{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:43:44Z","timestamp":1783665824602,"version":"3.55.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI120765"],"award-info":[{"award-number":["AI120765"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosglobalpublichealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Glob Public Health"],"abstract":"<jats:p>\n                    Compared to HIV-1, HIV-2 infection is characterized by lower viral loads and slower decline in CD4 cells, however the majority of people living with HIV-2 (PLWH2) progress to AIDS and will benefit from antiretroviral therapy. Mutations leading to protease inhibitor (PI) resistance in HIV-2 are poorly characterized, but have important implications for second-line therapy. We evaluated the phenotypic drug susceptibility impacts of HIV-2 protease changes which are identified in genotypic resistance tools. We generated a library of 54 full length HIV-2\n                    <jats:sub>ROD9<\/jats:sub>\n                    clones that included 21 individual protease mutations, alone or in various combinations. We generated eight additional clones containing combinations of changes observed in PI-treated PLWH2. We tested the clones in a single-cycle PI assay to determine darunavir (DRV) and lopinavir (LPV) EC\n                    <jats:sub>50<\/jats:sub>\n                    , and calculated fold change resistance relative to wild-type HIV-2\n                    <jats:sub>ROD9<\/jats:sub>\n                    . Four of the 21 amino acid changes tested alone conferred PI resistance: V47A and T56V conferred 4.1 and 2.9-fold resistance, respectively, to LPV, I50V conferred 4.6-fold resistance to DRV, and I54M conferred 5.5-fold resistance to DRV and 2.2-fold resistance to LPV. Other changes either lowered the EC\n                    <jats:sub>50<\/jats:sub>\n                    or caused no change. Some combinations including V47A, I50V, I54M, or T56V also conferred resistance, with EC\n                    <jats:sub>50<\/jats:sub>\n                    values 4.4 to 17-fold higher than wild-type. Six of eight PLWH2-derived strains were replication-competent: five exhibited resistance to LPV (&gt;8.8-fold resistance), and three exhibited resistance to DRV (&gt;4.7-fold). HIV-1 and HIV-2 are not equivalently susceptible to all antiretroviral agents and do not utilize identical pathways to resistance. We provide phenotypic evidence supporting the resistance role of changes in HIV-2 protease which do not have HIV-1 analogues, as well as evidence that analogues of \u201cmajor\u201d resistance changes in HIV-1 may have no resistance impacts in HIV-2, despite apparent treatment selection. These results should inform the HIV-2 genotypic resistance tools and help improve treatment for PLWH2.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgph.0005743","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:37:05Z","timestamp":1770230225000},"page":"e0005743","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotypic impacts of treatment-selected mutations in HIV-2 protease on darunavir and lopinavir susceptibility: Evaluating genotypic HIV-2 drug resistance tools"],"prefix":"10.1371","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6205-845X","authenticated-orcid":true,"given":"Dana N.","family":"Raugi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Nixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-6026","authenticated-orcid":true,"given":"Stephen E.","family":"Hawes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khardiata","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouhamadou Ba\u00efla","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadim","family":"Faye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binetou","family":"Diaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Pierre","family":"Sy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Sall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moussa","family":"Seydi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-481X","authenticated-orcid":true,"given":"Geoffrey S.","family":"Gottlieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the University of Washington-Senegal HIV-2 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"issue":"14","key":"pgph.0005743.ref001","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1128\/JVI.79.14.8979-8990.2005","article-title":"The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates","volume":"79","author":"KK Ari\u00ebn","year":"2005","journal-title":"J Virol"},{"issue":"11","key":"pgph.0005743.ref002","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1097\/00002030-199311000-00002","article-title":"Cellular and plasma viral load in patients infected with HIV-2","volume":"7","author":"F Simon","year":"1993","journal-title":"AIDS"},{"issue":"11","key":"pgph.0005743.ref003","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1097\/00002030-199411000-00015","article-title":"HIV-2-infected patients survive longer than HIV-1-infected patients","volume":"8","author":"H Whittle","year":"1994","journal-title":"AIDS"},{"issue":"18","key":"pgph.0005743.ref004","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1097\/00002030-200312050-00006","article-title":"Factors associated with clinical progression in HIV-2 infected-patients: the French ANRS cohort","volume":"17","author":"S Matheron","year":"2003","journal-title":"AIDS"},{"issue":"4761","key":"pgph.0005743.ref005","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1126\/science.2425430","article-title":"Isolation of a new human retrovirus from West African patients with AIDS","volume":"233","author":"F Clavel","year":"1986","journal-title":"Science"},{"issue":"7","key":"pgph.0005743.ref006","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(18)30094-8","article-title":"90-90-90 for HIV-2? 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