Background: The immunosuppressant mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA), a selective and reversible inhibitor of the de novo synthesis of the purine guanosine in lymphocytes. MMF has been proposed for HIV therapy, since it is expected to prevent HIV replication and decrease the HIV cellular reservoir directly and indirectly via inhibition of CD4⁺ T-cell division. However, MMF might also induce hematological toxicity and affect thymic function, with the risk of slowing down or preventing immune reconstitution.

Methods: Here we studied the immunological effects of treatment with MMF in combination with HAART (consisting of didanosine, lamivudine, abacavir, nevirapine, indinavir, and low dose ritonavir) in 3 chronic and 3 acute HIV-1 infected, treatment naïve patients (pts) compared to 4 controls for each group treated with HAART alone for a period of 20–48 weeks.

Results: Stimulation of T-cells in whole blood cultures revealed near complete inhibition of thymidine incorporation in pts treated with MMF as compared to controls. Strikingly, proliferation of naïve, memory and effector CD4⁺ and CD8⁺ T-cells when measured by Ki67 expression ex vivo was not influenced by MMF. However, in vitro studies showed that Ki67 expression occurs at an early step of the cell cycle not inhibited by MMF. Absolute numbers of naïve CD4⁺ and CD8⁺ T cells, as well as the number of TRECs in CD4⁺ and CD8⁺ T-lymphocytes and apoptosis were not different in pts treated with MMF. Percentages of HIV-specific CD8⁺ T-cells and HIV-specific IFNγ production by CD8⁺ T-cells were not changed by MMF. Furthermore, MMF did not affect HIV-specific IFNγ production by CD4⁺ lymphocytes, nor did MMF change HIV- specific IL2 production by CD4⁺ T-cells in chronic infection. However, in acute HIV pts treated with MMF, a lower percentage of IL2 producing CD4⁺ T-cells was observed.

Conclusions: Our data show that MMF, when administered in combination with HAART, did not seem to affect immune reconstitution in pts on HAART.