{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:27:26Z","timestamp":1787113646294,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Despite Rwanda\u2019s achievement of the UNAIDS 95\u201395\u201395 targets, national evidence on virological failure (VF) and mortality after transition to second- or third-line antiretroviral therapy (ART) remains limited. We estimated the incidence of these outcomes and examined associated factors among people living with HIV (PLWH) transitioned to second- or third-line ART in Rwanda between 2019 and 2025. Methods: We conducted a retrospective cohort study using Rwanda\u2019s national HIV case-based surveillance (CBS) system. PLWH aged \u226515 years who transitioned to second- or third-line ART between 1 January 2019 and 31 December 2025 were followed from transition until the first recorded outcome, last clinical contact, or administrative censoring. The primary operational VF endpoint was the first viral load &gt;1000 copies\/mL recorded \u2265180 days after transition; a prespecified sensitivity analysis required two consecutive measurements &gt;1000 copies\/mL. We used Kaplan\u2013Meier estimation and facility-clustered Cox regression for the composite outcome of VF or death, and Aalen\u2013Johansen cumulative incidence functions and Fine\u2013Gray regression for VF with death treated as a competing event. Results: Among 778 PLWH followed for 3564 person-years (median follow-up, 60.0 months), 81 (10.4%) met the primary operational VF endpoint, and 13 (1.7%) had death recorded as the first event. The composite incidence rate was 2.64 per 100 person-years (95% CI 2.10\u20133.17). In adjusted Cox regression, a PI-based regimen (adjusted hazard ratio [aHR] 2.14, 95% CI 1.37\u20133.36), WHO stage III (aHR 1.92, 95% CI 1.10\u20133.34), and WHO stage IV (aHR 3.59, 95% CI 1.61\u20138.02) were associated with the composite outcome. In Fine\u2013Gray analysis, a PI-based regimen (subdistribution hazard ratio [sHR] 3.37, 95% CI 1.96\u20135.78) and WHO stage IV (sHR 4.44, 95% CI 1.91\u201310.4) were associated with VF. Conclusions: PI-based regimen use and advanced WHO clinical stage were associated with poorer outcomes after ART line transition. These findings support intensified viral load monitoring, adherence and resistance assessment, and individualized regimen review for patients receiving PI-based therapy, together with systematic implementation of the WHO advanced HIV disease package for patients with stage III or IV disease.<\/jats:p>","DOI":"10.3390\/v18080905","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:35:08Z","timestamp":1786984508000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virological Failure and Mortality Among People Living with HIV Transitioned to Second- or Third-Line Antiretroviral Therapy in Rwanda: A Competing-Risks Survival Analysis of National Case-Based Surveillance Data, 2019\u20132025"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1559-6527","authenticated-orcid":false,"given":"Gallican N.","family":"Rwibasira","sequence":"first","affiliation":[{"name":"Rwanda Biomedical Centre, Kigali P.O. Box 7162, Rwanda"},{"name":"Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland"},{"name":"Faculty of Medicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8939-2327","authenticated-orcid":false,"given":"Jean Claude","family":"Kwizera","sequence":"additional","affiliation":[{"name":"Rwanda Biomedical Centre, Kigali P.O. Box 7162, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9929-5739","authenticated-orcid":false,"given":"Tafadzwa","family":"Dzinamarira","sequence":"additional","affiliation":[{"name":"ICAP Global Health, Rwanda Country Office, Kigali P.O. Box 1524, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Karera","sequence":"additional","affiliation":[{"name":"ICAP Global Health, Zambia Country Office, Lusaka P.O. Box 34358, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0813-1793","authenticated-orcid":false,"given":"Gatete","family":"Gaetan","sequence":"additional","affiliation":[{"name":"Rwanda Biomedical Centre, Kigali P.O. Box 7162, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3118-4989","authenticated-orcid":false,"given":"Albert","family":"Tuyishime","sequence":"additional","affiliation":[{"name":"Rwanda Biomedical Centre, Kigali P.O. Box 7162, Rwanda"},{"name":"Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland"},{"name":"Faculty of Medicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Remera","sequence":"additional","affiliation":[{"name":"Rwanda Biomedical Centre, Kigali P.O. Box 7162, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-5987","authenticated-orcid":false,"given":"Daniel Henry","family":"Paris","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland"},{"name":"Faculty of Medicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-9803","authenticated-orcid":false,"given":"Tracy R.","family":"Glass","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland"},{"name":"Faculty of Medicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2025). 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