title: Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team.
abstract: BACKGROUND
  Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain.
  
  
  OBJECTIVE
  To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  29 university-based clinical centers in the United States.
  
  
  METHODS
  643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy.
  
  
  METHODS
  Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322).
  
  
  METHODS
  Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals.
  
  
  RESULTS
  During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]).
  
  
  CONCLUSIONS
  Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.
authors.affiliation: University of California, Los Angeles, CARE Center, 10833 LeConte Avenue, Room BH-412 CHS, Los Angeles, CA 90095, USA. jscurrier@mednet.ucla.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Currier
authors.forename: P L
authors.initials: PL
authors.lastname: Williams
authors.forename: S L
authors.initials: SL
authors.lastname: Koletar
authors.forename: S E
authors.initials: SE
authors.lastname: Cohn
authors.forename: R L
authors.initials: RL
authors.lastname: Murphy
authors.forename: A E
authors.initials: AE
authors.lastname: Heald
authors.forename: R
authors.initials: R
authors.lastname: Hafner
authors.forename: E L
authors.initials: EL
authors.lastname: Bassily
authors.forename: H M
authors.initials: HM
authors.lastname: Lederman
authors.forename: C
authors.initials: C
authors.lastname: Knirsch
authors.forename: C A
authors.initials: CA
authors.lastname: Benson
authors.forename: H
authors.initials: H
authors.lastname: Valdez
authors.forename: J A
authors.initials: JA
authors.lastname: Aberg
authors.forename: J A
authors.initials: JA
authors.lastname: McCutchan
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000517:prevention & control*; D010919:Placebos; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D010919:Placebos; D012367:RNA, Viral; D017963:Azithromycin