title: The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study.
abstract: BACKGROUND
  Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan.
  
  
  METHODS
  A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test.
  
  
  RESULTS
  There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06-0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16-30 days and at 31-60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01).
  
  
  CONCLUSIONS
  The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31-60 days of TB treatment might be optimal after considering the risks and benefits.
authors.forename: Chin-Hui
authors.initials: CH
authors.lastname: Yang
authors.forename: Kuan-Jung
authors.initials: KJ
authors.lastname: Chen
authors.forename: Jih-Jin
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Lin
authors.forename: Shu-Hsing
authors.initials: SH
authors.lastname: Cheng
authors.forename: Kwei-Feng
authors.initials: KF
authors.lastname: Wang
authors.affiliation: School of Public Health, Taipei Medical University, No, 250, Wu-Hsing Street, Taipei, Taiwan. hychiou@tmu.edu.tw.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013624:Taiwan; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality