title: Effectiveness of early antiretroviral therapy initiation to improve survival among HIV-infected adults with tuberculosis: a retrospective cohort study.
abstract: BACKGROUND
  Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART) in HIV-infected adults with sputum smear-positive tuberculosis (TB) disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting.
  
  
  RESULTS
  We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count ≤ 350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1) death, default, or lost to follow-up and (2) death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89]) and 0.86 (95% confidence interval: [0.80, 0.92]), respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by unmeasured factors and from model misspecification are small.
  
  
  CONCLUSIONS
  Early cART reduced mortality among individuals with low CD4 counts and improved retention in care, regardless of CD4 count. Please see later in the article for the Editors' Summary.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. molly_franke@hms.harvard.edu
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.forename: James M
authors.initials: JM
authors.lastname: Robins
authors.forename: Jules
authors.initials: J
authors.lastname: Mugabo
authors.forename: Felix
authors.initials: F
authors.lastname: Kaigamba
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Cain
authors.forename: Julia G
authors.initials: JG
authors.lastname: Fleming
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D012432:Rwanda; D016019:Survival Analysis; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents