A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis

AIDS. 2004 Jan 23;18(2):257-64. doi: 10.1097/00002030-200401230-00015.


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.

Design: A single-arm trial, with key endpoints compared with historical controls, conducted in Mulago Hospital, Kampala, Uganda.

Subjects: : Sixteen HIV-1-infected patients and 42 CD4-frequency-matched controls with sputum smear-positive tuberculosis and CD4 cell counts > 200 cells/microl.

Intervention: Etanercept 25 mg, eight doses administered subcutaneously twice weekly beginning on day 4 of tuberculosis therapy.

Main outcome measures: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / drug therapy*
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • CD4 Lymphocyte Count
  • Etanercept
  • Female
  • HIV-1*
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / adverse effects
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / isolation & purification
  • Radiography
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Sputum / chemistry
  • Sputum / cytology
  • Sputum / microbiology
  • Tuberculosis / complications
  • Tuberculosis / diagnostic imaging
  • Tuberculosis / drug therapy*


  • Adjuvants, Immunologic
  • Antitubercular Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Etanercept