AEGiS-CATIE: Drug absorption--implications for TB and protease inhibitors

Drug absorption--implications for TB and protease inhibitors

TreatmentUpdate83 - Vol. 9, No. 9 - pp. 5; November 1997
Sean Hosein

Researchers have reported that absorption of anti-TB drugs may be reduced in PHAs. Doctors in Canada recently published their work on this, confirming the problem. Malabsorption of drugs seems to occur even in PHAs who are symptom-free and is worse in PHAs with symptoms of HIV infection. The Canadian research is important because it may draw attention to a similar issue in another area--protease inhibitors.

Study details

Doctors recruited 48 volunteers (4 female, 44 male) for this study, none of whom had TB. Subjects were divided into 4 groups:

* Group I - healthy, non-HIV-infected subjects

* Group II - HIV-infected but symptom-free

* Group III - HIV-infected with symptoms

* Group IV - HIV-infected with symptoms including persistent diarrhea.

Subjects received 3 different TB medications orally

* isoniazid 300 mg

* ethambutol 1,000 mg

* rifampin 600 mg

* pyrazinamide 1,000 mg.

The drugs were taken together "each morning for 4 days." Technicians took blood samples regularly for analyses. Not surprisingly, CD4+ cell counts in group II were greater than in group III, which in turn were greater than in group IV.

Results

The researchers found that, in general, there was 32% less rifampin and 24% less pyrazinamide in the blood of PHAs compared to non-PHAs. This was statistically significant; that is, not likely due to chance alone. Overall, absorption decreased as the immune system weakened.

Should doses be increased?

Although absorption of two critical drugs was decreased, the study doctors do not yet recommend increased doses of anti-TB drugs for PHAs. This is because the level of drugs in the blood of volunteers was still high enough to have anti-bacterial activity. Most TB-causing bacteria, however, are in the tissues, not in the blood. Another reason for not increasing the dose of anti-TB medications is that studies need to be done on PHAs with active TB to see if dose adjustments are necessary.

Protease Inhibitors

Malabsorption of TB drugs has been linked to persistent fever in "an HIV-negative man being treated for [TB]." As well, it has also been the cause of less-than normal levels of anti-TB drugs in the blood which may lead to the development of resistance. Similarly, in PHAs who use protease inhibitors, malabsorption may lead to the development of resistance, even if the drugs are taken according to schedule and at the recommended dose. If lab tests are available, doctors may wish to monitor the levels of these drugs in the blood of their patients, adjusting the dose if necessary.

REFERENCES:

1. Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Annals of Internal Medicine 1997;127:289-293.

971101
CATE8307

ÆGIS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., the National Library of Medicine, and donations from users l This article first appeard in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca

Disclaimer: The editors have taken all such care as they consider reasonable in preparing this database, but they cannot be held responsible for any inaccuracies or mis-statements of fact contained herein. Inclusion in this database of any information on any treatment, therapy, or clinical trial in no way represents an endorsement of that treatment, therapy, or trial by ÆGiS or any of its sponsors. This data should always be used in conjunction with professional medical advice.
©1997. ÆGiS.