title: Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy.
abstract: OBJECTIVE
  To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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 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).
authors.affiliation: St Thomas' Hospital, London, UK.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Dean
authors.forename: Simon G
authors.initials: SG
authors.lastname: Edwards
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Ives
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.forename: Emma F
authors.initials: EF
authors.lastname: Fox
authors.forename: Lesley
authors.initials: L
authors.lastname: Navaratne
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Rob
authors.initials: R
authors.lastname: Miller
authors.forename: Chris B
authors.initials: CB
authors.lastname: Taylor
authors.forename: Annemiek
authors.initials: A
authors.lastname: de Ruiter
authors.forename: Anton L
authors.initials: AL
authors.lastname: Pozniak
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004347:Drug Interactions; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D019562:Viral Load
chemical_list: D000995:Antitubercular Agents