title: Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome.
abstract: OBJECTIVE
  We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks.
  
  
  METHODS
  HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS.
  
  
  RESULTS
  The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm(3) and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS.
  
  
  CONCLUSIONS
  In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation.
authors.affiliation: Epicentre, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Epicentre, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Baudin
authors.affiliation: Instituto Nacional de Saúde, Maputo, Mozambique.
authors.forename: Ilesh V
authors.initials: IV
authors.lastname: Jani
authors.affiliation: Hospital Central, Maputo, Mozambique.
authors.forename: Elizabete
authors.initials: E
authors.lastname: Nunes
authors.affiliation: Médecins sans Frontières, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Verhoustraten
authors.affiliation: Geneva University Hospital, Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Hospital Central, Maputo, Mozambique.
authors.forename: Rui
authors.initials: R
authors.lastname: Bastos
authors.affiliation: Instituto Nacional de Saúde, Maputo, Mozambique.
authors.forename: Nilesh B
authors.initials: NB
authors.lastname: Bhatt
authors.affiliation: Annecy Hospital, Annecy, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Michon
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000453:epidemiology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000453:epidemiology*; D015994:Incidence; D009026:Mortality; D009073:Mozambique / Q000453:epidemiology; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D014376:Tuberculosis / Q000453:epidemiology*
chemical_list: D044966:Anti-Retroviral Agents