title: Risk factor analyses for immune reconstitution inflammatory syndrome in a randomized study of early vs. deferred ART during an opportunistic infection.
abstract: BACKGROUND
  Immune reconstitution inflammatory syndrome (IRIS) is reported widely in patients initiating antiretroviral therapy (ART). However, few studies are prospective, and no study has evaluated the impact of the timing of ART when allocated randomly during an acute opportunistic infection (OI).
  
  
  RESULTS
  A5164 randomized 282 subjects with AIDS-related OIs (tuberculosis excluded), to early or deferred ART. IRIS was identified prospectively using pre-defined criteria. We evaluated associations between IRIS and baseline variables in subjects with follow-up on ART using Wilcoxon and Fisher's exact tests, logistic regression, and Cox models with time-varying covariates. Twenty of 262 (7.6%) subjects developed IRIS after a median of 33 days on ART. Subjects with fungal infections (other than pneumocystis) developed IRIS somewhat more frequently (OR = 2.7; 95% CI: 1.02, 7.2; p-value = 0.06 (using Fisher's exact test)). In Cox models, lower baseline and higher on-treatment CD4+ T-cell counts and percentage were associated with IRIS. Additionally, higher baseline and lower on-treatment HIV RNA levels were associated with IRIS. Corticosteroids during OI management and the timing of ART were not associated with the development of IRIS.
  
  
  CONCLUSIONS
  In patients with advanced immunosuppression and non-tuberculous OIs, the presence of a fungal infection, lower CD4+ T-cell counts and higher HIV RNA levels at baseline, and higher CD4+ T-cell counts and lower HIV RNA levels on treatment are associated with IRIS. Early initiation of ART does not increase the incidence of IRIS, and concern about IRIS should not prompt deferral of ART.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00055120.
authors.affiliation: Stanford University, Palo Alto, California, United States of America. pmgrant@stanford.edu
authors.forename: Philip M
authors.initials: PM
authors.lastname: Grant
authors.forename: Lauren
authors.initials: L
authors.lastname: Komarow
authors.forename: Janet
authors.initials: J
authors.lastname: Andersen
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Joseph
authors.initials: J
authors.lastname: Eron
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: William
authors.initials: W
authors.lastname: Powderly
authors.forename: Evelyn
authors.initials: E
authors.lastname: Hogg
authors.forename: Carol
authors.initials: C
authors.lastname: Suckow
authors.forename: Andrew
authors.initials: A
authors.lastname: Zolopa
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006678:HIV / Q000187:drug effects; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000378:metabolism; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral