TreatmentUpdate 73 - Volume 8, No 9; November 1996
Sean Hosein

Long before the CD4+ (T4+) cell counts fall below the normal range in HIV-infected people, defects in the immune system's defences appear. One example of such a defect is that T cells may not detect and fight invading germs. One research team in Denmark has reported promising results when they tested an antidepressant in people with HIV infection.

Study details

Doctors recruited 10 symptom-free, HIV-infected subjects for this study. Initially the researchers interviewed 9 men and 2 women, but the gender of the person who did not receive the study drug is not clear. At least half the subjects had 214 CD4+ cells before receiving the antidepressant. Four subjects were receiving anti-HIV drugs while in the study (AZT or ddI), while 4 others were using the immune booster isoprinosine. In the first part of the study, 6 subjects received one dose of the antidepressant BuSpar 60 mg taken orally. In the second part of the study, between 11 to 18 weeks later, depending on the subject, doctors them gave longer courses of BuSpar. For the first 2 weeks the doctors gave subjects gradually increasing doses of the antidepressant, starting with 15 mg/day and up to 60 mg/day when possible. Subjects received daily doses of the drug for up to 6 weeks.

Results -- part 1

In the first part of the study where subjects received just one dose of BuSpar, 50% of them had their CD4+ cell count rise from 206 cells to 252 cells in one week. This increase was statistically significant; that is, likely due to BuSpar and not chance. Four weeks after taking just one dose of the drug, the CD4+ cell count fell to 238 cells.

Results -- part 2

In the second part of the study where subjects received BuSpar for 6 weeks, there were also statistically significant increases in CD4+ cell counts. However, the level of these cells did not rise steadily over the course of the study. Rather, they reached their peak at one and four weeks after subjects began using BuSpar every day. Some subjects had an increase of 16 cells, and others of about 100, compared to before they began using the drug.

Results -- other cells

CD8+ cell counts began to fall and reached "[near] normal values in the 2nd and 3rd week of the study [when BuSpar was taken daily]." This decrease in the CD8+ cell count was statistically significant. The ability of T cells to respond to germs increased, compared to their pre-study level and remained high even at the 7th week of the study when subjects were no longer taking the drug.

Results -- production of HIV

BuSpar did not appear to cause significant increases in the amount of HIV in the blood of subjects. After subjects took just one dose of BuSpar, the amount of HIV in the blood fell significantly -- to 1/10th of or less of the pre-study level. However, one day later the viral load returned to its pre-BuSpar level. During the part of the study where BuSpar was taken every day, levels of HIV in the blood rose "during the first two weeks." After that it fell below pre-study levels.

Toxicity

Side effects reported include:

* dizziness

* nausea

* "sleeping problems"

Two of 4 subjects had severe symptoms of a "flu-like [syndrome]" reporting:

* fatigue

* muscle pain

* "sweating"

* "low-grade fever"

These subjects left the study because of the severity of the symptoms.

Changes in the immune system

Results from this study suggest that BuSpar 60 mg/day can increase CD4+ cell counts, and over a period of 6 weeks, reduce the amount of HIV in the blood. During this time there was a decrease in the level of CD8+ cells. This decrease in the CD8+ cell count may or may not be useful. These cells can attack HIV-infected cells and over the long term, having fewer CD8+ cells could pose problems. However, during the first 2 to 3 weeks, as the CD8+ cell count fell, so did the amount of HIV in the blood. By the 5th week of the study, levels of CD4+ cells rose followed by an increase in the amount of HIV in the blood while CD8+ cell counts decreased. The study doctors plan to conduct a long term study comparing the effects of BuSpar against that of fake BuSpar (placebo).

REFERENCES:

1. Hofmann B, Afzelius P, Iversen J, et al. Buspirone, a serotonin receptor agonist, increases CD4+ T-cell counts and modulates the immune system in HIV-seropositive subjects. AIDS 1996;10(12):1339-1347.

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Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca