Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in Sub-Saharan Africa

Background: Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda. Methodology/Principal Findings: Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm³ (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm³ (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm³ [IQR; 107, 258, n = 118] vs 209 cells/mm³ [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm³: 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm³: 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunogical failure definitions. Conclusions/Significance: Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm³. Incident TB during ART is associated with long-term impairment in immune recovery.