AIDS Treatment News #161, October 16, 1992
John S. James

The major disadvantage of co-trimoxazole prophylaxis is that half or more of persons with HIV (compared to only about three percent of the general population) cannot tolerate the drug, due to skin rashes, fever, and other drug reactions, which in rare cases can be life-threatening. No one knows why persons with HIV are more likely to react to this and other drugs. But the consequence of the drug reactions is that many people have had to switch to less effective forms of pneumocystis prophylaxis such as aerosol pentamidine.

Desensitization procedures, in which persons are started on tiny doses of a drug and then the doses are gradually increased, have long been used to overcome sensitivity to certain important drugs such as penicillin. And since 1986, there have been several reports in the literature of desensitizing persons with HIV to co-trimoxazole. But until recently only a few patients had been treated, and the desensitization procedure usually was done in a hospital, so the method did not come into widespread use.

At the Eighth International Conference on AIDS (in Amsterdam, July 19-24 1992), Marcus Conant, M. D., a leading AIDS specialist in San Francisco, presented a poster on outpatient desensitization procedures [Conant M. and Dybul M., Trimethoprim/Sulfamethoxazole Hypersensitivity and Desensitization in HIV Disease, abstract # 3291]. Since then Dr. Conant and his associates have revised the procedure (the published abstract had to be submitted in early March), and prepared detailed instructions for physicians, patients, and pharmacists, so that co-trimoxazole desensitization can be used more widely. Instead of reproducing the instructions here, we will outline what the procedure involves, and provide a phone number so that physicians can get copies of the information packet.

The current procedure was tested in 25 persons with HIV; their average T-helper count was 87. All had had co-trimoxazole reactions, but those who had had very serious reactions (such as Stevens-Johnson syndrome) were excluded.

The desensitization procedure lasted 8 days. On the first day, patients used a one-to-one-million dilution, prepared by a pharmacist, of a commercially available liquid form of co- trimoxazole. Four escalating doses were taken at six-hour intervals from an oral syringe in which the drug was supplied; at the end of the day, the syringe and any remaining drug in it were discarded. Each day the concentration of the solution was increased ten fold. The patient followed an identical procedure of each of the first seven days (making sure to use the right syringe for each day); on day eight, the procedure was different, ending with a double-strength co-trimoxazole tablet, which patients then continued to take every day.

This procedure was successful in 21 of the 25 patients. They have now remained desensitized for an average of over three months. But side effects during the desensitization could be severe; 12 of the 25 patients required treatment with prednisone to suppress the reaction to the drug. Another physician in Dallas used the same procedure and desensitized 24 of 25 patients; however, the one failure developed Stevens-Johnson syndrome, and later died due to complications.

Many other safety precautions were taken. Each patient took the first dose in the physician's office and remained there for an hour. Each needed a friend or other person as home monitor, to watch them after each dose and get help in case of anaphylaxis (a rapid and extreme allergic reaction). Patients were told to drink 3 liters of water per day, use a #15 sunscreen if exposed to the sun, and not interrupt the therapy even for a day or two (unless treatment must be discontinued), because allergic reactions can occur when treatment is restarted. Frequent physician calls to patients and office visits were important to a successful outcome.

This list of precautions is not complete. Obviously the desensitization procedure involves significant risks and must be done under a physician's supervision.

For More Information

Dr. Conant's office has prepared an information packet which includes an explanation and protocol for physicians, written instructions for patients, and instructions for pharmacists on how to prepare the drug dilutions. To obtain a copy, health-care providers should call Christopher King, 415/661-2614.

[Note: On October 14 researchers at Kaiser Permanente Medical Center in Los Angeles described the successful use of a different co-trimoxazole desensitization procedure, which is completed in a single day in a physician's office. AIDS TREATMENT NEWS plans to publish a report on this method in a future issue.]

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