Immune-Based Therapy

• Mycophenolate Mofetil (MMF) Induces a Decrease in HIV-1 RNA Associated with Guanosine Depletion (Poster 351)
  Authored by D. Margolis, M. Hossain, L. Shaw, and D. Back
  View the original abstract

Mycophenolic acid (MA) is a selective inhibitor of lymphocyte proliferation, which inhibits inosine monophosphate dehydrogenase, blocking the synthesis of guanosine monophosphate, and increasing the affinity of reverse transcriptase for triphosphorilated nucleoside analogs.

This study is part II of the poster I discussed yesterday (see Coull et al., abstract 56).

It is not completely clear what is the exact mechanism that makes mycophenolic acid work. In this small pilot trial, David Margolis tries to characterize carefully the most likely mechanism. The trial involved only four patients who used mycophenolic acid, and the small size of this trial is its main limitation. Two of the patients took mycophenolic acid as a part of a dose escalation from lower mycophenolic acid doses of 250mg BID, and the other two patients started directly at a higher 500mg BID dose.

There was a transient drop in viral load, similar to the one I discussed yesterday and a transient decrease in dGTP. The decrease in dGTP was associated with the decay in viral load, which suggests that this is the mechanism that mediates mycophenolic acid activity as an antiretroviral agent.

Over time there was a decrease in the mycophenolic acid levels, which also suggests that there might be a problem with PK or metabolic induction of the metabolism of this drug, although the study is too small to make firm conclusions. Alternatively, it could be related to problems with adherence over time. The CD4 cell count remained stable, confirming the results of the previous, a little bit larger, cohort.

As I said in my previous summary, we need to define the role of mycophenolic acid in the management of HIV infection. Prospective randomized trials will provide the answers to the questions that need to be asked. I have the suspicion that we will hear more about this drug in the next Retrovirus Conference.