Emerging HIV-1 Drug Resistance during Persistent Low-Level Viremia is Associated with Elevated Viral loads among Individuals on First-line Antiretroviral Therapy in Uganda

Background Although persistent low-level viremia (PLLV) has been associated with treatment failure, there is limited data about HIV drug resistance (HIVDR) during PLLV among Ugandans living with HIV. This study assessed HIVDR prevalence, patterns and associated factors among individuals on HIV-1 first-line ART who were experiencing PLLV. Methods A cross-sectional study among individuals with PLLV defined by two consecutive detectable viral load results < 1000 copies/mL and whose adherence scores were ≥ 95% over a twelve-month period. At 12 months, plasma samples of 444 eligible individuals on first-line ART were retrieved. HIVDR genotyping was performed on the protease, reverse transcriptase, and integrase regions of the HIV genome, and factors associated with HIVDR were assessed by logistic regression. Results Of the 444 individuals analyzed, only 67 (15.1%) were successfully genotyped. HIVDR prevalence was detected in 62.1% of those genotyped. Based on antiretroviral therapy (ART) drug classes, 56.1% of individuals in this study had HIVDR to NNRTIs, 42.2% to NRTIs, and 1.5% to both INSTIs and PIs. The most prevalent NRTI drug resistance mutations (DRMs) were M184V/I (40.3%) and K65R (14.9%). The NNRTI K103E/N/S and G190A mutations existed among 30% and 19.4% of individuals, respectively. The INSTI mutations N155H and R263K, together with the PI mutation M46I, were detected in < 2% of the population. Having an elevated viral load (VL between 500 and 999 copies/mL) (aOR: 6.4; 95% CI: (1.49–27.89); p = 0.01) and being below 25 years of age (aOR: 0.13; 95% CI (0.02–0.73); p = 0.02) were factors significantly associated with HIVDR during PLLV. Conclusion We report emerging HIVDR among individuals on first-line ART despite persistent low-level viremia and good drug adherence. HIVDR was associated with elevated PLLV (viral load ranges between 500 and 999 copies/mL) and young age. HIVDR genotyping for individuals on first-line ART experiencing elevated PLLV is highly recommended. Low genotyping success rates present a major impediment to HIVDR studies among individuals with PLLV, suggesting a need to adopt robust next-generation platforms for deep sequencing. Also, HIV intervention programs targeted toward the youth may positively impact HIV control.