GMHC Treatment Issues; September 1, 1996
Derek Link

At 8 in the morning on August 4, California drug agents burst open the doors of the Cannabis Buyers' Club, which distributes marijuana for medicinal use to people in the San Francisco area with AIDS, cancer and other conditions. Besides making off with the club's supply of pure marijuana and drug-laced baked goods and $60,000 in cash, the agents seized confidential medical records for the organization's 12,000 members.

The buyers' club has been openly selling marijuana primarily to people with AIDS- or cancer-related weight loss since 1991. The organization's raison d'Étre enjoys popular support in the region, and elected city officials have protected the club from police harassment. State Attorney General Dan Lungren ordered the assault on the compassionate-use organization without consulting local officials.

The California Attorney General's office says it was gathering evidence that healthy individuals were obtaining marijuana for recreational use through the club. But many see the raid as an obvious attempt to derail Proposition 215. This ballot measure, which goes before voters in November, would grant people in California the right to grow or purchase marijuana for personal medicinal use. The Attorney General opposes Proposition 215. Many of the organizers of the campaign, who were involved in the buyers' club, now must make time to contend with criminal investigations rather than work on the ballot effort, which the raid helps to discredit. Anyone who wishes to help or make financial contributions to the organization should contact Californians for Compassionate Use at 415/621-3986.

**CMV Retinitis Study Aborted

A study of the experimental anti-CMV drug MSL 109, made by Protein Design Labs, has been halted after an interim analysis found that the treatment offered no benefit over placebo. MSL 109, also called Protovir, is a monoclonal antibody targeted at CMV (see Treatment Issues, July/August 1995, pages 4, 7-8). The failure of the compound comes as a surprise, since in an earlier uncontrolled study, it seemed to prolong time to progression of CMV retinitis when added to standard of care medications. That trial (reported in Antiviral Research, 1992; 16 (suppl 1):111), found progression was delayed by more than 200 days on average in seventeen volunteers, about twice the delay treatment with ganciclovir or foscarnet alone usually achieves.

On the basis of these early promising results, large randomized studies were initiated. The discontinued trial sponsored by the National Eye Institute's Studies of the Ocular Complications of AIDS (SOCA) and the AIDS Clinical Trial Group (ACTG), had enrolled over 200 of the planned 320 patients with newly-diagnosed or recurrent CMV retinitis. All patients were treated with currently approved anti-CMV therapy, but half were randomized to receive MSL 109 (60 mg every two weeks) in addition to the other medications.

The investigators chose to perform the interim analysis after a Data and Safety Monitoring Board noted that more deaths had occurred among the patients who were receiving MSL 109. The difference in mortality only occurred in those patients with recurrent retinitis. According to Dr. Curtis Meinhart of SOCA, this may have been a fluke, since the incidence of death was lower than usual in those randomized to receive placebo. Be that as it may, the interim analysis found that the addition of MSL 109 did not delay time to progression (65 days in the MSL 109 arm versus 66 days in the placebo).

Two other large MSL 109 studies are still ongoing. One is a CMV prophylaxis study in bone marrow transplant patients. The Data and Safety Monitoring Board recommended introducing no changes to this study, after finding no increase in mortality or side effects in participants taking MSL 109.

A second study conducted by the ACTG, study #266, has been temporarily placed on hold. A number of this study's investigators were involved in the earlier small study that reported positive results from MSL 109. Since the doses in ACTG 266 are the same or lower than the ineffective doses used in the SOCA trial, the ACTG study team has recommended enrolling new patients at higher doses of MSL 109. Those already enrolled on the study would have the option of quitting the study or switching to the higher doses. This plan, though, is dependent upon approval by the specific medical centers supervising the trial, the ACTG, the National Institute of Allergies and Infectious Diseases and the FDA.

**Anabolic Steroid Boosts Weight

A study of nandrolone decanoate (Deca-Durabolin) has found that the anabolic steroid can increase weight in people with HIV, according to a report at the Eleventh International Conference of AIDS in Vancouver (Mo.B.423). The study, conducted in Chicago and New Orleans, randomized 73 people (one woman and 72 men) with low testosterone, fatigue, depression or wasting to intramuscular nandrolone (100 mg per week) or placebo. After twelve weeks, those on placebo received nandrolone for another twelve weeks. All trial volunteers were encouraged to exercise.

