HIV-1 Treatment Failure, Drug Resistance and Clinical Outcomes in Perinatally-Infected Children and Adolescents Failing 1st-Line Antiretroviral Therapy in Western Kenya.

BACKGROUND Long-term impact of drug resistance in perinatally-infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing 1st-line NNRTI-based ART. SETTING Academic Model Providing Access to Healthcare; western Kenya. METHODS Participants were enrolled in 2010-13 (timepoint-1) and a subsample re-enrolled after 4-7 years (timepoint-2). Viral load was performed on timepoint-1 samples, with genotyping of those with detectable viral load. Primary endpoints were treatment failure (viral load>1,000 copies/mL) at and death before timepoint-2. Multinomial regression analysis was used to characterize resistance effect on death, failure and loss-to-follow-up, adjusting for key variables. RESULTS The initial cohort (n=480) was 52% (n=251) female, median age eight years, median CD4% 31, 79% (n=379) on zidovudine/abacavir+lamivudine+efavirenz/nevirapine for median two years. Of these, 31% (n=149) failed at timepoint-1. Genotypes at timepoint-1, available on n=128, demonstrated 93% (n=119) extensive resistance, impacting 2nd-line. Of 128, 22 failed at timepoint-2, 17 died and 32 were lost-to-follow-up before timepoint-2. Having ≥5 resistance mutations at timepoint-1 was associated with higher mortality (relative risk ratio=8.7, confidence interval 2.1-36.3) and loss-to-follow-up (relative risk ratio=3.2, confidence interval 1.1-9.2). Switching to 2nd-line was associated with lower mortality (relative risk ratio<0.05, confidence interval <0.05-0.1) and loss-to-follow-up (relative risk ratio=0.1, confidence interval <0.05-0.3). CONCLUSION Extensive resistance and limited switch to 2nd-line in perinatally-infected Kenyan CALWH failing 1st-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.