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
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
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,