title: Timing of Antiretroviral Treatment, Immunovirologic Status, and TB Risk: Implications for Testing and Treatment.
abstract: BACKGROUND
  Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4 counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure.
  
  
  METHODS
  We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated.
  
  
  RESULTS
  Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively.
  
  
  CONCLUSIONS
  TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4 count and VLs. These findings suggest that short-term TB risk may be related to low CD4 counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.
authors.affiliation: *Department of Medicine, Division of Infectious Diseases, Vanderbilt University, Nashville, TN; †Vanderbilt University Tuberculosis Center, Department of Medicine, Division of Infectious Diseases and Vanderbilt Institute for Global Health, Nashville, TN; ‡Johns Hopkins University, Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD; §Department of Biostatistics, Vanderbilt University, Nashville, TN; ‖Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC; ¶Department of Medicine, University of Calgary, Calgary, AB, Canada; #Ontario Treatment Network, University of Toronto, Toronto, ON, Canada; and **Department of Medicine, Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD.
authors.forename: April C
authors.initials: AC
authors.lastname: Pettit
authors.forename: Adell
authors.initials: A
authors.lastname: Mendes
authors.forename: Cathy
authors.initials: C
authors.lastname: Jenkins
authors.forename: Sonia
authors.initials: S
authors.lastname: Napravnik
authors.forename: Aimee
authors.initials: A
authors.lastname: Freeman
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: David
authors.initials: D
authors.lastname: Dowdy
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000150:complications / Q000276:immunology*; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology* / Q000821:virology; D009656:North America; D013997:Time Factors; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology; D019562:Viral Load / Q000187:drug effects*