title: A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF), an important inflammatory mediator in tuberculosis, has been implicated in causing accelerated HIV disease progression in HIV-associated tuberculosis. However, TNF blockade, particularly by monoclonal antibody, has been associated with the reactivation of latent Mycobacterium tuberculosis infection by the impairment of mycobacterial immunity. This phase 1 study examined the safety, microbiology, immunology, and virology of TNF blockade using etanercept (soluble TNF receptor, Enbrel) during the initial treatment of HIV-associated tuberculosis.
  
  
  METHODS
  A single-arm trial, with key endpoints compared with historical controls, conducted in Mulago Hospital, Kampala, Uganda.
  
  
  METHODS
  : Sixteen HIV-1-infected patients and 42 CD4-frequency-matched controls with sputum smear-positive tuberculosis and CD4 cell counts > 200 cells/microl.
  
  
  METHODS
  Etanercept 25 mg, eight doses administered subcutaneously twice weekly beginning on day 4 of tuberculosis therapy.
  
  
  METHODS
  Serial examination, radiography, sputum culture, CD4 T-cell counts, plasma log10 HIV-RNA copy numbers.
  
  
  RESULTS
  Trends towards superior responses to tuberculosis treatment were evident in etanercept-treated subjects in body mass, performance score, number of involved lung zones, cavitary closure, and time to sputum culture conversion. Etanercept treatment resulted in a 25% increase in CD4 cells by week 4 (P = 0.1 compared with controls). The change in CD4 cell count was inversely related to the change in serum neopterin, a marker of macrophage activation. There was no effect on plasma HIV RNA.
  
  
  CONCLUSIONS
  Etanercept can be safely administered during the initial treatment of pulmonary tuberculosis. Further studies are warranted to examine the effects of etanercept on T-cell numbers, activation and apoptosis in AIDS and tuberculosis.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. r.wallis@umdnj.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
authors.forename: Peter
authors.initials: P
authors.lastname: Kyambadde
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Libby
authors.initials: L
authors.lastname: Horter
authors.forename: Rodney
authors.initials: R
authors.lastname: Kittle
authors.forename: Monika
authors.initials: M
authors.lastname: Pohle
authors.forename: Constance
authors.initials: C
authors.lastname: Ducar
authors.forename: Monica
authors.initials: M
authors.lastname: Millard
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Christopher
authors.initials: C
authors.lastname: Whalen
authors.forename: Alphonse
authors.initials: A
authors.lastname: Okwera
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D000068800:Etanercept; D005260:Female; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D011859:Radiography; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D013183:Sputum / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D014376:Tuberculosis / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000995:Antitubercular Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept