title: Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging.
  
  
  OBJECTIVE
  To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB.
  
  
  METHODS
  PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015).
  
  
  METHODS
  Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment).
  
  
  METHODS
  Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS).
  
  
  RESULTS
  The 8 included trials (n = 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2 = 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050 × 109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2 = 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050 × 109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2 = 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2 = 19%).
  
  
  CONCLUSIONS
  Few trials provided sufficient data for subgroup analysis.
  
  
  CONCLUSIONS
  Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050 × 109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050 × 109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation.
  
  
  BACKGROUND
  None. (PROSPERO registration: CRD42012001884).
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.forename: Charles
authors.initials: C
authors.lastname: Okwundu
authors.forename: Kayode
authors.initials: K
authors.lastname: Gbenga
authors.forename: Jimmy
authors.initials: J
authors.lastname: Volmink
authors.forename: David
authors.initials: D
authors.lastname: Dowdy
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Jean B
authors.initials: JB
authors.lastname: Nachega
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D060085:Coinfection; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology; D008297:Male; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D019380:Anti-HIV Agents