AIDS TREATMENT NEWS Issue #180, August 6, 1993
John S. James
Unfortunately, adverse reactions to TMP-SMX occur in over half of HIV-infected patients, which often prevents use of this drug. Sometimes aerosolized pentamidine is used as an alternative, but this medication is much less effective than TMP-SMX as pneumocystis prophylaxis, and is not effective in preventing toxoplasmosis, or pneumocystis outside the lungs.
It is unclear why persons with HIV have a much higher rate of reaction to TMP-SMX than those in the general population. One theory is that HIV patients have lower levels of intracellular glutathione, a substance which may help protect against toxic byproducts of the drug. There may also be a genetic predisposition to this drug reaction; certainly there seems to be a racial difference, with Black patients, both in the U.S. and other countries, being much less likely to have adverse reactions to TMP-SMX. (1)
Last October, AIDS TREATMENT NEWS described an eight-day desensitization procedure reported by Marcus Conant, M.D., and his associates at the Eighth International Conference on AIDS (in Amsterdam, July 19-24, 1992). They reported successful desensitization in 21 of 25 patients with previous adverse reactions to TMP-SMX. Also, researchers at Kaiser Permanente Medical Center in Los Angeles described an alternative one-day desensitization procedure (reported by D. Gluckstein and J. Ruskin at ICAAC -- the Interscience Conference on Antimicrobial Agents and Chemotherapy -- in Anaheim, California, October 14, 1992, abstract number 1475). They reported success in 15 of 20 patients. Recently we spoke with Brian Lipson, M.D., an allergist/immunologist in Redwood City, California. He had worked with Gluckstein and Ruskin at Kaiser in developing their desensitization method, although he was not one of the authors of the ICAAC report. Recently he improved the procedure, by pretreating his patients with prednisone and antihistamines on the day before and the day of the desensitization. Antihistamines are continued for one month afterwards. Dr. Lipson has treated almost 20 patients with only one failure. That patient had not been pretreated with prednisone and antihistamine.
Dr. Lipson noted that a RAST test to sulfamethoxazole may be helpful, to screen out patients at risk for anaphylactic reaction. During the desensitization, the patient has an IV access as a precaution, in case emergency treatment is needed. The TMP-SMX itself is given orally. The dose is increased every fifteen minutes, with vital signs and peak flow measured before the next dose.
The entire procedure takes 12 hours, and can be done either in a hospital or in an outpatient clinic. After desensitization, patients take one DS TMP-SMX daily. Some physicians give the drug three times a week, but daily use seems less likely than intermittent use to cause a drug reaction. Some patients report redness and warmth for a few hours after each pill, but this usually subsides in a couple weeks.
Dr. Lipson, working with the AIDS Community Research Consortium, has developed a protocol for a formal trial of this desensitization procedure, which he hopes to conduct in the near future.
For more information, physicians and patients can contact Dr. Lipson at 415/365-6300.
References
1. For background on reactions to TMP-SMX and other drugs in persons with HIV, see the review article, Drug Hypersensitivity Reactions and Human Immunodeficiency Virus Disease, by Paul J Bayard, Timothy G. Berger, and Mark A. Jacobson, JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, volume 5, number 12, 1992.
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