AIDS TREATMENT NEWS No. 109 - August 17, 1990
Denny Smith

Azithromycin, an antimicrobial drug which has been discussed for over two years as a potential treatment for toxoplasmosis, is now in a pilot study at Pacific Presbyterian Medical Center in San Francisco to treat MAI. Since this is a pilot study looking essentially for drug safety, only fifteen persons will be followed. Participants will receive 500 mg of an oral formulation daily. When safety is established, trials will begin at other sites around the U.S.

We spoke to the principal investigator of the study, Lowell Young, M.D., who is Chief of Infectious Disease at Pacific Presbyterian Medical Center and Director of the Center's Kuzell Institute, which will oversee the azithromycin trial. Dr. Lowell shared several thoughts with us about the future of research for MAI therapies.

Azithromycin has appeared promising for some time in laboratory studies for activity against MAI, Toxoplasma, and Pneumocystis. There may soon be a decision to begin human trials of the drug for toxoplasmosis. Another new compound, called clarithromycin, which was disappointing when applied to Toxoplasma, was shown to be as promising as azithromycin against MAI in French and German pilot studies. Dr. Young said that the main distinction so far is that azithromycin remains in the body longer than clarithromycin. He is eager for trials of both drugs to progress, but acknowledges the unlikelihood that either of them alone will be effective against MAI, since the history of mycobacterial therapies points to a reliance on combinations of treatments. Both of these drugs are available in some countries outside the U.S.

The Food and Drug Administration recently granted orphan drug status to TLC G-65, or Gentamicin Liposome Injection, manufactured by the Liposome Company. Gentamicin sulfate is already approved to treat certain bacterial infections, but like many antibiotics, it does not adequately reach the interior of human cells, where MAI resides. Liposomes naturally penetrate cell walls and so are sometimes used to encapsulate and deliver a given drug to intracellular targets. The use of liposomal preparations represents a welcome expansion of options to treat MAI and possibly other opportunistic infections as well. TLC-65 is nearing clinical trials, and interested physicians can call the manufacturer at 609/452-7060, and speak to Mr. Ed Silverman.

The Houston Clinical Research Network and St. Francis Hospital in San Francisco are among 16 trial sites nationwide now recruiting for studies of rifabutin (Ansamycin), an experimental drug, as a prophylactic measure for controlling latent MAI infections. (Clofazimine, an approved medication, is another agent under study for this purpose, given 50 mg daily.) The rifabutin trials are placebo-controlled. Interested persons in the Houston area can call 713/528-5554, and in San Francisco 415/775-4321, ext. 2512. Other rifabutin trial sites are located in Arizona, the District of Columbia, California, Florida, Georgia, Maryland, Missouri, New Jersey, New York, Ohio, Pennsylvania, Texas, Virginia, and Wisconsin. Information on local trials can be obtained by calling the manufacturer, Adria Laboratories, at 614/764-8382.

The Treatment + Data Committee of ACT UP/New York has designed a survey for collecting data or opinions from physicians who have had experience treating MAI. Their successes or failures with various drugs could provide valuable information when the results are compiled and studied for trends. To obtain a copy of the survey, interested persons can call Garance France-Ruta at 212/532-0363, or mail a request to Garance, c/o the PWA Health Group, 31 W. 26th St., Fourth Floor, New York, NY, 10010. The analyzed results will be available to participating physicians.

AIDS TREATMENT NEWS has received anecdotal reports from or about several people who experienced serious hearing loss due to inner ear nerve damage during treatment with amikacin, one of the drugs frequently used in MAI treatment regimens. "Ototoxicity," including balance difficulties as well as hearing loss, is already known to be a possible side effect of drugs called aminoglycosides, which include amikacin as well as gentamicin, mentioned above. We urge people diagnosed with MAI and their physicians to be cautious and aware of this potentially irreversible problem. (Dr. Young told us that the toxicity of amikacin should be well-known and that it is not usually a worry when using the drug for less than a month; he noted that the danger is heightened in older people. The question of whether the liposomal gentamicin will carry the same risks as the standard formulation has not yet been answered).

Note: AIDS-related hearing loss is not always caused by drugs. We have received two other reports of hearing loss, one caused by lymphoma and the other by candidiasis.

The abstracts published at the recent International Conference included a study from Chicago which reviewed the response to treatment in 20 patients diagnosed with disseminated MAI infections. The treatment used was a common combination of four oral drugs, administered indefinitely -- clofazimine, rifampin, ethambutol, and ciprofloxacin -- with an initial limited course of intravenous amikacin. The authors discerned a "favorable clinical/microbiological response" to this therapy in 19 of the 20 patients. Bacteremia in four was either controlled with the addition of amikacin or persisted in its absence. But three patients experienced severe ototoxicity after 60 days of amikacin (abstract Th.B. 517).

Another of the abstracts presented at the Conference discussed the incidence of MAI from a review of the medical records of eleven pediatric patients at Children's Hospital of New Jersey. The authors concluded that diagnosis of atypical mycobacterial infections in children may be delayed for as much as a year and a half, and that symptoms to watch for are abdominal distress, persistent fever or failure to thrive (abstract #2060, Hoyt L and others).

The above items of information may be undramatic by themselves, but represent a net optimism for controlling MAI. Only a year ago, many doctors declined to treat this infection at all, on the assumption that no single drug was convincingly effective against it. Now AIDS-knowledgeable physicians are experimenting with various combinations of agents, and we expect that the ACT UP survey will be of real assistance to them.

566C80 is a new treatment possibility for toxoplasmic encephalitis, which is entering a pilot study for people who have already tried the standard therapy, pyrimethamine with sulfadiazine, but failed to respond or could not tolerate the side effects. Interested persons should contact Barbara Baird, R.N., at the National Institute of Allergy and Infectious Disease, 301/402-0980.

The progress of 566C80, azithromycin, and liposomal drugs into clinical trials is welcome and long-awaited. If these agents continue to look useful, we hope the journey from pilot studies to expanded access is timed to save lives in the very near future.

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