Confirmed virological failure following enhanced adherence counseling among virally unsuppressed children and adolescents on dolutegravir-based versus other regimens: Evidence from a cohort analysis in Cameroon

Abstract

Achieving and maintaining viral suppression (VS) in pediatric populations remain suboptimal in low- and middle-income countries (LMICs), calling for the optimized management approaches. We compared the rate of confirmed virological failure (cVF) and associated factors among virally non-suppressed (VnS) children and adolescents after enhanced adherence counseling (EAC) on dolutegravir-based versus other regimens. A multicentre and prospective cohort study was conducted among ART-experienced children (<10 years) and adolescents (10-19 years) with VnS followed-up for confirmatory viral load (VL) after EAC. cVF was defined as 2 consecutive VL ≥ 1000 copies/mL after ≥6 months of ART and EAC. Overall, 250 individuals with VnS were enrolled, median [IQR] age was 12 (11-13) and median duration on ART was 57 (48-67) months. According to ART-regimens, 48.4% received DTG-based regimens (TDF/3TC/DTG: 32.8%; ABC/3TC + DTG: 15.6%). Overall, cVF rate was 39.2% (95% CI: 33.3-45.3), with a longer duration on ART among cVF-group (68 [60-79] months) versus VS-group (48 [45-61]), P = .026. According to ART-regimen, cVF rate was 29.3% in those receiving TDF/3TC/DTG versus 43.5% for ABC/3TC + ATV/r/LPV/r and 25.6% for ABC/3TC + DTG, P = .007. Regarding anchor-drugs, cVF with DTG, EFV and ATV/r/LPV/r was 28.1%, 48.4% and 49.2%, respectively, P = .007. Interestingly, 13.2% of participants with VS had detectable low-level viremia (400-999 copies/mL), with 5.8%, 7.7% and 12.9% being observed in those receiving DTG, ATV/r/LPV/r, and EFV/NVP-based regimen, respectively, P = .013. Only anchor-drug was found to be a predictor of cVF. Compared to those receiving DTG-based regimens, ART based on ATV/LPV/r (aOR [95% CI]: 0.298 [0.132-0.72], P = .004) or EFV/NVP (aOR [95% CI]: 0.401 [0.163-0.983], P = .046) was significantly less likely to achieve VS. About 40% of Cameroonian children/adolescents with VnS experience cVF, which is indicative that EAC significantly contributes to viral re-suppression (60%), especially with DTG-based regimens. Thus, implementing a strategy that couples DTG-transition with EAC-interventions would contribute substantially to efforts in eliminating pediatric AIDS in LMICs.