Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanos ine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrat e (guanosine nucleotides) for reverse transcriptase. Here we show that myco phenolic acid induced apoptosis and cell death in a large proportion of act ivated CD4(+) T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and Immunological mechanisms (depleti on of the pool of activated CD4(+) T lymphocytes). Administration of mycoph enolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4(+) and CD8(+) T ce lls and in the inhibition of virus isolation from purified CD4(+) T-cell po pulations. Based on these results, the potential use of mycophenolate mophe til in the treatment of HIV infection deserves further investigation in con trolled clinical trials.