Effect of the serotonin receptor agonist, buspirone, on immune function in HIV-infected individuals: a six-month randomized, double-blind, placebo-controlled trial.
OBJECTIVE
Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load, and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals.


METHODS
Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the study. Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study.


RESULTS
A significant decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p =.0003) in buspirone-treated patients compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load, or proliferative response to PWM between those receiving placebo and those receiving buspirone.


CONCLUSIONS
Buspirone treatment leads to significant changes in CD8 T-cell count and in CD4/CD8 ratio. Thus, agents affecting the adenosine 3', 5'-cyclic monophosphate/protein kinase A type 1 (cAMP/PKA-1) pathway may be candidates for positive immune modulation in patients with HIV-1 infection.
Eugen-Olsen
J
J
Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark.
Benfield
T
T
Axen
T E
TE
Parner
J
J
Iversen
J
J
Pedersen
C
C
Nielsen
J O
JO
D000328:Adult; D002065:Buspirone / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D017366:Serotonin Receptor Agonists; D002065:Buspirone