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Despite widespread adoption of dolutegravir (DTG)-based first-line ART, many people living with HIV (PLWH) remain on PI-based second-line regimens. Data on major PI drug resistance mutations (DRMs) in Zimbabwe remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective cross-sectional study of archived plasma specimens from PLWH with VF (viral load (VL)\u2009\u2265\u20091,000 copies\/mL) receiving PI-based second-line ART in Zimbabwe between January 2021 and June 2025. HIV-1\n                      <jats:italic>protease<\/jats:italic>\n                      and\n                      <jats:italic>reverse transcriptase<\/jats:italic>\n                      regions were Sanger-sequenced, and resistance was interpreted using the Stanford HIV Drug Resistance Database. Factors associated with major PI DRMs were evaluated using multivariable logistic regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 297 participants, 153 (51.5%, 95% confidence interval [CI] 45.8\u201357.2%) harboured major PI DRMs. The most frequent mutations were M46I (22.6%), V82A (19.2%), and I54V (17.2%). NRTI- and NNRTI-associated DRMs were present in 70.4% and 79.5% of participants, respectively, while 47.8% exhibited triple-class resistance. Predicted susceptibility to darunavir\/ritonavir remained high (78.8%), despite resistance to atazanavir\/ritonavir (45.5%) and lopinavir\/ritonavir (50.8%). In multivariable analysis, increasing age (adjusted odds ratio [aOR] 1.04,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), higher VL (aOR 1.55,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.011) and male sex (aOR 1.59,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.044) were independently associated with major PI DRMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Major PI DRMs and multiclass HIVDR were common among PLWH with VF on PI-based second-line ART. Routine VL monitoring and early resistance testing are needed to detect and guide second-line ART failure in Zimbabwe.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-026-03255-6","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:05:36Z","timestamp":1783695936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Major protease inhibitor drug resistance mutations among patients with virological failure on second-line antiretroviral therapy in Zimbabwe: a retrospective cross-sectional study"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-3103","authenticated-orcid":false,"given":"Justin","family":"Mayini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tendai","family":"Washaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justen","family":"Manasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Zumbika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shungu","family":"Munyati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryman","family":"Shoko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Dahlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinie","family":"Kouamou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"3255_CR1","doi-asserted-by":"publisher","DOI":"10.18356\/9789211066135","volume-title":"The Urgency of Now: AIDS at a Crossroads \u2014 Global AIDS Update 2024","author":"UNAIDS","year":"2024","unstructured":"UNAIDS. 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