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.


METHODS
Randomized, placebo-controlled, 21-day intervention trial.


METHODS
The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California.


METHODS
67 patients with HIV-1 infection.


METHODS
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.


METHODS
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 340 x 109 cells/L. When adjusted for baseline variables, the estimated average effect versus placebo on change in log10 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.
Abrams
Donald I
DI
University of California, San Francisco, and Gladstone Institute of Virology and Immunology, San Francisco, California 94110, USA.
Hilton
Joan F
JF
Leiser
Roslyn J
RJ
Shade
Starley B
SB
Elbeik
Tarek A
TA
Aweeka
Francesca T
FT
Benowitz
Neal L
NL
Bredt
Barry M
BM
Kosel
Bradley
B
Aberg
Judith A
JA
Deeks
Steven G
SG
Mitchell
Thomas F
TF
Mulligan
Kathleen
K
Bacchetti
Peter
P
McCune
Joseph M
JM
Schambelan
Morris
M
D000284:Administration, Oral; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D019888:Nelfinavir / Q000493:pharmacokinetics / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D002186:Cannabinoids; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D013759:Dronabinol; D019888:Nelfinavir