Predicting mortality in HIV-infected children initiating highly active antiretroviral therapy: A risk scoring system for resource-limited settings
Creators: name: Nugent, James
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Background: Access to highly active antiretroviral therapy (HAART) among HIV-infected children in sub-Saharan Africa is increasing. WHO estimated that 387,500 children were receiving HAART in this region at the end of 2010. Recent studies have demonstrated that children starting HAART in resource-poor countries can achieve similar outcomes to children in resource-rich countries. However, mortality rates remain higher in resource-poor countries, especially during the first six months of therapy. Despite scaled-up HAART programs, no prognostic models predicting risk of death are available for children initiating HAART in resource-limited settings. Current clinical prediction tools for HIV-infected children are derived from pre-HAART data and therefore cannot predict mortality in children on HAART. The purpose of this study was to develop a mortality risk scoring system for HAART-naïve, HIV-infected children beginning therapy in a resource-limited setting. In addition, we have conducted a systematic review of the literature identifying the risk factors associated with early mortality and the causes of early death in children initiating HAART. Methods: Observational data were collected and analyzed from HIV-infected children initiating HAART between December 2004 and April 2012 at Kalembe Lembe Pediatric Hospital and Bomoi Health Care Center in Kinshasa, Democratic Republic of the Congo. Univariate and adjusted Cox proportional hazards models were constructed to assess associations between demographic and clinical characteristics at the time of HAART initiation and mortality. Each variable in the final Cox model received a predictor score. Predictor scores were summed to obtain an overall risk score for each child beginning HAART. The risk scoring system was validated internally using bootstrap resampling techniques. Performance of the final model was measured by Harrell’s C statistic. Results: By April 2012, 1005 children had initiated HAART with 3017.4 child-years of follow-up (median 30.8 months on HAART). One hundred children (10.0%) died at a median of 5.3 months post-HAART initiation, yielding a mortality rate of 3.3 deaths (95% CI: 2.7-4.0) per 100 child-years. The final multivariable model included female gender, anemia, severe malnutrition, presence of HIV symptoms, low total lymphocyte count, and age greater than 5 years. These determinants were highly predictive of mortality (C-statistic=0.81). The discriminative ability of our model was comparable to existing pediatric AIDS survival scores that do not account for HAART (C-statistic=0.84). Conclusions: Mortality risk among children starting HAART in this resource-limited setting can be evaluated using a simple scoring system incorporating several readily available factors. Identifying significant predictors of mortality will help clinicians target modifiable risk factors, like anemia and malnutrition, not addressed by HAART. External validation of this model within pediatric HIV-infected cohorts in other resource-limited settings is needed to confirm its utility in assessing prognosis.