Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy

• Published in: AIDS (London) Vol. 16; no. 1; pp. 75 - 83
• Main Authors: DEAN, Gillian L, EDWARDS, Simon G, DE RUITER, Annemiek, POZNIAK, Anton L, IVES, Natalie J, MATTHEWS, Gail, FOX, Emma F, NAVARATNE, Lesley, FISHER, Martin, TAYLOR, Graham P, MILLER, Rob, TAYLOR, Chris B
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 04.01.2002
• Subjects: Adult; Aged; Antiretroviral Therapy, Highly Active - adverse effects; Antitubercular Agents - adverse effects; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Bacterial diseases; Biological and medical sciences; CD4 Lymphocyte Count; Drug Interactions; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - mortality; HIV-1 - physiology; Human bacterial diseases; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - isolation & purification; Treatment Outcome; Tuberculosis - complications; Tuberculosis - drug therapy; Tuberculosis - mortality; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Multidrug-Resistant - complications; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - mortality; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Human; Immunopathology; Drug combination; Prognosis; Toxicity; Treatment efficiency; AIDS; Mycobacterial infection; Immune deficiency; Infection; Chemotherapy; Treatment; Tuberculosis; Viral disease; Bacteriosis; Secondary effect; Antiviral; Antituberculous agent; Antibacterial agent
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200201040-00010

To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. HIV-1 patients presenting to 12 HIV centres in Greater London and south-east England with culture-proven TB were identified from January 1996 to June 1999. Case-notes were reviewed retrospectively. Patients (n = 188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 x 106 cells/l (IQR: 30-180). At presentation, 85% (n = 159) were not taking antiretrovirals. A total of 45% commenced HAART during TB treatment, which was associated with significant reductions in viral load, AIDS-defining illness (ADI) [3.5 versus 24.5%; relative risk (RR) = 0.14] and mortality. Only nine of 91 (10%) patients with a CD4 count > 100 x 106 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count < 100 x 106 cells/l developed this complication. Adverse events (AE) occurred in 99 (54%) of 183 patients, one-third of whom changed or interrupted HIV and/or TB medication. The majority of AE occurred within the first 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. Many physicians delay HAART in patients presenting with TB because of pill burden, drug/drug interactions and toxicity. Although the use of HAART led to significant reductions in viral load, ADI and mortality, co-infected patients commonly experienced AE leading to interruptions in TB/HIV therapy. We therefore recommend starting HAART early for patients with advanced HIV disease (CD4 < 100 x 106 cells/l) and deferring HAART until the continuation phase of TB therapy (i.e. after 2 months) for patients who are clinically stable (CD4 > 100 x 106 cells/l).