Lipodystrophy: Options widen for treatments

Anecdotal evidence supports naltrexone use

The bad news is that lipodystrophy and meta bolic anomalies are on the rise among HIV patients. But the good news is that clinicians now have more choices for treating these problems.

Treatments include the human growth hormone Serostim; an over-the-counter nutritional supplement that research shows reverses the trend of AIDS wasting by promoting lean muscle mass growth; and combinations of drugs and exercise.

For example, a study published earlier this year in the Journal of the American Medical Association showed that an anabolic agent called oxandrolone, combined with a controlled program of progressive resistance exercise, resulted in increased lean body mass and strength in men suffering from AIDS wasting.

Earlier this year, a study showed that a mixture of b-hydroxy b-methylbutyrate, arginine, and glutamine, sold in an orange-flavored dietary supplement called Juven by MTI Biotech in Ames, IA, helped AIDS patients gain muscle weight and reduce body fat. (See article on Juven in April 1999 issue of AIDS Alert.)

But among the most surprising treatments promoted as a possible solution to lipodystrophy is the use of a narcotic.

New York family physician Bernard Bihari, MD, has gathered evidence from his own observational study of HIV patients showing that a small dose of the drug naltrexone can prevent and reverse lipodystrophy.

Bihari, who has had a large AIDS practice for 15 years, began to use naltrexone in 1986 as a way to help patients enhance their immune systems. It surprised Bihari to discover more recently that the drug has an additional benefit of protecting patients against the peripheral fat wasting, metabolic abnormalities, and other fat redistribution problems associated with the use of protease inhibitors and highly active antiretroviral therapy.

Bihari prescribed a 3 mg dose of naltrexone to each of his 136 HIV-infected patients Only four of the patients treated with protease inhibitors and other antivirals developed lipodystrophy. The patients, who had been treated for a mean of 24 months, also maintained undetectable viral loads in 90% of the cases.

Of the four patients who developed lipodystrophy, one patient had stopped taking naltrexone after moving away from New York. About eight months after stopping naltrexone, the patient saw signs of fat redistribution on his body. The same patient’s serum cholesterol level rose to the high 400s, and his triglycerides and fasting blood glucose levels also increased. When the patient got in touch with Bihari and described his condition, Bihari recommended he start again the 3 mg dose of naltrexone once again. The patient began taking it again and has since seen improvements in his cholesterol, triglycerides, and blood sugar levels. Also, his abdominal girth decreased by one-third.

Patients returning to drug improve

Two more of the four patients had similar experiences after they moved to Europe and quit taking naltrexone. They also called Bihari, and on his advice resumed taking the drug. Their lipo dystrophy problems also have improved.

The fourth case also involved a patient who had stopped taking naltrexone because he thought the drug no longer was necessary because the antire tro virals had successfully suppressed his viral load.

"This is just an observational study in private practice, but because the results were so striking, it has more power and significance than observational studies," Bihari says.

DuPont Merck Pharmaceutical Co. of Wilmington, DE, manufactures naltrexone, which received Food and Drug Administration (FDA) approval in the early 1980s in a 50 mg dose, used as an adjunct to block addicts’ heroin high for 20 to 24 hours. At that dosage, the drug has a variety of unpleasant side effects, including anxiety, insomnia, stress intolerance, and enhancement of the heroin craving. A decade later, researchers concluded the drug has a significant benefit in reducing drinking among alcoholics.1 A DuPont study found the drug was safe, with the most common adverse effects being nausea and headache.2 The FDA approved it for that use, as well.

Other studies have recorded less success in using naltrexone for treating autistic children, controlling food intake, and treating other addictions.

Bihari uses a 3 mg dose of naltrexone that most pharmacies can formulate on the premises by putting the naltrexone powder into a capsule. Patients take the 3 mg capsule each night at bedtime. The medication, which Bihari says is covered by insurers for half of his HIV patients, costs about $25 a month.

So far, no clinical trials have been scheduled to study naltrexone’s use by HIV patients. But Bihari is trying to find a drug company that would invest in the research, and he has submitted a paper based on his own observational research to the 7th Conference on Retroviruses and Opportunistic Infections, to be held in early 2000.

References

1. O’Brien CP, Volpicelli LA, Volpicelli JR. Naltrexone in the treatment of alcoholism: A clinical review. Alcohol 1996; 13:35-39.

2. Croop RS, Faulkner EB, Labriola DF. The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. Arch Gen Psychiatry 1997; 54:1,130-1,135.