Background and objectives: The use of cannabinoids for appetite stimulation and the management of wasting and antiretroviral side-effects has become a common practice in the care of HIV-infected individuals. We present pharmacokinetic data from a randomized placebo-controlled study designed to evaluate the metabolic effects of smoked marijuana and dronabinol in HIV-infected patients receiving indinavir (IDV) or nelfinavir (NFV).
\r\nMethods: Subjects on stable regimens containing IDV 800 mg every 8 h (n = 28) or NFV 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95% THC marijuana cigarettes, dronabinol 2.5 mg capsules or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. The changes in NFV and IDV pharmacokinetics were measured as the median percentage change from baseline.
\r\nResults: At day 14, the 8-h area under the curve (AUC8) changed by 10.2% (P 0.15), maximum concentration (Cmax) by 17.4% (P 0.46), and minimum concentration (Cmin) by 12.2% (P 0.28) for patients in the NFV marijuana arm (n 11). Similar decreases had occurred by day 14 among patients in the IDV marijuana arm (n 9): AUC8 had changed by 14.5% (P 0.074), Cmax by 14.1% (P 0.039), and Cmin by 33.7% (P 0.65).
\r\nConclusion: Despite a statistically significant decrease in Cmax of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy.
\r\nInclusion criteria: at least 18 years old, have documented HIV infection, and be on a stable antire- troviral treatment regimen that included either IDV or NFV as the sole PI in addition to nucleoside and/or non-nucleoside reverse transcriptase inhibitors, for at least 8 weeks prior to enrollment. Subjects were also required to have a stable viral load, de®ned as less than a threefold change in HIV RNA level for the 16 weeks prior to enrollment. All subjects were required to have prior experience smoking marijuana (defined as six or more times) to ensure that they knew how to inhale and what neuropsychiatric effects to expect.
\r\nExclusion criteria included the following: any active opportunistic infection or malignancy requiring acute treatment; unintentional loss of ≥10 percent of body weight during the past 6 months; current substance dependence; methadone maintenance; use of tobacco or cannabinoids (smoked or oral) within 30 days of enrollment; history of serious pulmonary disease; pregnancy; and Stage II or higher AIDS dementia complex. Laboratory exclusion criteria were hematocrit < 25% and hepatic transaminase elevations to greater than five times the upper limit of normal.
\r\n