Risk Factors Associated with TB in Children Receiving ART in a South African Multicenter HIV Cohort

Abstract

Background: Tuberculosis (TB) in children is a direct consequence of adult TB and is a good marker of current trends in community transmission.  We sought to estimate rates of, and risk factors for, incident TB among HIV-infected children and adolescents receiving antiretroviral treatment (ART) in South Africa. Methods: Prospective cohort analysis of HIV-infected children <18 years old who initiated ART between April 2004 and May 2011 at one of 12 HIV clinics in Gauteng and Mpumalanga provinces. Duration on ART was categorized as 0-5.9 and >6 months. We used log-binomial regression with a Poisson distribution to determine predictors of TB risk for children <5 and for those 5-18 years, separately, controlling for, gender and current predictors of TB (e.g. age, duration on ART, viral load and hemoglobin). For children <5 we also controlled for CD4 percent and weight-for-age Z-score over time. For children 5-18 we also controlled for CD4 count and body mass index over time. Results: During 2,828 person-years of follow-up, 113 TB cases (diagnosis confirmed by sputum microscopy) occurred among 3,329 pediatric ART patients. This corresponded to an overall incidence rate of 4.0 cases/100 person-years (95% CI: 3.3-4.8). The highest incidence rate was observed in the first 6-months on ART (5.9/100 person-years; 95% CI: 4.7-7.4). Log-binomial models for children <5 years and 5-18 years showed all patients had over a 2-fold increase in the risk of TB in the first 6-months on ART compared to >6-months. Children <5 years of age with a detectable viral load (>400 copies/mL) had a 70% increase in the risk of TB compared to those children who achieved viral load suppression (risk ratio (RR): 1.7; 95% CI: 0.8-3.7) and patients with a low hemoglobin (<10 ug/dL) (<5 years – risk ratio (RR): 1.7; 95% CI: 0.6-4.8 and 5-18 years -RR 1.7; 95% CI: 0.8-3.6) were also at increased risk. Amongst children 5-18, those younger in age (5-9.9 vs. >10 years-RR 2.4; 95% CI: 1.0-6.0) and patients with low current CD4 count (<100 vs. >500 – RR 4.6; 95% CI: 1.5-14.2) were at increased risk of TB. Conclusions: Our results show that younger age and poor immunologic response to treatment are associated with increased risk of TB. Patients are also at increased risk of TB in the first 6-months after initiation onto ART, potentially a result of immune reconstitution inflammatory syndrome (IRIS). Early ART initiation and intensified TB screening at ART initiation may help improve treatment outcomes in younger HIV-positive children and adolescents.

Conference: CROI conference 2014, Boston, USA