Browsing by Author "Buleya S"

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    Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.
    (2025-Feb-05) Skrivankova VW; Huwa J; Muula G; Chiwaya GD; Banda E; Buleya S; Chihota B; Chintedza J; Bolton C; Tweya H; Kalua T; Hossmann S; Kouyos R; Wandeler G; Egger M; Lessells RJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Diabetes Center Berne, Bern, Switzerland.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.; Lighthouse Trust, Lilongwe, Malawi.; Centre for Infectious Disease Epidemiology and Research, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Center for International Health, Education, and Biosecurity (Ciheb) at University of Maryland, Baltimore School of Medicine (UMB), Lilongwe, Malawi.; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; International Training and Education Center for Health (I-TECH), Lilongwe, Malawi.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).