AIDS TREATMENT NEWS No. 079 - May 15, 1989
John S. James

The drug, dipyridamole (abbreviated DPMQthe brand name is Persantine) had little or no antiviral effect by itself. But in laboratory tests, it allowed AZT concentrations to be reduced by a factor of five to ten times and still have the same anti-HIV activity as the larger amount of AZT without the DPM. The concen- tration of DPM needed to achieve this effect was greater than or equal to two micromoles; usual oral doses of 100 to 400 mg per day produce blood levels of two to six micromoles, suggesting that such doses would likely be effective.

These tests were done in human macrophages, which are believed to be the major reservoir of HIV. DPM also enhanced the anti-HIV effect of DDC, an experimental antiviral in the same class as AZT, in macrophages.

The researchers discovered this effect of DPM by chance. They do not know why it occurred, but suspect that the mechanism may be one which would apply only to nucleoside analogs (such as AZT, DDC, or DDI), not to other kinds of antivirals.

DPM is an old, well-known drug and generally considered safe. We checked medical reference books and found no indication of serious toxicities when the drug is taken by mouth (toxicity from larger intravenous doses has been reported). According to the Physician's Desk Reference, there are no known contraindica- tions; only a few precautions are listed. Adverse reactions "are usually minimal and transient"; side effects generally disappear with long-term use. However, as far as we know the drug has never been tested with persons with HIV, and there may be need for special precautions. For example, since DPM works as an anticoagulant by inhibiting the action of platelets, it could be dangerous for persons with low platelet counts; a hematologist we spoke to was very concerned about this risk. Physicians will need to weigh potential risks and benefits.

According to a May 15 report in the San Francisco Chronicle, DPM has already been reviewed by a committee at the U. S. National Institute of Allergy and Infectious Diseases (NIAID), and plans are being developed for a clinical trial combining DPM and AZT, although no date for the trial has yet been set. Trials are necessary because the laboratory results do not prove that the drug will be useful against AIDS, or even safe when combined with AZT.

DPM should not be confused with heparin or dextran sulfate, which are also anticoagulants. DPM is different in that it is not an antiviral by itself.

Comment

We see these laboratory findings as especially important because of the ease with which this potential treatment can be tested, and if found to be useful, made widely available. Physi- cians can legally prescribe DPM for any use, although understand- ably they may be reluctant to do so, since as of this date the drug may never have been tried in patients for the purpose of enhancing AZT. DPM costs littleQabout 50 cents a day or less in its generic versionsQso cost will seldom be an obstacle to avai- lability.

We are concerned that trials will take too long, either because of bureaucracy before they even start, or because of inherently slow designs, such as having to wait for opportunistic infections or deaths (in an AZT-plus-placebo group) to gain irre- futable statistical proof of efficacy. Much faster trials are possible, for example looking for clear benefit from giving DPM to persons who are already taking AZT but not getting enough results from it.

Since many people cannot wait for trials to be completed, it seems inevitable that some patients and physicians will try DPM in combination with AZT; if they get good results, more will fol- low. Community-based or other research organizations could per- form an important service by monitoring and documenting the results of any such use.

The example of DPM illustrates one of the major although largely unrecognized public policy problems in the management of research on AIDS and other diseasesQthe lack of any institutional advocacy for the interests of patients in getting treatment sooner. The FDA and the NIH do not do this job; neither do drug companies, medical associations, most physicians, universities, foundations, or AIDS service organizations. It is tragic that in a major emergency we have had to take the time to develop new organizations (such as ACT UP) from scratch, because existing institutions have refused to become involved.

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