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.

A prospective cohort study of outcomes for isoniazid prevention therapy: a nested study from a national QI collaborative in Uganda.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019. METHODS: This was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer-Lemeshow tests. RESULTS: The completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects. CONCLUSION: Treatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.