title: Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries.
abstract: BACKGROUND
  The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.
  
  
  METHODS
  The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.
  
  
  RESULTS
  Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.
  
  
  CONCLUSIONS
  Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.
authors.forename: Julia
authors.initials: J
authors.lastname: del Amo
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Roger
authors.initials: R
authors.lastname: Logan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sterne
authors.forename: Santiago
authors.initials: S
authors.lastname: Pérez-Hoyos
authors.forename: Inma
authors.initials: I
authors.lastname: Jarrín
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Wolf
authors.initials: W
authors.lastname: de Wolf
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Loveleen
authors.initials: L
authors.lastname: Bansi
authors.forename: Amy
authors.initials: A
authors.lastname: Justice
authors.forename: Joseph
authors.initials: J
authors.lastname: Goulet
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Rémonie
authors.initials: R
authors.lastname: Seng
authors.forename: Giota
authors.initials: G
authors.lastname: Toulomi
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Gargalianos
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Sophie
authors.initials: S
authors.lastname: Abgrall
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology* / Q000382:microbiology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D019049:Developed Countries; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000150:complications; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology / Q000382:microbiology; D012367:RNA, Viral / Q000032:analysis; D014376:Tuberculosis / Q000453:epidemiology* / Q000382:microbiology; D014481:United States / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral