Mycophenolate Mofetil

證據等級: L5

預測適應症: 10 個

Mycophenolate Mofetil: From Organ Transplant Rejection Prevention to HIV Infectious Disease

One-Sentence Summary

Mycophenolate mofetil (MMF) is a purine-synthesis-inhibiting immunosuppressant established for preventing organ transplant rejection. The TxGNN model predicts it may be effective for HIV Infectious Disease, with 10 clinical trials and 20 publications currently identified as supporting evidence, though several trials were withdrawn or have unreported outcomes.

Quick Overview

Item	Content
Original Indication	Prevention of organ transplant rejection (kidney/heart/liver) — based on established pharmacological knowledge; not present in this evidence pack’s TFDA license data (0 licenses on file)
Predicted New Indication	HIV Infectious Disease
TxGNN Prediction Score	99.86%
Evidence Level	L3
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, DrugBank-sourced mechanism-of-action data for this drug is marked as a data gap. Based on the mechanistic rationale available in the predictions, MMF is an inosine monophosphate dehydrogenase (IMPDH) inhibitor that blocks de novo purine synthesis, suppressing proliferation of activated T and B lymphocytes. This is the same mechanism that underlies its proven efficacy in preventing transplant rejection.

In HIV infection, activated CD4+ T cells are both the primary viral target and the main driver of the latent reservoir. The “virostatic” hypothesis proposes that limiting proliferation of these activated cells with MMF could reduce viral target-cell availability and reservoir expansion. Several early studies also report a pharmacodynamic synergy between MMF and abacavir, with MMF depleting intracellular dGTP pools that potentiate abacavir’s antiviral activity.

However, this mechanism is inherently double-edged in HIV: immunosuppression that reduces T-cell proliferation could also impair immune reconstitution and increase susceptibility to opportunistic infection in an already immunocompromised population. This tension is reflected in the trial evidence below, where several MMF-HIV studies were withdrawn or terminated, and no completed trial demonstrates a definitive clinical benefit.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00021489	Phase 1/2	Withdrawn	0	Designed to assess MMF safety/tolerability and antiretroviral activity added to abacavir in treatment-experienced HIV patients; withdrawn, no results
NCT00247494	Phase 4	Unknown	90	MAN2 substudy evaluating MMF’s effect on cardiovascular surrogate markers in HIV-1 patients; outcome status unconfirmed
NCT00120419	Phase 4	Unknown	90	MAN2 study: MMF in ART-naive chronically HIV-1-infected patients, assessing immune hyperactivation, CD4+ decline, and plasma HIV-1 RNA; outcome status unconfirmed
NCT00112593	N/A	Completed	5	Allogeneic HSCT with fludarabine/TBI plus cyclosporine and MMF for HIV-positive patients (with/without cancer)
NCT00038272	Phase 2	Completed	56	Randomized, double-blind pilot comparing DAPD vs. DAPD+MMF in treatment-experienced HIV subjects
NCT00009009	Phase 2	Completed	10	Renal transplantation safety/efficacy in HIV-infected patients with end-stage renal disease; MMF used as standard post-transplant immunosuppression
NCT02793544	Phase 2	Completed	80	HLA-mismatched unrelated donor BMT with post-transplant cyclophosphamide; MMF used for GVHD prophylaxis in hematologic malignancy, not HIV-specific
NCT01453192	Phase 3	Completed	27	Clinical/immunological follow-up after renal transplantation in HIV-1-infected patients on antiretroviral regimens including raltegravir
NCT01288131	Phase 3	Terminated	8	Cyclosporine+MMF vs. cyclophosphamide+prednisolone for anti-r-HuEpo-associated PRCA; not an HIV indication trial
NCT06869265	Phase 2	Recruiting	56	TBF conditioning for haploidentical HSCT in elderly high-risk AML; not an HIV indication trial

Literature Evidence

PMID	Year	Type	Journal	Key Findings
12352149	2002	Clinical study	J Acquir Immune Defic Syndr	Adding MMF to abacavir-containing ART depleted intracellular dGTP and was associated with decreased plasma HIV-1 RNA in 5 heavily treated patients
15213566	2004	Randomized pilot study	J Acquir Immune Defic Syndr	MMF during HAART interruption in chronic HIV-1 infection; assessed immune response and viral load in lymphatic tissue
15353978	2004	Clinical trial	AIDS	HAART with or without MMF in treatment-naive HIV-1 patients; studied effect on plasma HIV-1 RNA decay and latent reservoir
16379601	2005	Cohort	AIDS Res Hum Retroviruses	No detrimental immunological effects observed with MMF plus HAART in treatment-naive acute/chronic HIV-1 patients
15871638	2005	Cohort/PK-PD study	Clin Pharmacokinet	Pharmacokinetics/pharmacodynamics of low-dose MMF combined with abacavir, efavirenz, and nelfinavir in HIV patients
15355127	2004	PK study	Clin Pharmacokinet	MMF’s effect on antiretroviral drug pharmacokinetics and intracellular nucleoside triphosphate pools
17885292	2007	Clinical trial	AIDS	Safety, tolerability, and antiretroviral activity of DAPD with or without MMF in drug-resistant HIV-1 infection
11391161	2001	Pilot study	J Acquir Immune Defic Syndr	Open-label pilot of MMF added to salvage ART (abacavir, ddI, amprenavir, ritonavir ± efavirenz) in multidrug-resistant HIV-1
17017956	2006	Review	Curr Top Med Chem	Reviews immunosuppressive drugs, including MMF, as adjunctive strategies targeting immune hyperactivation in HIV disease
41118390	2025	Mechanistic/translational study	J Clin Invest	Explores selective targeting of clonally expanded HIV-infected CD4+ T cells via antiproliferative drug susceptibility

US Market Information

This drug is currently recorded as not marketed in the reviewed regulatory jurisdiction, with 0 license records on file — no NDA/product-level detail is available in this evidence pack.

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug interaction data are marked as data gaps in this evidence pack; note that DG001 — missing TFDA label warnings/contraindications — is flagged as a Blocking severity gap that prevents completion of the initial safety screen (S1).)

Conclusion and Next Steps

Decision: Hold

Rationale: While the mechanistic rationale (IMPDH inhibition limiting activated CD4+ T-cell proliferation) is biologically plausible and supported by multiple early-phase and cohort studies, no completed trial demonstrates definitive clinical benefit — several key trials (NCT00021489, NCT00247494, NCT00120419) are withdrawn, terminated, or of unconfirmed outcome status. Critically, the Blocking data gap on TFDA label warnings/contraindications (DG001) prevents completion of even the initial safety screen for an immunosuppressant in an immunocompromised HIV population, where opportunistic infection risk is a major concern.

To proceed, the following is needed:

TFDA (or equivalent) package insert warnings and contraindications to complete the S1 safety screen
Formal DrugBank mechanism-of-action confirmation
Outcome data retrieval for the unknown-status MAN2 studies (NCT00247494, NCT00120419)
Drug interaction data, particularly with antiretroviral regimens
Updated literature/trial search to capture any post-2025 developments
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.