Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy Gillian L. Dean a , Simon G. Edwards b , Natalie J. Ives b , Gail Matthews c , Emma F. Fox d , Lesley Navaratne a , Martin Fisher e , Graham P. Taylor f , Rob Miller g , Chris B. Taylor b , Annemiek de Ruiter a and Anton L. Pozniak c Objective: To assess the risks and bene®ts of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. Design and methods: HIV-1 patients presenting to 12 HIV centres in Greater London and south-east England with culture-proven TB were identi®ed from January 1996 to June 1999. Case-notes were reviewed retrospectively. Results: Patients (n  188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 3 10 6 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 signi®cant reductions in viral load, AIDS- de®ning 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 3 10 6 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count , 100 3 10 6 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 ®rst 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. Conclusions: 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 signi®cant 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 3 10 6 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 3 10 6 cells/l). & 2002 Lippincott Williams & Wilkins AIDS 2002, 16:75±83 Keywords: tubercolosis, HIV, adverse events, antiretroviral therapy, CD4, viral load From a St Thomas' Hospital, London, b King's College Hospital, London, the c Chelsea & Westminster Hospital, London, d St George's Hospital, London, the e Royal Sussex County Hospital, Brighton, f St Mary's Hospital, London and g University College Hospital, London, UK. Correspondence to Dr Simon Edwards, Consultant GUM Physician, The Mortimer Market Centre, Off, Capper Street, London WC1E 6AU, UK. Tel: 44 (0)207 530 5055; Fax: 44 (0)207 530 5044; e-mail: simon.edwards@doctors.org.uk Dr Anton Pozniak, Consultant Physician, HIV/GUM, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9TH, UK. Tel: 44 (0)208 746 5620; fax: 44 (0)208 746 5628; e-mail: anton.pozniak@chelwest.nhs.uk Received: 8 December 2000; revised: 13 July 2001; accepted: 23 July 2001. ISSN 0269-9370 & 2002 Lippincott Williams & Wilkins 75