Garlic & Marijuana Interactions with HIV Drugs

Herbs & other complementary or alternative therapies are widely used in HIV-infected patients despite a general lack of knowledge on their adverse effects and drug interactions. Three posters at the Retrovirus Conference addressed garlic & marijuana.

The effect of garlic supplements on the disposition of saquinavir was studied in 10 healthy volunteers by Steve piscatelli at the NIH (abstract 743). Subjects had plasma samples collected for saquinavir levels on saquinavir alone and then after 3 weeks of a twice daily garlic supplement. Saquinavir levels were again studied alone after a 3-week washout period. Overall, there was a decrease in the saquinavir AUC and Cmin of approximately 50%. The mechanism appeared to be a prolonged induction of metabolism since most patients did not return back to their baseline levels after the washout. The AUC, trough, and Cmax returned only to 60-70% of baseline values. This study raises questions. For example, would a decrease be seen when saquinavir is given with ritonavir, as commonly used? What is the actual mechanism, and does dietary garlic affect antiretroviral drug levels? Ongoing studies with other herbs may help to answer some of these issues.

Marijuana is often used in HIV-infected for a variety of reasons but it is currently unknown if its use affects the pharmacokinetics of protease inhibitors. A study by Fran Aweeka (abstract 745) from UCSF examined the effects of marijuana on the pharmacokinetics of indinavir and nelfinavir in HIV-infected patients. Subjects on stable IDV or NFV for 8 at least weeks were randomized to marijuana 4% THC cigarettes, dronabinol 2.5 mg capsules, or placebo, (all given three times daily) and plasma samples were collected at baseline and after 14 days. The groups receiving the cigarettes had nonsignificant decreases in indinavir and nelfinavir Cmin of 34% and 12%, respectively. The only statistically significant change was a modest 14%decrease in the indinavir Cmax. The other two treatment groups did not significantly alter any of the indinavir or nelfinavir pharmacokinetic parameters.

In another study from Don Abrams (abstract 744) at UCSF 67 HIV-infected patients on a stable IDV or NFV regimen were randomized to 3.95% tetrahydrocannabinol marijuana cigarette, dronabinol 2.5 mg or placebo. They looked at changes in CD4s & viral load after 21 days. At baseline 55% had <50 copies/ml and Cd4s were 300. There were no significant differences found in CD4s & viral changes between the 3 arms. Abrams reported there was no statistically significant difference across the 3 arms but there was a 17% reduction in NFV AUC-8 (p<0.04) and a 24% reduction in IDV AUC-8 (p<0.07) in the group receiving the marijuana cigarette. Abrams concluded smoking marijuana has no significant short-term detrimental effects on "standard safety parameters" for patients on stable PI regimens.

Based on these data, it appears unlikely that marijuana cigarettes will markedly affect antiretroviral pharmacokinetic, but longer term clinical trials should be instituted to evaluate clinical significance. Although, there were no changes observed in CD4 count or viral load although changes in these parameters may take longer to be seen.