title: Post-treatment effect of isoniazid preventive therapy on tuberculosis incidence in HIV-infected individuals on antiretroviral therapy.
abstract: In HIV-uninfected individuals, isoniazid preventive therapy (IPT) has been associated with long-term protection against tuberculosis (TB). For HIV-infected/antiretroviral therapy (ART)-naive individuals, high TB rates have been observed following completion of IPT, consistent with a lack of 'cure' of infection. Recent trial data of IPT among HIV-infected individuals on ART in Khayelitsha, South Africa, have suggested that the effect of IPT persisted following completion of IPT.
  
  
  
  Using mathematical modelling, we explored if this increased duration of protection may be due to an increased curative ability of IPT when given in combination with ART. The model was used to estimate the annual risk of infection and proportion of individuals whose latent infection was 'cured' by IPT, defined such that they must be reinfected to be at risk of disease.
  
  
  
  The estimated annual risk of infection was 4.0% (2.6-5.8) and the estimated proportion of individuals whose latent Mycobacterium tuberculosis infection was cured following IPT was 35.4% (2.4-76.4), higher than that previously estimated for HIV-infected/ART-naive individuals. Our results suggest that IPT can cure latent M. tuberculosis infection in approximately one-third of HIV-infected individuals on ART and therefore provide protection beyond the period of treatment.
  
  
  
  Among HIV-infected individuals on ART in low incidence settings, 12 months of IPT may provide additional long-term benefit. Among HIV-infected individuals on ART in high incidence settings, the durability of this protection will be limited because of continued risk of reinfection, and continuous preventive therapy together with improved infection control efforts will be required to provide long-term protection against TB.
authors.affiliation: aDepartment of Infectious Disease Epidemiology, TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine bDepartment of Infection and Population Health, Centre for Infectious Disease Epidemiology, University College London, London, UK cDepartment of Medicine, Institute of Infectious Disease and Molecular Medicine, University of Cape Town dDivision of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa eTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA fCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa gDepartment of Medicine, Imperial College London hThe Francis Crick Institute Mill Hill Laboratory, London, UK iInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Tom
authors.initials: T
authors.lastname: Sumner
authors.forename: Rein M G J
authors.initials: RM
authors.lastname: Houben
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Richard G
authors.initials: RG
authors.lastname: White
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000008:administration & dosage*; D008962:Models, Theoretical; D013019:South Africa; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000453:epidemiology* / Q000517:prevention & control*
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D007538:Isoniazid