Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy.
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).
Dean
Gillian L
GL
St Thomas' Hospital, London, UK.
Edwards
Simon G
SG
Ives
Natalie J
NJ
Matthews
Gail
G
Fox
Emma F
EF
Navaratne
Lesley
L
Fisher
Martin
M
Taylor
Graham P
GP
Miller
Rob
R
Taylor
Chris B
CB
de Ruiter
Annemiek
A
Pozniak
Anton L
AL
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
D000995:Antitubercular Agents