Emerging Dolutegravir Resistance Among Children on Antiretroviral Therapy With Virological Failure in Malawi: Results From a 2023 National Cross-Sectional Survey.

Abstract

Introduction: Malawi began transitioning children living with HIV (CLHIV) to dolutegravir-based regimens (DBRs) in 2020, and 99.9% were on a DBR by September 2023. With nearly universal use of DBR, surveillance of HIV drug resistance (HIVDR) to dolutegravir is essential. We describe the prevalence and patterns of HIVDR among CLHIV on DBR with confirmed virological failure (viral load [VL] twice ≥1000 copies/mL).

Methods: We randomly selected 19 of the 25 highest-volume ART health facilities in Malawi for participant enrolment between July 2022 and February 2023. Enrolment criteria included CLHIV aged 2-14 years, on a DBR for ≥9 months and VL ≥1000 copies/mL. Sanger HIVDR genotyping was performed if a repeat VL result post-intensive adherence counselling was ≥1000 copies/mL. The Stanford University HIVDR Database was used for drug resistance interpretation. We present weighted HIVDR prevalence estimates with 95% confidence limits accounting for correlation within clinics.

Results: Of 302 CLHIV enrolled, 133 (44%) had confirmed virological failure. The weighted prevalence of dolutegravir resistance among CLHIV with confirmed virological failure was 15.6% (95% CI: 7.1-24.0%), with the presence of major dolutegravir drug resistance mutations (DRMs) in 14.2% (95% CI: 4.8-23.6). The most common dolutegravir DRMs were R263K (n = 11) and G118R (n = 4). Weighted prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors were 42.2%, 65.5% and 5.0%, respectively. Three children had HIVDR to all four drug classes.

Conclusions: Dolutegravir resistance was found in nearly one in six Malawian CLHIV with confirmed virological failure on DBRs. This raises concerns for treatment options in this vulnerable population, given the coexistence of high prevalence of resistance to NRTIs and NNRTIs. These results point to the need for regular HIVDR surveillance and further research to guide genotyping prioritization and next-line treatment strategies.