title: Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in sub-Saharan Africa.
abstract: 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.
  
  
  RESULTS
  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/mm(3) (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/100 pyar [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/mm(3) (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/mm(3) [IQR; 107, 258, n = 118] vs 209 cells/mm(3) [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 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 immunological failure definitions.
  
  
  CONCLUSIONS
  Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. shermans@idi.co.ug
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hermans
authors.forename: Agnes N
authors.initials: AN
authors.lastname: Kiragga
authors.forename: Petra
authors.initials: P
authors.lastname: Schaefer
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
mesh_terms: D000328:Adult; D000554:Ambulatory Care Facilities; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology* / Q000209:etiology*; D014454:Uganda / Q000453:epidemiology; D014505:Urban Population / Q000706:statistics & numerical data