Incidence and predictors of virological failure among HIV infected children and adolescents receiving second-line antiretroviral therapy in Uganda, a retrospective study.

BACKGROUND: In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. METHODOLOGY: This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. RESULTS: Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 - 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 - 19 years (HR 3.2, 95% 1.6 - 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 - 3.1), p < 0.01) prior to second-line ART switch. CONCLUSION: Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study.

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era. RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve children infected with HIV were enrolled into clinical care. The overall proportion of LTNP was 6.3% (9.5% in Botswana vs 5.9% in Uganda). The median progression-free survival for the cohort was 6.3 years, although this was lower in Botswana than in Uganda (6.6 vs 8.8 years; P <0.001). At baseline, the adjusted subdistribution hazard ratio (aHRsd) of progression was increased among underweight children (aHRsd 1.42; 95% confidence interval [CI]: 1.32-1.53), enrolled after 2010 (aHRsd 1.32; 95% CI 1.22-1.42), and those from Botswana (aHRsd 2; 95% CI 1.91-2.10). CONCLUSIONS: In our study, the prevalence of pediatric LTNP was lower than that observed among adult populations, but progression-free survival was higher than expected. Underweight, year of enrollment into care, and country of origin are independent predictors of progression among children.