title: Earlier initiation of antiretroviral therapy, increased tuberculosis case finding and reduced mortality in a setting of improved HIV care: a retrospective cohort study.
abstract: OBJECTIVE
  High early mortality after antiretroviral therapy (ART) initiation in resource-limited settings is associated with low baseline CD4 cell counts and a high burden of opportunistic infections. Our large urban HIV clinic in Uganda has made concerted efforts to initiate ART at higher CD4 cell counts and to improve diagnosis and care of patients coinfected with tuberculosis (TB). We sought to determine associated treatment outcomes.
  
  
  METHODS
  Routinely collected data for all patients who initiated ART from 2005 to 2009 were analysed. Median baseline CD4 cell counts by year of ART initiation were compared using the Cuzick test for trend. Mortality and TB incidence rates in the first year of ART were computed. Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models.
  
  
  RESULTS
  First-line ART was initiated in 7659 patients; 64% were women, and the mean age was 37 years (standard deviation 9 years). Median baseline CD4 counts increased from 2005 to 2009 [82 cells/μL (interquartile range (IQR) 24, 153) to 148 cells/μL (IQR 61, 197), respectively; P<0.001]. The mortality rate fell from 6.5/100 person-years at risk (PYAR) [95% confidence interval (CI) 5.5-7.6 PYAR] to 3.6/100 PYAR (95% CI 2.2-5.8 PYAR). TB incidence rates increased from 8.2/100 PYAR (95% CI 7.1-9.5 PYAR) to 15.6/100 PYAR (95% CI 12.4-19.7 PYAR). A later year of ART initiation was independently associated with decreased mortality (HR 0.91; 95% CI 0.83-1.00; P=0.04).
  
  
  CONCLUSIONS
  Baseline CD4 cell counts have increased over time and are associated with decreased mortality. Additional reductions in mortality might be a result of a better standard of care and increased TB case finding. Further efforts to initiate ART earlier should be prioritized even in a setting of capped or reduced funding for ART programmes.
authors.affiliation: Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda. shermans@idi.co.ug
authors.forename: S M
authors.initials: SM
authors.lastname: Hermans
authors.forename: F
authors.initials: F
authors.lastname: van Leth
authors.forename: Y C
authors.initials: YC
authors.lastname: Manabe
authors.forename: A I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: J M A
authors.initials: JM
authors.lastname: Lange
authors.forename: A
authors.initials: A
authors.lastname: Kambugu
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012189:Retrospective Studies; D014376:Tuberculosis / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D014454:Uganda / Q000453:epidemiology; D014505:Urban Population / Q000706:statistics & numerical data
chemical_list: D019380:Anti-HIV Agents