After the first twelve-week period, those on treatment had gained a statistically significant total of 1 kilogram compared to an increase of 0.1 kg on placebo. The group receiving nandrolone experienced a greater increase both in fat-free mass (2.3 kg versus 0.5 kg in those on placebo) and body cell mass, another measure of lean body mass (2.3 kg versus 1.0 kg in those on placebo), although the latter measure did not reach statistical significance. A large amount of the gained weight may have been water. Still, according to one of the investigators, Daniel Berger, M.D., "patients felt much better on drug."

Dr. Berger noted that "patients in other parts of the country are doing higher doses, but mostly we wanted to know whether it was safe for our patients." The steroid had no observed negative effect on viral load or immune status and increased levels of hematocrit (a measure of red blood cell level) and hemoglobin, which are low in many people with HIV, especially those on AZT. Levels of free and total testosterone decreased in the treated patients. A few patients withdrew from the study due to mood swings, restlessness or increased libido. Insomnia, impotence and acne were reported by some patients.

There have been fears, based on anecdotal observations, that anabolic steroids promote Kaposi's sarcoma. One volunteer treated with nandrolone developed KS. No changes in KS during the study were seen in three persons on treatment who had KS at baseline -- but one developed pulmonary KS one month after the study concluded. Although, the occurrence or worsening of KS may have little to do with use of the steroid, the study presenter at the International Conference, Dr. Gary Bucher of the Centers for Special Immunology site in Chicago, concluded that "Deca-Durabolin should be used with caution in patients with KS until larger studies are done."

The experience of the one woman in the study illustrates a potential danger of anabolic steroid use in women with HIV. She gained a few pounds, but stopped menstruating. After going off treatment, her weight remained stable, but her periods have not yet restarted.

The same investigators from the Centers for Special Immunology are planning a study comparing nandrolone to growth hormone in patients with wasting. The trial is slated to begin in the next three or four months. Treatment with human growth hormone, which was just approved by the FDA for use in AIDS wasting syndrome, costs about 100 times treatment with 100 mg per week of nandrolone.

**Studies Strengthen Link between HHV-8 Virus and KS

Two recently published studies strengthen the evidence that infection with HHV-8, also known as KSHV or the KS Herpes Virus, leads to the development of Kaposi's sarcoma lesions. Both studies used new blood tests that detect antibodies to the virus.

In one of the studies, blood from 913 people was tested for HHV-8 antibodies by researchers from the University of California San Francisco (Nature Medicine, August 1996;2:862-863, 918-928). The team found strong evidence suggesting that the virus is sexually transmitted. The highest incidence of HHV-8 infection (35%) was seen among gay or bisexual men who became HIV-infected through sex. A high rate of HHV-8 infection was seen among HIV-negative people with syphilis, 8% of whom had antibodies to the virus. Only 3% of HIV-positive people with hemophilia (who acquired HIV through blood products) and only 1% of blood donors without sexually acquired diseases had evidence of HHV-8 infection. Finally, underscoring the link between the herpes virus and the malignancy, the researchers found that 83% of tested patients with KS had antibodies to HHV-8.

Very similar results were published in the New England Journal of Medicine (July 25, 1996; 335:233-41) by Shou-Jiang Gao, Ph.D. et al (in collaboration with Yuan Chang and Patrick Moore -- the Columbia University team that first identified HHV-8). These scientists found antibodies to HHV-8 in 80% of 40 HIV-positive gay men with KS. Only 18% of 40 HIV-positive gay men without KS tested positive for antibodies to the virus, and none of 122 HIV-negative blood donors, 22 patients infected with Epstein Barr Virus, or 20 men with HIV and hemophilia had HHV-8 antibodies.

Perhaps the most important finding of the study was that 21 of the 40 HIV-positive men with KS developed antibodies to HHV-8 six to 75 months prior to the appearance of KS lesions. The researchers believe that the development of antibodies to HHV-8 is not the result of reactivation of a latent virus in immune-compromised patients. They base this view on the very low rate of antibodies in comparable gay men with HIV but no KS. The data suggests that HHV-8 infection is newly acquired, probably through sexual relations.

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