Barriers to viral suppression in children aged 9 years or younger on dolutegravir-based antiretroviral therapy in Malawi, a mixed-methods study.

After the transition to pediatric dolutegravir-based regimens, viral load (VL) suppression among children with HIV (CWH) in Malawi has remained suboptimal. This mixed-methods study assessed factors associated with high VL among young CWH on dolutegravir-based antiretroviral therapy (ART) and explored adherence barriers from primary-caregiver and healthcare worker perspectives. Between April-July 2023, we performed an unmatched case-control study at 49 Malawian health facilities. We included CWH aged ≤9 years, on dolutegravir-based ART, with a routine VL test-result that was high (≥1,000 copies/mL) for cases, or suppressed (<200 copies/mL) for controls. Using mixed-effect modified Poisson regression, we determined factors associated with high VL, adjusting for sex, site and district. To assess adherence barriers, we conducted in-depth interviews (IDIs) with randomly selected caregivers of CWH with high VL and with healthcare workers providing pediatric HIV care. Data were analyzed using a hybrid thematic approach that combined deductive and inductive coding strategies. We enrolled 538 CWH: 222 cases, with high VL and 316 controls, with suppressed VL. Duration on ART > 4 years (aRR = 0.86, 95% CI: 0.77-0.95) and ≥2 interruption in treatment episodes (≥28 days late for clinic appointment) in the 12 months before VL sample collection (aRR = 1.47, 95% CI: 1.28-1.68) were significantly associated with high VL. Through 54 IDIs (30-caregivers, 24-healthcare workers), five key adherence challenges were identified and affected the children ≤5 years the most: resistance to daily medication, difficulties taking multiple pills, food insecurity, fear of unintentional disclosure, and inability to attend clinic appointments consistently. This study highlights that behavioral, socio-economic and psychosocial factors influences ART adherence among CWH. Duration on ART and recent interruptions in treatment were associated with high VL, stressing the need for targeted interventions that will require health-system and client-level approaches to improve VL suppression among CWH in Malawi and similar settings.