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Low Levels of Clinically Significant Drug Resistance Mutations to Dolutegravir Among Children Living with HIV Failing on First-Line Antiretroviral Therapy in Uganda

Year: 2025

Type: article

Abstract: BACKGROUND: Introduction of pediatric-friendly dolutegravir (DTG) formulations to treat children living with HIV (CLHIV) has presented new opportunities to improve viral suppression; however, there are limited data on emerging patterns of HIV drug resistance (HIVDR) in this population. METHODS: We identified CLHIV aged 0-15 years experiencing virologic failure on first-line antiretroviral therapy in Uganda between January 2021 and November 2021 from the Central Public Health Laboratory database. Remnant viral load samples were tested for HIVDR using Sanger sequencing. Drug resistance mutations (DRMs) were identified, and antiretroviral susceptibility was interpreted using the Stanford University HIVDR Database algorithms. The prevalence of DRMs and HIVDR is summarized using descriptive statistics, and associations with demographic and clinical factors were determined using χ 2 tests. RESULTS: Among 333 successfully genotyped patient samples, 122 (36.6%) CLHIV were on a DTG-based regimen and 136 (40.8%) on a lopinavir-based regimen. Among all CLHIV, 271 (81.4%) had DRMs and 262 (78.7%) had any intermediate-to-high level HIVDR [including DTG (1.8%), lopinavir (9.6%), abacavir (ABC) (25.5%), and zidovudine (19.2%)]. Among CLHIV on a DTG-based regimen, 6.6% had any integrase inhibitor DRMs and 4.1% had intermediate-to-high resistance to DTG. Children on DTG-based regimens were less likely to have DRMs ( P = 0.007) or HIVDR ( P = 0.02) compared with all other regimens. CLHIV on DTG-based regimens with an ABC backbone were no more likely to have DRMs ( P = 0.9) or HIVDR ( P = 0.5) compared with those with a backbone not containing ABC. CONCLUSIONS: Low rates of DTG resistance among Ugandan CLHIV failing first-line DTG-based antiretroviral therapy regimens underscore the durability of DTG. Lack of difference in ABC resistance across all regimens supports maintaining an ABC backbone for CLHIV <30 kg when transitioning to a DTG-based regimen despite virologic failure.

Source: JAIDS Journal of Acquired Immune Deficiency Syndromes

DOI: 10.1097/qai.0000000000003784