Aspirin Update: Warning, Promise, and Call for Information

Last August 17, AIDS TREATMENT NEWS published an in-depth look at the possibility that ordinary aspirin might have a role in AIDS treatment -- as an immune modulator, not just for minor symptom relief. One of the physicians we interviewed, Joseph Sonnabend, M. D., in New York, called recently to warn us of the importance of medical monitoring with aspirin use -- especially the need to follow platelet count. He has seen one case of serious hemorrhage in a patient with a rapidly falling platelet count, who was taking two 325-mg aspirin tablets four times a day. Fortunately, this person recovered.

Dr. Sonnabend suggests that anyone with a platelet count of under 100,000, or who has ever had thrombocytopenia (low platelet count), should have frequent medical supervision if they use aspirin, or other drugs which can interfere with blood clotting. Anyone with HIV should be monitored by their physician if they use aspirin.

Background note: platelets assist in blood clotting. Platelet counts often decline in persons with HIV infection. For unknown reasons, this decline is usually less serious than if the same numbers occurred in persons without HIV -- and platelet counts often become normal again as HIV infection progresses. Bleeding problems due to low platelets have been rare with HIV infection; but the case mentioned above shows that risk does exist, and appropriate precautions are necessary.


A Report of T-Helper Improvement

We have heard of one case of an unexpected major improvement in T-helper count after low-dose aspirin use. We are reluctant to mention a single case until there is confirmation; but here, the patient was in an NIH epidemiological study and has very good data available -- quarterly T-helper and other blood counts from a quality- controlled lab for the last six years. We also chose to mention this case because it suggests that an easy-to-organize community-based trial could tell quickly if the effect is real, or just a chance result in one case.

This patient's T-helper count had declined for four years, then stabilized at an average of about 500 with AZT; he has taken 500 mg of AZT per day for two years. He started taking a single 325-mg buffered aspirin tablet per day near the end of August, 1990. His last T-helper count before starting aspirin was 553. By mid September the count was unchanged at 556, although the helper/suppressor ratio had changed from .56 to .78. By mid November the count was 895, and by mid December it was 968 (the November test was to apply for a different NIH study). The T- helper percent and helper/suppressor ratio showed substantial increases. There was no other change in therapy or other known factor which would explain these improvements.

The patient had selected the low dose (one aspirin a day) because of a report1 that an even lower dose (one aspirin every other day) had the greatest effect in increasing both interleukin-2 (IL-2) and interferon gamma in healthy volunteers. In this study, IL-2, which stimulates the growth of T-cells, was increased to two to three times baseline levels by low-dose aspirin.


Questions for a Clinical Trial

* The first question for a trial to answer is whether aspirin can have any consistent effect in raising T-helper counts, or if the effect reported above was just happenstance or only applied to one patient. Clearly it would be easy to run a trial with low- dose aspirin, and follow T-helper counts for at least three months.

Some other questions:

* Is antiviral therapy (in this case, AZT) necessary? Stimulating the growth of T-helper cells without antiviral therapy might increase the growth of the virus. We have heard good results from studies which combined IL-2 and AZT; one early report found a T-helper increase of over 300 during IL-2 therapy, although the increase disappeared after treatment was stopped2. (As we went to press, we learned that results of an important trial at Stanford University of combination HIV treatment with IL-2 and AZT have recently been published; we could not obtain this paper by press time.) If low-dose aspirin does indeed stimulate the body to produce more of its own IL- 21, then aspirin might be an alternative easier to obtain, safer, and of course less expensive than the experimental pharmaceutical IL-2.

* Could this treatment approach also work for persons with lower starting T-helper counts? A community-based trial could accept volunteers with a range of T-helper values. Then -- if any significant effect is seen -- the researchers could look for a dose- response relationship.


Call for Information

Any information about long-term use of aspirin, and its effect (or lack of effect) on T-helper counts, could be helpful for designing such a trial. If you have information we should know about, contact John S. James at AIDS TREATMENT NEWS.

References

1. Hsia J., Simon GL, Higgins N, Goldstein AL, and Hayden FG. Immune modulation by aspirin during experimental rhinovirus colds. Bulletin of the New York Academy of Medicine. January 1989; volume 65, number 1, pages 45-56. (Note: the data cited above was from volunteers who did not have colds.)

2. Bartlett JA, Blankenship K, Waskin H, Sebastian M, Shipp K, and Weinhold K. Zidovudine and interleukin-2 in WR2 HIV infected patients: Evidence for stimulated immunologic reactivity against HIV [abstract S. B. 421]. Sixth International Conference on AIDS, San Francisco, June 20-24, 1990.

Note: For background on aspirin, and what is known or not known about its different mechanisms of action, see the latest Scientific American, January 1991, pages 84-90.