Mycophenolic Acid (MPA) is a compound that has been widely used to prevent transplant rejection in non-HIV+ patients. It appears to work by blocking the activity of an enzyme that is necessary for the production of a key component of DNA; in this respect it seems to be similar to Hydroxyurea. MPA reduces the production of a DNA "building block" called guanosine monophosphate. Abacavir (ABC), a nucleoside reverse transcriptase inhibitor that is one of the newer anti-HIV drugs, is chemically similar to guanosine monophosphate. If MPA could reduce the amount of the "normal" building block (guanosine monophosphate) in the body, than more of the Abacavir might be used instead, which might make Abacavir work better against HIV. The investigators in this report found that combining these two drugs seemed to be safe and effective in initial laboratory studies, and that they work synergistically (i.e., more effective together than the sum of their individual effects.).

The study looked at several viral strains of HIV, and found about an 8-fold synergistic effect of the combination of Abacavir and MPA when compared to Abacavir alone. MPA may also have a direct effect on inhibiting HIV itself, in addition to the effect on decreasing guanosine monophosphate.

Can MPA be used with drugs other than Abacavir? The study looked for an interaction with other NRTI's, and found that MPA is synergistic with ddI (about 2-fold). They found only additive anti-viral effects with 3TC and ddC (no synergy). Importantly, there was antagonism with both AZT and d4T, so these two drugs should not be used with MPA.

In conclusion, the findings were:

1. MPA has synergistic effects with Abacavir, and to a lesser extent with ddI.

2. MPA may be useful even in virus strains that have some resistance to Abacavir.

3. There were no synergistic toxicities (no increased unexpected side effects).

4. Antagonism was seen with d4T and AZT, so it probably isn't a good idea to use with these.

5. MPA is a promising compound that needs further study in combination with Abacavir and other drugs of the NRTI class.

It should be emphasized that the above studies were done in laboratory specimens, not in actual patients, and that controlled clinical trials to show benefit have not yet been performed.