title: Isoniazid preventive therapy, HAART and   tuberculosis risk in HIV-infected adults in South   Africa: a prospective cohort.
abstract: BACKGROUND
  The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa.
  
  
  METHODS
  Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk.
  
  
  RESULTS
  Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR)=6.2/100 person-years; 95% CI 5.5-7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2-8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4-6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4-7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02-7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR)=0.36; 95% CI 0.25-0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR=0.11; 95% CI 0.02-0.78).
  
  
  CONCLUSIONS
  Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.
authors.affiliation: Johns Hopkins University, School of Medicine, 1550 Orleans St., 1M.07 Baltimore, MD 21231, USA. jgolub@jhmi.edu
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Golub
authors.forename: Paul
authors.initials: P
authors.lastname: Pronyk
authors.forename: Lerato
authors.initials: L
authors.lastname: Mohapi
authors.forename: Nkeko
authors.initials: N
authors.lastname: Thsabangu
authors.forename: Mosa
authors.initials: M
authors.lastname: Moshabela
authors.forename: Helen
authors.initials: H
authors.lastname: Struthers
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.forename: James A
authors.initials: JA
authors.lastname: McIntyre
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D007538:Isoniazid