Short-term effects of cannabinoids in patients with HIV-1 infection - A randomized, placebo-controlled clinical trial

Background: Cannabinoid use could potentially alter HIV RNA levels by two mechanisms: immune modulation or cannabinoid-protease inhibitor interactions (because both share cytochrome P-450 metabolic pathways). Objective: To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients. Design: Randomized, placebo-controlled, 21-day intervention trial. Setting: The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California. Participants: 67 patients with HIV-1 infection. Intervention: Participants were randomly assigned to a 3.95%-tetrahydrocannabinol marijuana cigarette, a 2.5-mg dronabinol (delta-9-tetrahydrocannabinol) capsule, or a placebo capsule three times daily before meals. Measurements: HIV RNA levels, CD4(+) and CD8(+) cell subsets, and pharmacokinetic analyses of the protease inhibitors. Results: 62 study participants were eligible for the primary end point (marijuana group, 20 patients; dronabinol group, 22 patients; and placebo group, 20 patients). Baseline HIV RNA level was less than 50 copies/mL for 36 participants (58%), and the median CD4(+) cell count was 340x10(9) cells/L. When adjusted for baseline variables, the estimated average effect versus placebo on change in log(10) viral load from baseline to day 21 was -0.07 (95% CI, -0.30 to 0.13) for marijuana and -0.04 (CI, -0.20 to 0.14) for dronabinol. The adjusted average changes in viral load in marijuana and dronabinol relative to placebo were -15% (CI, -50% to 34%) and -8% (CI, -37% to 37%), respectively. Neither CD4(+) nor CD8(+) cell counts appeared to be adversely affected by the cannabinoids. Conclusions: Smoked and oral cannabinoids did not seem to be unsafe in people with HIV infection with respect to HIV RNA levels, CD4(+) and CD8(+) cell counts, or protease inhibitor levels over a 21-day treatment.