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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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.[1]


  1. A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. Wallis, R.S., Kyambadde, P., Johnson, J.L., Horter, L., Kittle, R., Pohle, M., Ducar, C., Millard, M., Mayanja-Kizza, H., Whalen, C., Okwera, A. AIDS (2004) [Pubmed]
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