title: Prevalent and incident tuberculosis are independent risk factors for mortality among patients accessing antiretroviral therapy in South Africa.
abstract: BACKGROUND
  Patients with prevalent or incident tuberculosis (TB) in antiretroviral treatment (ART) programmes in sub-Saharan Africa have high mortality risk. However, published data are contradictory as to whether TB is a risk factor for mortality that is independent of CD4 cell counts and other patient characteristics.
  
  
  RESULTS
  This observational ART cohort study was based in Cape Town, South Africa. Deaths from all causes were ascertained among patients receiving ART for up to 8 years. TB diagnoses and 4-monthly CD4 cell counts were recorded. Mortality rates were calculated and Poisson regression models were used to calculate incidence rate ratios (IRR) and identify risk factors for mortality. Of 1544 patients starting ART, 464 patients had prevalent TB at baseline and 424 developed incident TB during a median of 5.0 years follow-up. Most TB diagnoses (73.6%) were culture-confirmed. A total of 208 (13.5%) patients died during ART and mortality rates were 8.84 deaths/100 person-years during the first year of ART and decreased to 1.14 deaths/100 person-years after 5 years. In multivariate analyses adjusted for baseline and time-updated risk factors, both prevalent and incident TB were independent risk factors for mortality (IRR 1.7 [95% CI, 1.2-2.3] and 2.7 [95% CI, 1.9-3.8], respectively). Adjusted mortality risks were higher in the first 6 months of ART for those with prevalent TB at baseline (IRR 2.33; 95% CI, 1.5-3.5) and within the 6 months following diagnoses of incident TB (IRR 3.8; 95% CI, 2.6-5.7).
  
  
  CONCLUSIONS
  Prevalent TB at baseline and incident TB during ART were strongly associated with increased mortality risk. This effect was time-dependent, suggesting that TB and mortality are likely to be causally related and that TB is not simply an epiphenomenon among highly immunocompromised patients. Strategies to rapidly diagnose, treat and prevent TB prior to and during ART urgently need to be implemented.
authors: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Ankur
authors: A
authors: Gupta
authors: Robin
authors: R
authors: Wood
authors: Richard
authors: R
authors: Kaplan
authors: Linda-Gail
authors: LG
authors: Bekker
authors: Stephen D
authors: SD
authors: Lawn
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000401:mortality; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents