TreatmentUpdate59; Vol 7, No. 5 - May 1995
Sean Hosein

Although guidelines by the US Public Health Service suggest that HIV-infected patients should receive preventative doses of Bactrim(R)/Septra(R) every day, some doctors disagree with this schedule. (Bactrim/Septra (B/S) are the brand names of a combination of 2 antibiotics. The regular dose [also called single strength] has 80 mg trimethoprim and 400 mg sulphamethoxazole. The double strength (DS) has 160 mg trimethoprim and 800 mg sulphamethoxazole.) A few studies suggest that using B/S 3 times per week may be as effective as daily use in preventing PCP. Intermittent doses of B/S may be less toxic for patients and may delay the growth of microbes which are resistant to that drug.

Researchers in California have been conducting experiments on HIV-infected subjects with B/S and AZT. Preliminary results from their work suggest that B/S three times weekly is easier to tolerate than daily doses.

* STUDY DETAILS

Researchers used data from 107 HIV-infected subjects who entered the study with less than 200 CD4+ cells (the average CD4+ cell count was about 140 cells). Subjects who had severe and life-threatening reactions to sulpha drugs were not allowed to enter this study. Subjects randomly received either B/S single strength twice daily or the same dose taken on Monday/ Wednesday/Friday. Some subjects also received 10 mg/day leucovorin, an artificial form of the B-vitamin folic acid, to protect their bone marrow from the side effects of AZT and B/S. Initially subjects received 1 g/day of AZT which was later reduced to 500 mg/day. Researchers did not release details on the sex of subjects.

* RESULTS

Forty-two percent (42%) of 52 subjects receiving daily B/S had to stop taking that drug because of bone marrow toxicity. For subjects taking B/S thrice weekly 24% had to stop for the same reason. Using leucovorin did not seem to have any effect in reducing bone marrow toxicity or influencing which group of subjects left the study. However, researchers noted that subjects who received leucovorin were 6 times less likely to develop bone marrow toxicity than subjects not taking that drug. This difference was not statistically significant. Subjects taking B/S thrice weekly were more likely to keep taking the drug (68%) than subjects taking the daily dose (51%). This difference between the two arms of the study was statistically significant; that is, not likely due to chance alone.

* TOXICITY

The most common side effect was "headache". Problems with intestinal toxicity were reported, with "nausea" being the most common. Fatigue was also another side effect in a small number of subjects. Interestingly, serious bone marrow damage did not occur. A small number of subjects stopped using B/S because they developed several side effects including 'neurological complaints (the doctors did not provide further details), fever and fatigue'. The researchers checked a number of factors (including high doses of AZT versus low; AIDS versus ARC) but these did not help them predict which subjects would develop drug toxicity.

* WHY WAS THERE A DIFFERENCE?

The researchers are not sure why subjects receiving thrice weekly B/S were better able to tolerate the drug than those taking it every day. No subject receiving B/S developed PCP. One subject developed the life-threatening brain infection 'crytpo' (Cryptococcus neoformans) and another a bacterial infection. No subject developed infections such as toxo or MAC which can be affected by B/S. As subjects taking B/S three times weekly were much more likely to continue taking their drug than those who received it daily, this may have an impact on who develops infections such as PCP/toxo over the long term.

REFERENCES:

1. Bozzette SA, Forthal D, Sattler FR, et al. The tolerance for Zidovudine plus thrice weekly or daily trimethoprim-sulfamethoxazole with and without leucovorin for primary prophylaxis in advanced HIV disease. American Journal of Medicine 1995;98:177-182.

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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