Dynamics of plasma cytokine levels in patients with advanced HIV infection and active tuberculosis: implications for early recognition of patients with poor response to anti-tuberculosis treatment.

Abstract

To examine whether the serial measurement of plasma cytokine levels can assist in the early recognition of AIDS/tuberculosis patients with poor response to anti-tuberculosis treatment. Longitudinal, prospective cohort study. A university hospital, the largest centre for HIV/AIDS patients in Taiwan. Between January 1997 and September 1998, 25 consecutive patients with advanced HIV infection and suspected tuberculosis were enrolled in the study. Plasma samples were obtained on day 1 (baseline), 3, 7 and 14 of anti-tuberculosis treatment and the levels of tumour necrosis factor-alpha (TNF-alpha) were measured. Patients were classified as either responders or non-responders according to the results of assessment of symptoms and follow-up cultures during the sixth and eighth week of anti-tuberculosis treatment. Thirty consecutive HIV-negative tuberculosis patients were also enrolled in the study. The data of a total of 16 AIDS patients (median CD4 cell count 16 x 10(6)/l; 12 responders and four non-responders) and 21 HIV-negative patients (16 responders and five non-responders), whose tuberculosis was culture-proven, were included for analysis. In responders, TNF-alpha levels declined remarkably within the first week of anti-tuberculosis treatment; however, the decline of TNF-alpha levels in non-responders was significantly less [the median ratio of TNF-alpha level on day 7 to that at baseline was 0.32 versus 0.85 (P < 0.001) in AIDS patients; 0.34 versus 0.80 (P = 0.001) in HIV-negative patients). The lack of a > or = 50% reduction in pre-treatment TNF-alpha levels during the first week of treatment was strongly associated with a poor response to anti-tuberculosis treatment (P = 0.001 in AIDS patients; P < 0.001 in HIV-negative patients). Serial measurement of plasma TNF-alpha levels may help to assess the response to anti-tuberculosis treatment in AIDS patients, in spite of very low CD4 cell counts. Failure of TNF-alpha levels to decline by > or = 50 % of pre-treatment levels in the first week of treatment may be an early surrogate marker of a poor response.