BUSPIRONE, A SEROTONIN RECEPTOR AGONIST, INCREASES CD4 T-CELL COUNTS AND MODULATES THE IMMUNE-SYSTEM IN HIV-SEROPOSITIVE SUBJECTS

Objective: We have previously shown that drugs that decrease intracell ular cAMP levels increase/restore the proliferative and cytotoxic capa city of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP le vels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro. Design: Buspirone was given as a single high dose to six HIV-seroposi tive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300x10(6)/l. Results: Significant increases in CD4 T cells, CD4 pe rcentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a signi ficant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of busp irone was administered. With continuous administration of buspirone, p lasma HIV RNA first increased within the first 2 weeks of treatment an d then decreased towards and below baseline concurrently with a signif icant decrease in CD8 T cells. The proliferative T-cell response to po ke weed mitogen and membrane expression of IL-2R increased significant ly during continuous treatment with a significant decrease in expressi on of HLA-DR on CD8+ T cells. Development of 'flu-like symptoms, so se vere that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of th e immune system by buspirone. Conclusion: The study shows that buspiro ne modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity cell maturation and viral load.