Factors Impacting Early Mortality in Tuberculosis/HIV Patients: Differences between Subjects Naïve to and Previously Started on HAART

BACKGROUND Mortality among patients with tuberculosis (TB)/HIV is highest during the first few months of antituberculous therapy. The objective of this study was to assess the factors associated with early mortality among TB/HIV patients and whether these factors are similar for HAART naïve and those with prior HAART initiation. METHODS Prospective cohort study including HIV patients with tuberculosis confirmed by culture, cared for at a referral center in Rio de Janeiro, Brazil. Multivariable Cox analysis was used to assess predictors of mortality within 3 months of antituberculous therapy. RESULTS Among 227 patients included, 90 (40%) started HAART before TB diagnosis. The median time to TB diagnosis after ARV initiation was 5.9 months (interquartile range [IQR] 3.0-8.9 months). Fourteen patients (6%) died within the first 3 months. Mortality was not different between patients previously started on HAART and those who were naïve to it. In the overall adjusted analysis, HAART use during TB treatment (hazard ratio [HR] =0.21, 95% confidential interval [CI] =0.06-0.72) and CD4 lymphocyte count >100 cells/mm3 (HR=0.21, 95% CI=0.04-0.99) were associated with lower mortality, while subjects with unknown baseline CD4 lymphocyte count (HR=9.39, 95% CI=2.56-34.5) had higher mortality. In subgroup analysis, among HAART naïve subjects, disseminated TB (HR=5.32, 95% CI=1.09-25.8) and unknown baseline CD4 lymphocyte count (HR=13.2, 95% CI=2.71-64.5) were associated with significantly higher mortality, while HAART (HR=0.14, 95% CI=0.03-0.69) predicted a better outcome. Among subjects previously started on HAART, mortality was significantly associated with duration of TB symptoms >120 days (HR=6.15, 95% CI=1.15-32.9). CONCLUSIONS Predictors of early mortality among TB/HIV patients may vary according to the timing of HAART initiation. Among HAART naïve patients, mortality was influenced by baseline clinical severity, HAART use and, possibly, the quality of care preceding TB diagnosis. For patients with prior HAART initiation, longer delays in TB diagnosis predicted a significantly higher mortality.