{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:07:24Z","timestamp":1791223644614,"version":"4.1.0"},"reference-count":15,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Around 2.5 million HIV-infected individuals failing first-line therapy qualify for boosted protease inhibitor (bPI)-based second-line therapy globally. Major resistance mutations are rarely present at treatment failure in patients receiving bPI and the determinants of failure in these patients remain unknown. There is evidence that Gag can impact PI susceptibility. Here, we have sequenced Gag-Protease before and following failure in 23 patients in the SARA trial infected with subtypes A, C, and D viruses. Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I and L63P. Following PI failure, previously described mutations in Protease and Gag were observed, including those at the cleavage sites such as R361K and P453L. However, the emergence of clear genetic determinants of therapy failure across patients was not observed. Larger Gag sequence datasets will be required to comprehensively identify mutational correlates of bPI failure across subtypes.<\/jats:p>","DOI":"10.1089\/aid.2015.0138","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T12:46:16Z","timestamp":1439210776000},"page":"1032-1037","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa"],"prefix":"10.1177","volume":"31","author":[{"given":"Katherine A.","family":"Sutherland","sequence":"first","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth L.","family":"Goodall","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"McCormick","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kapaata","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lyagoba","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontiano","family":"Kaleebu","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geant","family":"Thiltgen","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Gilks","sequence":"additional","affiliation":[{"name":"University of Queensland","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Spyer","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cissy","family":"Kityo","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deenan","family":"Pillay","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]},{"name":"University of KwaZulu Natal","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dunn","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the DART Virology Group and DART Trial Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO: Global Update on the Health Sector Reponse to HIV 2014."},{"key":"e_1_3_3_3_2","unstructured":"WHO: Consolidated guidelines on the use of antiretroviral drugs for treatment and preventing HIV infection 2013."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62067-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2253"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-9-63"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283398216"},{"key":"e_1_3_3_8_2","first-page":"190","article-title":"Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1","volume":"95","author":"Sutherland KA","year":"2014","unstructured":"Sutherland KA, , Mbisa JL, , Cane PA, et al.: Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1. 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