{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T06:38:17Z","timestamp":1780814297989,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chantal BIYA International Reference Centre for research on HIV\/AIDS prevention and management (CIRCB)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL\u2019s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI\/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V\/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges.<\/jats:p>","DOI":"10.3390\/v17010069","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-8661","authenticated-orcid":false,"given":"Alex Durand","family":"Nka","sequence":"first","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-683X","authenticated-orcid":false,"given":"Yagai","family":"Bouba","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"},{"name":"Faculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried Rooker","family":"Tsapi Lontsi","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"},{"name":"Department of Microbiology, Faculty of Science, University of Yaound\u00e9 1, Yaound\u00e9 P.O. Box 337, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7377-1652","authenticated-orcid":false,"given":"Davy-Hyacinte","family":"Gouissi Anguechia","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Teto","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-4299","authenticated-orcid":false,"given":"Aude christelle","family":"Ka\u2019e","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8768-2371","authenticated-orcid":false,"given":"Ezechiel Ngoufack Jagni","family":"Semengue","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-1436","authenticated-orcid":false,"given":"Collins","family":"Ambe Chenwi","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"},{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9","family":"Takou","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lum","family":"Forgwei","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Anim-Keng","family":"Tekoh","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie Minelle Kengni","family":"Ngueko","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette Bomgning","family":"Fokou","sequence":"additional","affiliation":[{"name":"Department of Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremiah","family":"Efakika Gabisa","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-8515","authenticated-orcid":false,"given":"Michel Carlos Tommo","family":"Tchouaket","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5194-6715","authenticated-orcid":false,"given":"Willy Leroi","family":"TognaPabo","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick Tambe","family":"Ayuk Ngwese","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky","family":"Njiki Bikoi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, University of Yaound\u00e9 1, Yaound\u00e9 P.O. Box 337, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Armenia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Colizzi","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-2631","authenticated-orcid":false,"given":"Marcel","family":"Yotebieng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicaise","family":"Ndembi","sequence":"additional","affiliation":[{"name":"Africa Centres for Disease Control and Prevention, Addis Ababa P.O. Box 3243, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-1114","authenticated-orcid":false,"given":"Maria-Mercedes","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ceccherini-Silberstein","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo-Federico","family":"Perno","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"},{"name":"Microbiology and Diagnostic Immunology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Ndjolo","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1501-2763","authenticated-orcid":false,"given":"Joseph","family":"Fokam","sequence":"additional","affiliation":[{"name":"Chantal BIYA International Reference Centre for Research on HIV\/AIDS Prevention and Management, Yaound\u00e9 P.O. Box 3077, Cameroon"},{"name":"Central Technical Group, National AIDS Control Committee, Yaound\u00e9 P.O. Box 1459, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","unstructured":"(2024, May 18). UNAIDS Global HIV & AIDS Statistics\u2014Fact Sheet. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12981-019-0252-0","article-title":"Viral suppression in adults, adolescents and children receiving antiretroviral therapy in Cameroon: Adolescents at high risk of virological failure in the era of \u201ctest and treat\u201d","volume":"16","author":"Fokam","year":"2019","journal-title":"AIDS Res. 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