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

Abstract

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).