Temporal Trends in Co-trimoxazole Use Among Children on Antiretroviral Therapy and the Impact of Co-trimoxazole on Mortality Rates in Children Without Severe Immunodeficiency

Abstract

Abstract Background Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015–2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09–1.28]), lower height-for-age z score (OR, 1.15 for less than −3 vs greater than −2 [95% CI, 1.08–1.22]), anemia (OR, 1.08 [95% CI, 1.02–1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18–1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17–9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77–1.34]). Conclusions Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency.