High frequency of HIV-1 drug resistance among individuals with persistent low-level viremia during 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 antiretroviral therapy (ART) who were experiencing PLLV. METHODS: A cross-sectional study among individuals with PLLV defined by two consecutive detectable viral load (VL) results < 1000 copies/mL and whose adherence scores were ≥ 95% over a twelve-month period. At 12 months, plasma samples of 444 individuals with PLLV during 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, 67 (15.1%) were successfully genotyped. HIVDR prevalence was detected in 42/67 (62.7%) of those genotyped. NNRTI mutations existed in 38/67 (56.7%), 29/67 (43.3%) had NRTI mutations while 26/67 (38.8%) had dual class (both NNRTI and NRTI) mutations. The most prevalent NRTI drug resistance mutations (DRMs) were M184V (35.8%) and K65R (14.9%). The most prevalent NNRTI DRMs were K103N (28.4%), G190A (23.9%) and Y181C (9.0%). The prevalence of INSTI mutations (1.5%) was the same as that of PI mutations. Having a 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 a high frequency of HIVDR among individuals on first-line ART despite persistent low-level viremia and good drug adherence. HIVDR among individuals with PLLV was associated with a VL of 500 to 999 copies/mL and young age of below 25 years. HIVDR genotyping for individuals on first-line ART experiencing detectable 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.