TreatmentUpdate61; Volume 7, No. 7 - July 1995
Sean Hosein

Although Bactrim/Septra is usually the first choice of doctors when prescribing preventative therapy against PCP/toxo, there are some people who cannot tolerate the drug because of allergies to sulpha or its side effects. Doctors may then choose other therapies such as aerosol pentamidine, dapsone-pyrimethamine and Mepron. Other doctors may engage in desensitization, that is, giving their patients small doses of Bactrim/Septra (B/S), then gradually raising the dose. Details on desensitization have appeared in TreatmentUpdate60 and will also appear in future issues. We now report results from a trial in Spain comparing the effectiveness of antibiotic regimens in preventing PCP and toxo.

* STUDY DETAILS

Researchers provided details on 200 subjects (164 men and 36 women), all of whom had less than 200 CD4+ cells. The average CD4+ cell count ranged between 132 and 142 cells. Over 80% of subjects were using AZT when they entered the study. Researchers randomly assigned subjects to one of 2 arms of the study:

+ 1 double-strength tablet of B/S or + dapsone 100 mg and pyrimethamine 50 mg (D-P) twice weekly on "Tuesdays and Fridays."

All drugs were taken by mouth. Subjects experiencing side effects could switch to the other study drug(s) or use aerosol pentamidine. Those subjects experiencing side effects could also use aerosol pentamidine 300 mg/month with or without "pyrimethamine (50 mg [three times]) weekly." At least half of the subjects were monitored for at least 430 days, some for as long as 810 days. No subject in this study had had PCP/ toxo before enrolling.

* RESULTS--PCP

One year into the study, the following proportion of subjects in each group developed PCP:

+ B/S - 0% + D-P - 4%

After 2 years the results were:

+ B/S - O% + D-P - 11%

These differences were statistically significant. The researchers noted that 5 of 6 subjects who developed PCP/toxo had stopped taking their study drugs "at least 2 months before [they developed] PCP and had received no [anti-PCP drugs] during that period."

* RESULTS--TOXO

Equal proportions of subjects (65 who received B/S and 66 who received D-P) tested 'positive' when their blood samples were checked for antibodies against the parasite that causes toxo (T. gondii), indicating that at one time they were infected with that parasite." The following proportion of subjects in each arm developed toxo after 1 year:

+ B/S - 0% + D-P - 2%

After 2 years the results were:

+ B/S - 4% + D-P - 7%

These differences were not statistically significant.

* DEATHS AND OTHER ISSUES

Fifteen subjects in the B/S group and 14 in the dapsone- pyrimethamine group died during the study. The causes of death were not statistically significant between the two groups. Four subjects receiving B/S developed MAC infection compared to 2 subjects in the D-P arm. Subjects in the D-P arm were more likely not to take their drugs than subjects in the other arm of this study. This difference was statistically significant.

* SWITCHING DRUGS

About 10% of subjects moved from one arm of the study to the other in roughly the same proportion. According to the researchers "none of these [subjects] developed EPCP or toxo]."

* SIDE EFFECTS

Subjects receiving B/S were more likely to develop:

+ fever + pain in the intestine or vomiting.

While subjects given D-P were more likely to have:

+ lower-than-normal levels of red blood cells.

* A NOTE ABOUT ddI

A small number of subjects were also using ddI and dapsone. These subjects took their dapsone 2 hours before or after they took their ddI to make sure that absorption of dapsone was not affected by ddI. Subjects taking ddI were not more likely (than other subjects) to develop PCP/toxo.

* CONCLUSION

The doctors concluded that taking B/S 3 days per week was "effective" protection against PCP/toxo in subjects who had never had either of those conditions before. Although D-P was less effective, the doctors considered it a good regimen. The study researchers found that "social problems" (this term was not explained), some of which were related to injection drug use, caused some subjects not to take their drugs as directed. They also think that giving subjects drugs on an intermittent basis made them less likely to switch from one drug to another.

REFERENCES:

1. Podzamczer D, Salazar A, Junenez J. et al. Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for simultaneous primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients infected with HIV. Annals Internal Medicine 1995;122(10):755- 761.

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Copyright © 1995 - 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