A study by researchers from the University of California, San Francisco has found that patients with HIV infection taking protease inhibitors do not experience short-term adverse virologic effects from using cannabinoids. According to Donald Abrams, MD, lead author of the study and professor of clinical medicine in the UCSF Positive Health Program at San Francisco General Hospital Medical Center, this was the first attempt to study the effects of marijuana in people with HIV and one of the most comprehensive studies about the effects of marijuana on the immune system.
Research findings were reported today (July 13) at the XIII International AIDS Conference in Durban, South Africa.
The study focused on HIV patients whose antiretroviral regimens included protease inhibitors because cannabinoids are metabolized by the same systems in the liver as protease inhibitors. The inpatient study lasted 21 days and measured changes in HIV RNA levels between baseline and day 21. RNA is a major component of retroviruses such as HIV.
The key measure of immunological effects was the Bayer Quantiplex HIV-1 bDNA version 3.0 assay test. This test measured the amount of HIV present in the blood, down to 50 copies per milliliter of blood (copies/ml). Virus that is present in quantities less than 50 copies/ml is an undetectable level of virus and is considered the primary indicator of success in suppressing the virus. Rises in HIV RNA levels are a sign that the HIV virus is actively replicating and are associated with adverse immunological events.
The study was undertaken by the Community Consortium, the San Francisco community based HIV clinical trials group, because of the widespread use of smoked marijuana by HIV patients in San Francisco. Sixty-seven subjects were enrolled. Ninety-six percent were male and 67 percent were over 40 years old. Thirty of the subjects were on antiretroviral regimens containing the protease inhibitor indinavir, and 37 were on regimens containing the protease inhibitor nelfinavir.
HIV RNA levels were measured twice at baseline and then at days 2, 5, 8, 11, 14, 17, 19, and 21. Thirty-seven (55 percent) of the subjects entered the study with HIV RNA levels of less than 50 copies/ml. Ten (16 percent) had HIV RNA levels between 50 and 499 copies/ml. Thirteen (19 percent) had HIV RNA levels between 500 and 9999 copies/ml and 7 (10 percent) had levels over 10,000 copies/ml.
Subjects were randomized to one of three groups receiving--three times a day before meals--either a marijuana cigarette containing 3.95 percent THC, the active ingredient in marijuana; an oral tablet containing THC (2.5 mg. oral dronabinol); or an oral placebo. Twenty-one were randomized for smoked marijuana, 25 for oral dronabinol, and 21 for the oral placebo.
Sixty-two subjects completed the study. One subject in the smoked marijuana arm left the study because of neuropsychiatric symptoms; another in the same arm also experienced neuropsychiatric symptoms but was treated and remained in the study. One subject in the oral dronabinol arm left the study due to neuropsychiatric effects, and one left due to headache and nausea possibly related to the study drug.
Other adverse effects that did not cause the subjects to leave the study were an occurrence of tachycardia (rapid heartbeat) in the smoked marijuana arm and a kidney stone (possibly related to the protease inhibitor, indinavir) experienced by a subject in the oral dronabinol arm. No adverse events were reported in the placebo arm.
Of the 62 subjects who completed the study, the 36 with undetectable HIV RNA levels remained at these levels. All 26 subjects with detectable HIV RNA levels experienced declines in HIV RNA levels. Of those, the subjects who smoked marijuana or took oral dronabinol experienced slightly greater decreases in HIV RNA levels than did subjects who took the placebos.
According to Abrams, "The slightly better decline experienced by those using marijuana or dronabinol is intriguing, but not statistically significant. The good news is that there is no statistical difference between the three groups." At this time, he attributes the decline in HIV RNA levels to better adherence by the subjects to their drug regimens. "Antiretroviral therapy was directly observed. Subjects did not miss a dose," said Abrams. "Studies of the impact of marijuana and dronabinol on protease inhibitor levels and immune system function are still ongoing," he added.
One difference noted by Abrams between the three arms was in caloric intake and weight gain. "All three groups gained weight. Part of that was due to regularly scheduled meals and snacks being readily available. However, the placebo arm averaged a gain of 1.30 kilograms while the subjects who took oral dronabinol gained an average of 3.18 kilograms. Those who smoked marijuana gained an average of 3.51 kilograms. Caloric intake reflected the same order."
The co-authors include Roslyn J. Leiser, Starley B. Shade, Joan Hilton, and Tarek Elbeik, all of UCSF. This research was supported by a research grant, R01 DA1 1607, from the National Institute on Drug Abuse, a part of the National Institutes of Health, which also supplied the marijuana cigarettes for the trial. The dronabinol and placebo were supplied by Roxane, Inc., Columbus, Ohio.