{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:54:34Z","timestamp":1789764874487,"version":"4.0.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIRCB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Maintenance monotherapy with ritonavir-boosted darunavir has yielded variable outcomes and is not recommended. Trial samples offer valuable opportunities for detailed studies. We analysed samples from a 48 week trial in Cameroon to obtain a detailed characterization of drug resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Following failure of NNRTI-based therapy and virological suppression on PI-based therapy, participants were randomized to ritonavir-boosted darunavir (n = 81) or tenofovir disoproxil fumarate\/lamivudine +ritonavir-boosted lopinavir (n = 39). At study entry, PBMC-derived HIV-1 DNA underwent bulk Protease and Reverse Transcriptase (RT) sequencing. At virological rebound (confirmed or last available HIV-1 RNA \u2265 60 copies\/mL), plasma HIV-1 RNA underwent ultradeep Protease and RT sequencing and bulk Gag-Protease sequencing. The site-directed mutant T375A (p2\/p7) was characterized phenotypically using a single-cycle assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NRTI and NNRTI resistance-associated mutations (RAMs) were detected in 52\/90 (57.8%) and 53\/90 (58.9%) HIV-1 DNA samples, respectively. Prevalence in rebound HIV-1 RNA (ritonavir-boosted darunavir, n = 21; ritonavir-boosted lopinavir, n = 2) was 9\/23 (39.1%) and 10\/23 (43.5%), respectively, with most RAMs detected at frequencies \u226515%. The resistance patterns of paired HIV-1 DNA and RNA sequences were partially consistent. No darunavir RAMs were found. Among eight participants experiencing virological rebound on ritonavir-boosted darunavir (n = 12 samples), all had Gag mutations associated with PI exposure, including T375N, T375A (p2\/p7), K436R (p7\/p1) and substitutions in p17, p24, p2 and p6. T375A conferred 10-fold darunavir resistance and increased replication capacity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The study highlights the high resistance barrier of ritonavir-boosted darunavir while identifying alternative pathways of resistance through Gag substitutions. During virological suppression, resistance patterns in HIV-1 DNA reflect treatment history, but due to technical and biological considerations, cautious interpretation is warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad386","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T13:13:39Z","timestamp":1703769219000},"page":"339-348","source":"Crossref","is-referenced-by-count":7,"title":["A detailed characterization of drug resistance during darunavir\/ritonavir monotherapy highlights a high barrier to the emergence of resistance mutations in protease but identifies alternative pathways of resistance"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-8264","authenticated-orcid":false,"given":"Adam","family":"Abdullahi","sequence":"first","affiliation":[{"name":"arvard T.H. Chan School of Public Health Takemi Program in International Health, H , Boston, MA , USA"},{"name":"Cambridge Institute of Therapeutic Immunology & Infectious Disease , Cambridge , UK"},{"name":"Institute of Human Virology Nigeria , Abuja , Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Garcia","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Virology, Royal Free London NHS Foundation Trust , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Mafotsing","family":"Fopoussi","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Department, University of West Attica , Athens, Greece"},{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB) , Yaound\u00e9 , Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Beloukas","sequence":"additional","affiliation":[{"name":"Biomedical Sciences 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