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

One fungus that attacks the brain and spinal cord of people with AIDS is C. neoformans and it causes the life-threatening complication commonly called cryptococcal meningitis. Symptoms can include:

+ confusion + lethargy + loss of sense of pain

Doctors may puncture the spinal cord to get a sample of CSF (cerebrospinal fluid in which the brain and spinal cord float), which is then tested to find out if it has any fungus. Analyzing CSF samples for white blood cells, glucose and protein levels can also provide information about this condition.

* TREATMENT

Before the release of fluconazole, standard therapy was intravenous AmB and flucytosine, a regimen likely to cause side effects. Now doctors can prescribe two weeks (or more if necessary) of intravenous amphotericin B (AmB) at a dose of 0.7 mg/kg/day for 2 weeks, followed by oral fluconazole in a dose between 200 and 400 mg/day. Some doctors prolong the exposure to AmB depending on the response to treatment. There are reports of doctors using fluconazole alone as treatment, although it may not be as powerful as AmB. Once recovered, patients will have to take maintenance doses of an antifungal drug to prevent the disease from returning. Some get intermittent doses of AmB, fluconazole or itraconazole.

* STUDY DETAILS

Doctors in Venice enrolled 31 HIV-infected subjects (29 males and 2 females) with "suspected" crypto in their study. Technicians performed tests to confirm that these people did have crypto. Their average CD4+ cell count was 45 (cells). Researchers gave the subjects a small dose of AmB to make sure that they could tolerate it. Subjects who did have the fungus in their blood/CSF eventually received intravenous AmB 1 mg/kg/day for 2 weeks. Subjects could receive the drug beyond the initial 2 weeks of the study if they were not improving quickly. Subjects received iv AmB over a period of 4 to 6 hours, mixed with Intralipid or 5% sugar solution. They also received flucytosine in doses between 100 and 150 mg/kg/day. Once subjects completed the initial 2 weeks successfully, that is to say, they began to recover, they could receive either fluconazole or itraconazole 300 mg/day orally.

* RESULTS RECOVERY/SURVIVAL

The doctors decided that 29 of the 31 subjects responded well to the first 2 weeks of iv therapy. Two subjects did not recover despite receiving iv AmB and iv fluconazole. One of the 2 subjects died from crypto, however researchers were not certain what caused the other subject to develop further problems.

* RESULTS LONG TERM SURVIVAL

On average subjects were monitored for up to 1 year. During this time 3 subjects developed crypto again. One had crypto return 4 months after the initial course of AmB. This subject died despite a course of high dose iv AmB. The other 2 subjects developed crypto 6 months after their first treatment and recovered once they were re-treated with AmB and flucytosine. After 1 year, 19 of the original 31 subjects were dead, although only 2 of the 19 died from complications caused by crypto.

* TOXICITY

While receiving iv AmB, 7 subjects developed kidney damage, detected by high levels of creatinine in their blood. Five subjects had to stop taking the drug until their kidneys recovered and the other 2 had to have their dose reduced. The five subjects who stopped receiving AmB took between 400 and 600 mg/day of fluconazole or itraconazole for "2 additional weeks before [they began maintenance therapy]." Twenty-seven subjects received flucytosine for an average of 11 days and were able to tolerate the drug. Four subjects did not receive flucytosine because 3 had low levels of white blood cells and the 4th was taking drugs (sulfadiazine and pyrimethamine, that could damage the bone marrow; the researchers wanted to minimize any potential damage to the bone marrow caused by flucytosine.

The researchers suggested AmB damage to the kidney usually happens when patients receive the drug over long periods of time. Their approach, high dose AmB for 2 weeks caused kidney problems in only 23% of subjects. As we report below, other research teams are experimenting with higher doses of fluconazole with or without flucytosine.

REFERENCES:

1. de Lalla F. Pellizzer G. Vaglia A, et al. Amphotericin B as primary therapy in patients with AIDS: reliability of relatively high doses administered over a relatively short period. Clinical Infectious Diseases 1995;20:263-266.

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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