Adherence to antiretroviral therapy and drug resistance impact evolving viral suppression among a cohort of children and adolescents living with perinatal HIV infection in western Kenya

Abstract

Background We characterize antiretroviral therapy (ART) adherence among children and adolescents living with perinatal HIV (CALWH) and investigate its impact on treatment failure (TF) and drug resistance (DR). Methods We enrolled Kenyan CALWH ≤15 years on NNRTI-based ART and monitored adherence over six months, with monthly, validated questionnaires and continuous MEMs (Medication Event Monitoring Systems) electronic dose monitoring. We assessed associations between TF (viral load (VL) >1,000 copies/mL; local guidelines) at 1 month (Blood Draw 1, BD1) and, for a subset, at 4 months (Blood Draw 2, BD2) and adherence using weighted logistic regression. Sanger genotyping identified reverse transcriptase DR mutations upon TF. Associations between number of mutations and adherence was modelled by weighted Poisson regression. Results Among 692 CALWH (51% female; mean 8.4 years) on ART for mean 2.6 years between 2010−2013, 44% reported non-adherence at baseline. At BD1, 21% (N = 143/464) had TF. Reported non-adherence at enrollment and lower MEMS adherence between enrollment and BD1 were significantly associated with TF at BD1 (respectively, OR=1.25 per 1 unit higher non-adherence, 95% CI = 1.05 to 1.48, and OR=0.69 per 1 unit z-score higher MEMS adherence, 95% CI = 0.50 to 0.95). Among those with TF at BD1, 43% (31/72) had TF at BD2, higher MEMS adherence no longer predicted VL suppression. DR genotyping among those with TF at BD1 found fewer mutations for those without treatment interruption >48 hours (RR = 0.17, CI = 0.05 to 0.61), but among them, more mutations for those with longer interruptions (hours, log-10 RR = 2.48, CI = 1.10 to 5.59). More resistance was also associated with longer ART years (Log-10 RR = 1.47, CI = 1.15 to 1.89), and higher log-10 VL at BD1 (RR = 1.21, CI = 1.06 to 1.37)). MEMS adherence had significant, U-shaped relationship, with most mutations at lower (<50%) adherence. Conclusion Well characterized non-adherence among Kenyan CALWH was common and resulted in increased risks for TF and extensive DR, highlighting treatment challenges.