Correlates of Dolutegravir Resistance in Low- and Middle-Income Countries: A Combined Analysis of Drug Resistance Surveys in Four Countries

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ID: 320728
2026
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Abstract
Abstract Background Dolutegravir (DTG)-based regimens (DBR) account for >97% of antiretroviral drugs dispensed through President’s Emergency Plan for AIDS Relief. Understanding factors associated with DTG drug resistance (DR) is critical to safeguarding its long-term efficacy. Methods We included adults on DBR from cohorts in Malawi, Mozambique, Uganda and Ukraine (2020-2022) with successful genotypes. DTG DR was defined as Stanford HIV Drug Resistance Database genotypic susceptibility score >15. Logistic regression assessed associations between DTG DR and clinical/sociodemographic factors, reporting odds ratios (ORs) and 95% confidence intervals (CIs). Results Median age was 36.2 years; 59% were female; 89% transitioned to DTG from a prior regimen. In a multivariable analyses including findings from genotype test, male sex (OR 2.02, 95% CI 1.10–3.73), any NRTI resistance (OR 31.17, 95% CI 12.93–75.14), and any NNRTI resistance (OR 2.56, 95% CI 1.12–5.88) were associated with DTG DR. After excluding genotype-derived variables, male sex remained associated with DTG DR (OR 2.13, 95% CI 1.28–3.54), while participants receiving zidovudine-containing backbones had higher odds of DTG DR compared with those receiving tenofovir-containing backbones (OR 5.87, 95% CI 2.45–14.07). Among individuals with DTG DR, G118R was the most frequent major mutation. M184V demonstrated high sensitivity (83%) and specificity (91%) for detecting DTG resistance. Conclusions These findings identify key clinical correlates of DTG resistance, including concurrent NRTI/NNRTI resistance and zidovudine-containing regimens, which may serve as proxies for prior viral non-suppression and help inform more targeted drug resistance testing and regimen optimization in settings where genotypic testing is not readily available.
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Authors Juliana da Silva, Mariama Tejan, Sherri Pals, Newton Kalata, Nellie Wadonda, Clement Zeh, Marianna Azarskova, Mariia Liulchuk, Nália Ismael, Nilesh Bhatt, Gillian Masamha, Christine Watera, Grace Namayanja, Elliot Raizes
Journal Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year 2026
DOI
10.1093/cid/ciag427
URL
https://doi.org/10.1093/cid/ciag427
Keywords Keywords not found

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