TreatmentUpdate83 - Vol. 9, No. 9 - pp. 3-4; November 1997
Sean Hosein

One of the hallmarks of AIDS is the life-threatening brain infection 'crypto' (cryptococcal meningitis). Signs and symptoms include headache, fever, nausea/vomiting and an "altered mental state." Standard treatment is 4-6 weeks of intravenous amphotericin B (AmB) followed by life-long maintenance therapy with fluconazole or itraconazole. AmB can cause kidney toxicity. In order to reduce this, some doctors decrease the dose and length of time PHAs receive AmB. Another way to avoid the toxicity is to use the liposomal form of AmB called AmBisome. Here the drug is packed into tiny balls of fat called liposomes. These liposomes are supposed to carry the drug exactly where it is needed, that is to tissues infected with the fungus.

In this study of 28 subjects, doctors gave 15 AmBisome and 13 AmB. They found that those who received AmBisome had a more rapid recovery (as measured by lab tests) and experienced less toxicity than others who received AmB. When doctors looked at the change in signs/symptoms while PHAs were treated, the response to the drugs was the same in either group. There were no deaths during the first 3 weeks of the study.

Over a 6 month observation period, no relapses occurred. Although AmBisome is equally effective as AmB, it is more expensive, a factor which may limit its use.

Study Details

Researchers supplied few details about the subjects (gender unknown). The average CD4+ count was 35 cells and none had used protease inhibitors before. Subjects had at least one of the following symptoms:

* headache

* fever

* nausea/vomiting

* "altered mental state".

All subjects had the fungus that causes crypto (C. neoformans) in samples of their CSF--the cerebrospinal fluid in which the brain and spinal cord float. Technicians also detected the fungus in blood samples from some subjects. Doctors randomly assigned half the subjects to receive either 3 weeks of intravenous AmBisome 4 mg/kg/day or AmB 0.7 mg/kg/day. At the fourth week subjects received fluconazole 400 mg/day, later reduced to 200 mg/day.

Results

No subject died during the first 9 weeks of the study. The symptoms of 12 of 15 subjects on AmBisome and 11 of 13 on AmB cleared within the first 3 weeks. When technicians tested CSF samples they found that the fungus cleared much more quickly in subjects receiving AmBisome than AmB. Indeed, within a week, 50% of the group on AmBisome no longer had detectable fungus while only one person on regular amphotericin B had his/her fungus clear.

Results--long-term

At the 10th week, the response to therapy remained the same in both groups. According to the study doctors, no "proven relapses occurred." One subject treated with AmBisome died, after having been admitted to hospital with a reduced level of consciousness.

Doctors are not certain why he died. Two other subjects, one from each group, later died from causes unrelated to crypto.

Results--toxicity

Fewer side effects were reported by subjects on AmBisome compared to those on AmB but this was not statistically significant. Two subjects receiving AmBisome developed a reaction during their first infusion of the drug with symptoms that included a rapid heart beat, fever, shortness of breath, low blood pressure and a tickling cough. Nurses stopped infusing the drug and later resumed the infusion at a lower rate. The reactions did not recur.

Overall

AmBisome appears to cause a more rapid disappearance of the fungus from the CSF compared to AmB as well being less toxic. AmBisome might become more popular if it weren't for its greater expense compared to regular amphotericin B.

REFERENCES:

1. Leenders ACAP, Reiss P, Portegies P, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS 1997;11:1463-1471.

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