Prevalence of HIV drug resistance, its correlates and common mutations among people living with HIV failing on ART in northern Uganda. A cross-sectional study.

Background: HIV drug resistance (HIVDR) poses a challenge to managing people living with HIV (PLHIV), particularly among those experiencing virological failure (VF). The West-Nile region of Uganda faces HIV treatment challenges and has a high virological failure rate. We estimated the prevalence of HIV drug resistance, described the HIV drug resistance mutations and evaluated the factors associated with HIVDR among PLHIV with virological failure in the West–Nile region of Uganda. Methods: We conducted a retrospective cross-sectional analysis of HIVDR data in the West-Nile region of Uganda across the 161 health facilities that offer comprehensive Anti–retroviral therapy (ART) services. All PLHIV, regardless of age, who had been on ART for at least one–year, experienced virological failure and underwent an HIVDR test between 1st January 2021 to 30th December 2023 were included in the study. Demographic and clinical data were extracted from the National HIVDR database. HIVDR was defined as having at least one mutation with a penalty score of ≥15. PLHIV were characterized based on age, gender and clinical history. Logistic regression models determined factors associated with HIVDR with a p-value of <0.05 considered significant. Results: A total 295 records were analyzed. Of these , majority were female (56.6%) and adults aged ≥20 years (49.2%). The median age was 19 (Inter quartile range [IQR]: 13–41) years, and median duration on ART was 8 (IQR: 5–10) years. Overall, 218 (73.9%) had HIVDR with 66% of subjects having Non-nucleoside reverse transcriptase (NNRTI) mutations. M184V/I (50%), K103N (34%) and TAMS (26%) were the commonest mutations. Resistance to Etravirine (27%) was higher than that of Dolutegravir (12%) and Darunavir (5%). After accounting for gender, age, Nucleoside reverse transcriptase inhibitor (NRTI) anchor drug, ART regimen type and World Health Organization (WHO) clinical stage of the participants; long duration on ART (aOR=; 1.15 95%CI 1.05 –1.26 p=0.003), adolescents failing on first line (aOR=; 3.80 95%CI 1.02–14.08 p=0.046) and participants failing on 2nd line (aOR=; 3.64 95%CI 1.18–11.21 p=0.024) as indications for the HIVDR test, and the year of HIVDR sample collection (aOR=; 0.21 95%CI 0.07 – 0.69 p=0.010), were independently associated with HIVDR mutations. Conclusion: The study found a high HIVDR prevalence strongly associated with long ART duration which is likely lead to increased ART treatment failure rates. The high Etravirine resistance and increasing Dolutegravir resistance are likely to complicate future treatment options while low Darunavir resistance makes it a future third-line treatment option. Strengthening routine resistance surveillance, timely VL monitoring, and adherence support are critical to mitigating drug resistance and preserving ART effectiveness among PLHIV in the West-Nile region. Keywords: HIV, ART, Viral load, HIVDR, Resistance, Mutations, Uganda.