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Dose proportional inhibition of HIV-1 replication by mycophenolic acid and synergistic inhibition in combination with abacavir, didanosine, and tenofovir.

Abstract：

:Mycophenolate mofetil (MMF), a therapeutically used inhibitor of inosine monophosphate dehydrogenase is hydrolyzed to its active metabolite mycophenolic acid (MPA) in vivo. MPA exhibits anti-HIV activity in vitro. We tested MPA alone and in combination with abacavir (ABC), didanosine (DDI), lamivudine (3TC) and tenofovir (TFV) against wild-type human immunodeficiency virus type-1 (HIV-1) and nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV-1. MPA (62.5-500 nM), when combined with ABC or DDI, synergistically enhanced activity against wild-type HIV and the NRTI-resistant HIV clone DRSM34. MPA also enhanced the activity of TFV against both wild-type HXB2 and TFV-resistant strain HIV(K65R), in a more than additive manner. No significant antiproliferative effect of MPA (< or =0.25 microM) alone or in the presence of ABC, DDI and TFV was observed. This indicates that the antiviral effects of MMF may be clinically achievable without fully blocking T-cell proliferation or inducing immunosuppression. These findings provide further rationale for the clinical testing of MMF in combination with ABC, DDI, and TFV.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Hossain MM,Coull JJ,Drusano GL,Margolis DM

doi

10.1016/s0166-3542(02)00006-2

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

41-52

issue

1

eissn

0166-3542

issn

1872-9096

pii

S0166354202000062

journal_volume

55

pub_type

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