Get started
Work

Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.

Year: 2025
Type: article
Abstract: 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).
DOI: 10.48350/197686
Authors: Whitesell, Veronika, Huwa, Jacqueline, Muula, Guy, Chiwaya, Geldert D, Banda, Esau, Buleya, Shameem, Chihota, Belinda, Chintedza, Joseph, Bolton, Carolyn, Tweya, Hannock, Kalua, Thokozani, Hossmann, Stefanie, Kouyos, Roger, Wandeler, Gilles, Egger, Matthias, Lessells, Richard J
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W6910531890
FWCI:
Cites:
Cited by:
Related to: