DOI: 10.1177/20499361261467152 ISSN: 2049-9361

Prevalence and determinants of dolutegravir resistance among people living with HIV with virologic failure in North-Eastern Uganda: a retrospective cross-sectional study (2022–2024)

Saadick Mugerwa Ssentongo, Hamidah Kakooza Mulungi, Ronald Opito, William Okello, Connie Nait, Ivan Katende, Baker Bakashaba, Bonniface Oryokot

Background:

In 2016, Uganda adopted the WHO HIV drug resistance (HIVDR) monitoring strategy to track treatment outcomes following the introduction of a dolutegravir (DTG) based regimen as first line among people living with HIV (PLHIV). However, despite widespread transition to DTG-based regimens, evidence on acquired DTG resistance and its determinants remains limited.

Objectives:

To determine the prevalence of acquired DTG resistance among PLHIV with virologic failure and identify associated factors in North-Eastern Uganda.

Design:

We conducted a retrospective cross-sectional study from 24 accredited antiretroviral therapy health facilities in North-Eastern Uganda by 28th February 2025.

Methods:

The study included eligible PLHIV on DTG-based regimens with at least 2 viral loads >1000 copies/mL and a documented HIV genotypic resistance testing result between April 2022 and July 2024. Clinical data were extracted from the national drug resistance dashboard and verified against facility electronic medical records. Logistic regression via generalised estimating equations (GEE) was used to identify factors associated with DTG resistance. A p -value < 0.05 was considered statistically significant.

Results:

Of 225 participants, the median age was 19 years (interquartile range: 15–39), and 55.1% ( n  = 124) were male. The prevalence of high-level to intermediate DTG resistance was 18.7% ( n  = 42), with 14.2% ( n  = 32) having high-level resistance to DTG and 4.4% ( n  = 10) intermediate resistance. Most participants were unemployed (60.0%, n  = 135) and had not disclosed their HIV status (74.2%, n  = 167). DTG resistance was associated with presence of nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs) (adjusted odds ratio (aOR); 12.14, 95% confidence interval (CI): 4.14–35.65, p  < 0.001), poor adherence (aOR; 6.19, 95% CI: 2.54–15.11, p  = 0.001), DTG use ⩾ 3 years (aOR; 9.19, 95% CI: 1.60–52.74, p  = 0.013), and alcohol/substance abuse (aOR; 3.94, 95% CI: 1.74–8.91, p  = 0.001).

Conclusion:

Nearly one in five PLHIV with virologic failure exhibited DTG resistance, predominantly high-level. Key associated factors included poor adherence, being on DTG for ⩾3 years, alcohol/substance abuse, and the presence of relevant NRTI DRM. Strengthening family and peer support, integrating substance abuse screening and management in HIV care, and improving adherence may help reduce the risk of DTG resistance. These findings highlight the urgent need for enhanced HIVDR monitoring and tailored interventions to sustain progress toward HIV epidemic control by 2030.

More from our Archive