Prophylaxis: New One-Day Sulfa Desensitization Procedure

The most effective prophylactic [preventive] treatment for
avoiding pneumocystis in persons with low T-helper counts is oral
trimethoprim-sulfamethoxazole (TMP-SMX, best known by the brand
names Septra, or Bactrim, although less expensive generic
versions are available). TMP-SMX also appears to be highly
effective for preventing toxoplasmosis.

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.