INSERM, IAME, UMR 1137, AP-HP, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","unstructured":"VanderVeen, L., Margot, N., Naik, V., Dvory-Sobol, H., Rhee, M., and Callebaut, C. (August, January 29). Resistance analysis of long-acting lenacapavir in treatment-na\u00efve people with HIV at 54 weeks. Proceedings of the AIDS 2022 Conference, Montreal, QC, Canada."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/infdis\/jiac364","article-title":"Resistance analyses in highly treatment-experienced people with Human Immunodeficiency Virus (HIV) treated with the novel capsid HIV inhibitor Lenacapavir","volume":"226","author":"Margot","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e668","DOI":"10.1016\/S2352-3018(21)00184-3","article-title":"Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: Week 124 results of the open-label phase 3 FLAIR study","volume":"8","author":"Orkin","year":"2021","journal-title":"Lancet HIV"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e679","DOI":"10.1016\/S2352-3018(21)00185-5","article-title":"Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: A randomised, multicentre, open-label, phase 3b, non-inferiority study","volume":"8","author":"Jaeger","year":"2021","journal-title":"Lancet HIV"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/AAC.04201-14","article-title":"In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways","volume":"59","author":"Feng","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/cid\/ciaa822","article-title":"Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate (TDF) versus Efavirenz\/Emtricitabine\/TDF in treatment-naive adults with Human Immunodeficiency Virus Type 1 infection: Week 96 results of the randomized, double-blind, Phase 3 DRIVE-AHEAD non inferiority trial","volume":"73","author":"Orkin","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/S2352-3018(19)30336-4","article-title":"Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial","volume":"7","author":"Molina","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/S0140-6736(12)61038-1","article-title":"Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: A global collaborative study and meta-regression analysis","volume":"380","author":"Gupta","year":"2012","journal-title":"Lancet"},{"key":"ref_9","first-page":"ciac972","article-title":"Transmitted drug resistance to integrase based first-line HIV antiretroviral regimens in the Mediterranean Europe","volume":"26","author":"Fuentes","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","unstructured":"TenoRes Study Group (2016). Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: A multicentre retrospective cohort study. Lancet Infect. Dis., 16, 565\u2013575."},{"key":"ref_11","unstructured":"Semengue, E.N.J., Santoro, M.M., Ndze, V.N., Dambaya, B., Takou, D., Teto, G., Nka, A.D., Fabeni, L., Wiyeh, A., and Ceccherini-Silberstein, F. (2022, January 8\u201310). HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis. Proceedings of the European Meeting on HIV & Hepatitis, Paris, France."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"ofac148","DOI":"10.1093\/ofid\/ofac148","article-title":"Dolutegravir resistance in Malawi\u2019s national HIV treatment program","volume":"9","author":"Chipungu","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e0164521","DOI":"10.1128\/AAC.01645-21","article-title":"Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study","volume":"66","author":"Vavro","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/jac\/dkx042","article-title":"Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies\/mL: A 2014 French nationwide study","volume":"72","author":"Assoumou","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0175121","DOI":"10.1128\/aac.01751-21","article-title":"Week 96 genotypic and phenotypic results of the fostemsavir Phase 3 BRIGHTE study in heavily treatment-experienced adults living with multidrug-resistant HIV-1","volume":"66","author":"Gartland","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1128\/JVI.02237-10","article-title":"Loss of asparagine-linked glycosylation sites in variable region 5 of human immunodeficiency virus type 1 envelope is associated with resistance to CD4 antibody ibalizumab","volume":"85","author":"Toma","year":"2011","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1016\/j.biocel.2008.04.007","article-title":"2\u2032-deoxy-4\u2032-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants","volume":"40","author":"Kawamoto","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0013322","DOI":"10.1128\/aac.00133-22","article-title":"Islatravir has a high barrier to resistance and exhibits a differentiated resistance profile from approved nucleoside reverse transcriptase inhibitors (NRTIs)","volume":"66","author":"Diamond","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/jac\/dky464","article-title":"Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients","volume":"74","author":"Santoro","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/jac\/dkaa401","article-title":"In vitro cross-resistance to doravirine in a panel of HIV-1 clones harbouring multiple NNRTI resistance mutations","volume":"76","author":"Saladini","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1093\/jac\/dkaa060","article-title":"Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients","volume":"75","author":"Marcelin","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/jac\/dkab503","article-title":"Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study","volume":"77","author":"Margot","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e02057-20","DOI":"10.1128\/AAC.02057-20","article-title":"Absence of Lenacapavir (GS-6207) phenotypic resistance in HIV gag cleavage site mutants and in isolates with resistance to existing drug classes","volume":"65","author":"Margot","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12977-018-0420-7","article-title":"Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants","volume":"15","author":"Smith","year":"2018","journal-title":"Retrovirology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:36:04Z","timestamp":1760121364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/2\/540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["v15020540"],"URL":"https:\/\/doi.org\/10.3390\/v15020540","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}