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. 2025 Nov 6;12(12):ofaf679.
doi: 10.1093/ofid/ofaf679. eCollection 2025 Dec.

Emergence of Acquired HIV Drug Resistance Among Individuals Receiving Dolutegravir-Based Antiretroviral Therapy in Uganda: A National Laboratory-Based Survey 2023

Juliet Nkugwa Asio  1 , Christine Watera  1 , Grace Namayanja  2 , Juliana de Fatima da Silva  3 , Sherri Pals  3 , Deogratius Ssemwanga  1   4 , Grace Sanyu  1 , Maria Nannyonjo  4 , Usher Kabuga Kaganda  1 , Ronald Busobozi  1 , Hellen Nansumba  5 , Miriam Nabukenya  5 , Alisen Ayitewala  5 , Mina Ssali  6 , Cordelia Katureebe  6 , Eleanor Namusoke Magongo  6 , Hudson Balidawa  6 , Esther Nazziwa  2 , Jonathan Ntale  2 , Elliot Raizes  3 , Du-Ping Zheng  3 , Clement Zeh  3 , Stephanie Hackett  3 , Mary Naluguza  2 , Edward Katongole Mbidde  1 , Pontiano Kaleebu  1   4
Affiliations

Emergence of Acquired HIV Drug Resistance Among Individuals Receiving Dolutegravir-Based Antiretroviral Therapy in Uganda: A National Laboratory-Based Survey 2023

Juliet Nkugwa Asio et al. Open Forum Infect Dis. .

Abstract

Background: As dolutegravir (DTG)-based regimens (DBRs) become more widely used and patients remain on treatment longer, cases of virological failure remain rare. This study presents findings from the second annual round of acquired HIV drug resistance (HIVDR) surveillance in Uganda, among individuals with viral nonsuppression (≥1000 copies/mL) receiving DBRs for ≥9 months. The first round was conducted from February to April 2022.

Methods: This nationally representative cross-sectional survey analyzed randomly selected remnant plasma and dried blood spot specimens collected between April and July 2023 from the Central Public Health Laboratories. Genotyping targeted the integrase, protease, and reverse transcriptase regions of the HIV-1 pol gene, resistance was analyzed using the Stanford HIVDR Database. Weighted HIVDR prevalence and 95% confidence intervals (CIs) were calculated for children (0-14 years) and adults (≥15 years).

Results: Out of 857 specimens tested, 400 (46.7%) were from children and 457 (53.3%) from adults. Median ages were 11 years for children and 36 years for adults. Median time on DBRs was 1.9 years for children and 2.4 years for adults. Five hundred and fifty-nine (65.2%) specimens were successfully genotyped. The prevalence of DTG resistance was 10.1% (95% CI: 6.4%-13.9%) in children and 8.6% (95% CI: 3.9%-13.3%) in adult, higher than the first round with a prevalence of 6.6% (95% CI: 3.5%-9.6%) and 4.4% (95% CI: 0.7%-7.1%), respectively.

Conclusions: The increase in DTG resistance among both children and adults highlights the need to strengthen adherence and enhance early identification of individuals at risk of HIVDR through novel and existing programmatic interventions.

Keywords: CADRE; Uganda; acquired resistance to dolutegravir.

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Conflict of interest statement

Potential conflicts of interest. The authors do not have any conflict of interest relevant to this work. Financial support. This work was supported by the US President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention under the terms of the cooperative agreement, award number 5NU2GGH002132-03. Data availability. The sequence data supporting the findings of this study have been deposited in GenBank, and the accession numbers are PV988491–PV989523. Author contributions. Conceived and designed the study: P. K., J. N. A., C. W., J. d. F. d. S., G. N., D. S., G. S., M. Nan., H. N., M. Nab., U. K. K., R. B., M. S., C. K., E. N. M., H. B., E. N., S. P., E. R.. D. P. Z., C. Z., S. H., M. Nal., and E. K. M. Performed the study: P. K., J. N. A., C. W., G. N., D. S., G. S., M. Nan., U. K. K., R. B., and H. N. Analyzed the data: S. P., J. N. A., C. W., D. S., G. S., M. Nan., and P. K. Wrote the paper: J. N. A., C. W., J. d. F. d. S., G. N., D. S., G. S., M. Nan, H. N., M. Nab., M. S., C. K., E. N. M., H. B., E. N., S. P., E. R., D. P. Z., C. Z., S. H., M. Nal., and P. K.

Figures

Figure 1.
Figure 1.
Enrollment profile of study samples of individuals with nonsuppressed VLs on DBRs.
Figure 2.
Figure 2.
INSTI mutations detected in individuals with nonsuppressed VLs on DBRs.
Figure 3.
Figure 3.
Unweighted levels of INSTI resistance detected in individuals with nonsuppressed VLs on DBRs in 2023 and in 2022. Abbreviations: BIC, bictegravir; CAB, cabotegravir; DTG, dolutegravir; EVG, elvitegravir; RAL, raltegravir.
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