Immune activation; allergic drug toxicity and mortality in HIV-positive tuberculosis

ABSTRACT

This study was conducted to correlate serum levels of markers of immune activation with mortality and drug toxicity in HIV+TB. Design: Substudy of a randomised clinical trial of streptomycin-thiacetazone-isoniazid (STH) vs. rifampin-isiniazid-pyrazinamide (RHZ) in HIV + TB. Design: Substudy of a randomized clinical trial of streptomycin-thiacetazone-isoniazid (STH) vs. rifampin-isoniazid-pyrazinamide (RHZ) in HIV + TB. Results: Neopterinor =14 ng/mg; TNF-alpha receptorsor = 6.5 ng/ml; and negative skin test were independently associated with increased mortality (P0.01). Among STH-treated subjects; dermatologic toxicity and mortality (P0.05); although these two adverse events occurred independently. Activation markers increased from baseline after 2 months of therapy with the less rapidly bactericidal STH regimen; whereas they declined in those treated with RHZ; suggesting a relationship with continued mycobacterial replication. Conclusions: Immune activation in HIV+TB is associated with shortened survival and increased risk of drug toxicity. HIV+TB patients with elevated serum neopterin should be treated with a rapidly-bactericidal drug regimen which does not include thiacetazone