Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS

• Published in: American journal of respiratory and critical care medicine 1998-07, Vol.158 (1), p.157-161
• Main Authors: NARITA, M, ASHKIN, D, HOLLENDER, E. S, PITCHENIK, A. E
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - drug therapy; Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Biological and medical sciences; CD4 Antigens; Cell Count; Disease Progression; Drug toxicity and drugs side effects treatment; Human immunodeficiency virus; Humans; Immunosuppression; Medical sciences; Middle Aged; Mycobacterium tuberculosis; Pharmacology. Drug treatments; Toxicity: respiratory system, ent, stomatology; Tuberculin Test; Tuberculosis, Pulmonary - complications; Tuberculosis, Pulmonary - physiopathology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.158.1.9712001

Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.