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

• Published in: Tubercle and lung disease 1996-12, Vol.77 (6), p.516-523
• Main Authors: Wallis, R.S., Helfand, M.S., Whalen, C.C., Johnson, J.L., Mugerwa, R.D., Vjecha, M., Okwera, A., Ellner, J.J.
• Format: Article
• Language: English
• Subjects: Adult; AIDS-Related Opportunistic Infections - complications; Antitubercular Agents - adverse effects; Antitubercular Agents - therapeutic use; beta 2-Microglobulin - analysis; Biopterins - analogs & derivatives; Cohort Studies; Drug Therapy, Combination; Female; HIV-1; human immunodeficiency virus 1; Humans; Male; Multivariate Analysis; Neopterin; Random Allocation; Receptors, Interleukin-2 - blood; Receptors, Tumor Necrosis Factor - blood; Skin Diseases - chemically induced; Survival Analysis; Tuberculin Test; Tuberculosis - complications; Tuberculosis - drug therapy; Tuberculosis - immunology; Tumor Necrosis Factor-alpha - analysis
• ISSN: 0962-8479; 1532-219X
• DOI: 10.1016/S0962-8479(96)90049-0

Setting: Tuberculosis Treatment Center, Kampala, Uganda. Objective: HIV-1 affects outcome in pulmonary tuberculosis (TB). Immune mechanisms triggered by Mycobacterium tuberculosis may lead to increased HIV expression and accelerated disease progression. 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 randomized clinical trial of streptomycin-thiacetazone-isoniazid (STH) vs. rifampinisoniazid-pyrazinamide (RHZ) in HIV+TB. Results: Neopterin ≥ 14 ng/ml, TNF-α receptors ≥ 6.5 ng/ml, and negative skin test were independently associated with increased mortality ( P < 0.01). Among STH-treated subjects, dermatologic toxicity and mortality were respectively 13- and 6.3-fold more likely to occur in subjects with elevated neopterin ( P < 0.05), 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. Cadre: Centre de traitement de la tuberculose à Kampala, Uganda. Objectif: Le virus VIH-1 intervient dans l'évolution de la tuberculose pulmonaire. Les mécanismes immunologiques stimulés par Mycobacterium tuberculosis peuvent entraíner une expression accrue du VIH et une progression accélérée de la maladie due à ce virus. Cette étude a été conduite pour corréler les niveaux sériques des marqueurs d'activation immunitaire avec la mortalité et la toxicité médicamenteuse chez les sujets tuberculeux séropositifs pour le VIH. Schéma: Il s'agit d'une étude complémentaire dans le cadre d'un essai clinique randomisé du traitement de sujets tuberculeux VIH-positifs soit par streptomycine-thiacétazone-isoniazide (STH), soit par rifampicineisoniazide-pyrazinamide (RHZ). Résultats: On note que des taux de néoptérine égaux ou supérieurs à 14 ng/ml, des taux de récepteurs de TNF-α égaux ou supérieurs à 6,5 ng/ml et des tests cutanés négatifs sont associés de manière indèpendante à une mortalité accrue ( P < 0,01). Parmi les sujets traités par STH, la toxicité dermatologique et la mortalité sont respec