Antiretroviral Chemotherapeutic Agents: Preclinical Studies

  • Low Concentrations of Mycophenolic Acid Augment the Antiretroviral Activity of Abacavir (ABC), Didanosine (ddI), Tenofovir (TFV), and the Combination of ABC and ddI In Vitro (Poster 307)
    Authored by M. Hossain and D. Margolis
    View the original abstract

Mycophenolic acid (MPA) inhibits inosine monophosphate dehydrogenase and is active against HIV-1 in vitro. Reverse transcriptase inhibitors, such as dideoxyinosine and tenofovir, which are ultimately metabolized to adenosine analogs, are processed through the inosine pathways. MPA administration represents a possible way of augmenting the activity of these agents.

In this laboratory study, MPA was used at a range of doses (0-500 nM) which represent achievable serum concentrations. In combination with these NRTIs, both wild-type and resistant clones were inhibited in a dose-proportional manner. The use of MPA together with ddI and ABC demonstrated synergy. Neither the NRTIs nor MPA had an adverse effect on cell proliferation.

These data suggest that MPA may be a useful adjunct to therapy with ddI, abacavir and tenofovir at doses of MPA that do not induce immunosuppression, and is worthy of further clinical testing.