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

Although there are several drugs that doctors can use to treat and prevent the life-threatening lung infection PCP, the brain infection toxo (toxoplasmosis), tuberculosis (TB), and MAC, all these drugs have side effects. In some patients these side effects are mild and in others they are not. Doctors are experimenting with a variety of drugs to see which is right for their patients. In the late 1980s doctors in Germany reported that treatment with between 2 and 3 grams/day of the antibiotic erythromycin was effective against PCP. Researchers in the EU have been experimenting with drugs 'related' to erythromycin such as azithromycin and clarithromycin. We now report on another related drug, roxithromycin.

* STUDY DETAILS

Researchers enrolled 52 HIV-infected adults (46 men, 6 women) who had less than 200 CD4+ cells (the average was about 133 cells). At the time subjects entered the study none had any life-threatening infections. Researchers randomly assigned subjects to one of 3 groups or 'arms'. Eighteen subjects received 300 mg/month of aerosol pentamidine (AP), 17 others received a combination of aerosol pentamidine and roxithromycin (300 mg 3 times daily once per week); and another 17 subjects received roxithromycin in the same dose and schedule as in the other group.

* RESULTS

Subjects given roxithromycin developed life-threatening infections much later than subjects given AP. As well, subjects given roxithromycin were also less likely to develop the life-threatening brain infection toxoplasmosis. These 2 differences were statistically significant; that is, not likely due to chance alone. Subjects receiving roxithromycin were less likely to develop TB and MAC infections. Fungal infections in the throat occurred evenly among the groups of subjects. For the purposes of this report we will include the subjects receiving the combination of AP and roxithromycin with the others who received roxithromycin alone as there were no statistically significant differences between the 2 groups. For the listing of deaths in this study we report the number for each of the three arms.

* INFECTIONS AND DEATH: WHO GOT PCP, TOXO, TB/MAC, AND WHO DIED?

-PCP: 3 subjects on AP

1 subject on roxithromycin

-toxo: 5 subjects on AP 1 subject receiving roxithromycin

-TB/MAC: 4 subjects on AP No subjects on roxithromycin

-Deaths: 4 subjects on AP 3 subjects on AP and roxithromycin 3 subjects on roxithromycin

* TOXICITY

Doctors found that AP was 'well tolerated' by subjects. Researchers had to stop giving roxithromycin to 5 subjects who had "nausea, abdominal pain and skin allergies" and to 1 other subject who had high blood levels of liver enzymes suggesting some liver damage. Upon investigation the researchers found that this last subject had hepatitis C which may have caused the high levels of liver enzymes. They noted that this subject suffered no symptoms of liver (or any other) toxicity. Six weeks after he stopped taking roxithromycin his liver enzyme levels fell to normal. As soon as subjects developed life-threatening infection(s), researchers stopped giving them roxithromycin. Causes of death in this study included various bacterial infections, unintentional weight loss and one case of toxo. No subject died from PCP, TB or MAC infection.

* ROXITHROMYCIN

As many people in Western Europe have greater exposure to the parasite that causes toxo, it is interesting that more subjects receiving roxithromycin did not develop symptoms of toxoplasmosis. The researchers suggest that another study with more patients should be conducted to confirm their findings. Based on their data the researchers suggest that roxithromycin 900 mg/day once a week protects subjects for at least 8 months from developing toxo. The researchers note that the proportion of subjects who stopped taking roxithromycin because of toxicity is similar to withdrawal rates seen in other trials using Bactrim/Septra as PCP prevention. Roxithromycin in this study was supplied by Roussel-Uclaf.

REFERENCES:

1. Durant J, Hazime F, Carles JM, et al. Prevention of Pneumocystis carinii pneumonia and of cerebral toxoplasmosis by roxithromycin in HIV-infected patients. Infection 1995;23 (supplement 1 ):s533- sS38.

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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