Mycophenylate -- A Potential New Option
Mycophenylate (CellCept®) is an available prescription drug that may enhance the anti-HIV activity of abacavir (Ziagen®). Most data so far come from lab studies published by David Margolis and Robert Redfield of the Institute for Human Virology (headed by Robert Gallo). The team also has started human studies.
Mycophenylate is normally used to prevent rejection of kidney transplants. Mycophenylate suppresses production of guanosine, a key building block of DNA critical to the reproduction of HIV. Researchers reasoned that the drug would be most effective if paired with an antiviral that produced "false building blocks" resembling guanosine. They realized this meant abacavir, which mimics guanosine.
This model is similar to what happens when combining hydroxyurea with ddI, though studies suggest the mycophenylate/abacavir combination may be more potent and less toxic. More importantly, lab studies show the combination is highly active when used against abacavir-resistant virus.
A key question is whether the combination adds unacceptable toxicity or immune suppression, sometimes a problem with hydroxyurea + ddI. Based on lab data, however, it appears mycophenlyate can be used at doses two to ten times lower than those employed in normal application and still achieve high level anti-HIV effects.
These observations need to be confirmed in human studies, and the first have already begun. The simple two-drug combination is being given to advanced-stage patients who have failed all other therapies. Dosing employs 250mg of mycophenylate twice daily with the standard abacavir dose. The current dose of mycophenylate was chosen largely for convenience and lower doses may be tried in the future.
It is too early to recommend this for common use, but it builds upon a proven model and offers hope of a better treatment than hydroxyurea + ddI. Mycophenylate also has activity against hepatitis C virus and should also combine well with ribavirin, which is currently used in the treatment of hepatitis C. Mycophenylate should not be used with AZT or d4T as it is likely to negatively effect the activity of those drugs.
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