Mycophenolate Mofetil

Evidence Level: L5

Predicted Indications: 10

Mycophenolate Mofetil
Mycophenolate Mofetil: From Transplant Immunosuppression to HIV Infectious Disease

## Pharmacist Assessment Report

Mycophenolate Mofetil: From Transplant Immunosuppression to HIV Infectious Disease

One-Sentence Summary

Mycophenolate mofetil (MMF) is an immunosuppressant that inhibits lymphocyte proliferation, and it is marketed in Singapore under 11 licences (the approved indication text is not available in the data compiled for this report). The TxGNN model predicts it may be effective for HIV infectious disease, with 4 clinical trials (only 1 Phase 2 trial has completed, and its test agent was not MMF) and 20 publications on this topic. Evidence for this direction is limited and shows no clear virologic benefit.

Quick Overview

Item	Content
Original Indication	Not available (the approved indication text in the Singapore licences is empty)
Predicted New Indication	HIV infectious disease
TxGNN Prediction Score	99.86%
Evidence Level	L2 (as assessed in the compiled data; see the note under Clinical Trial Evidence)
Singapore Market Status	✓ Marketed
Number of Registrations	11
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data are not available in the data compiled for this report. Based on known pharmacology, MMF inhibits inosine monophosphate dehydrogenase (IMPDH), which depletes guanosine nucleotide pools. This reduces lymphocyte proliferation, which may limit the pool of activated CD4+ target cells for HIV. Depleted guanosine pools may also potentiate nucleoside analogue reverse transcriptase inhibitors such as abacavir and didanosine. A small study of 5 patients (PMID 12352149) reported depletion of intracellular dGTP and a decrease in plasma HIV-1 RNA when MMF was added to an abacavir-containing regimen.

The rationale is mechanistically plausible, but the clinical data are small and show no clear virologic benefit. Immunosuppression in people with HIV also raises safety concerns, so the benefit-risk balance is uncertain.

Other predictions in the list are weaker. Multiple sclerosis (score 99.54%) has Phase 2 and early-phase data, but these trials are small and the Cochrane reviews do not establish clear efficacy over established therapies. Most other predictions have no supporting trials or literature.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00038272	Phase 2	Completed	56	DAPD vs DAPD plus MMF added to anti-HIV regimens in treatment-experienced subjects. MMF was a combination arm, but the trial primarily tested DAPD
NCT01288131	Phase 3	Terminated	8	Cyclosporine plus MMF vs cyclophosphamide plus prednisolone in anti-rHuEpo-associated pure red cell aplasia. Link to HIV is unclear and not informative
NCT00112593	N/A	Completed	5	Non-myeloablative stem cell transplant in HIV-positive patients, with MMF as part of post-transplant immunosuppression. Not evidence of antiviral efficacy
NCT00021489	Phase 2	Withdrawn	0	Safety and antiretroviral activity of MMF added to abacavir in treatment-experienced HIV. Withdrawn before enrolment, so no data

Note on evidence level: The compiled data assign L2, but none of these trials provides direct, informative efficacy data for MMF in HIV. The only directly relevant trial was withdrawn, and the completed Phase 2 trial focused on a different agent. In practice the evidence is weaker than L2 suggests.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15353978	2004	RCT	AIDS	Effect of MMF added to HAART on HIV-1 RNA decay and latent cellular reservoir in treatment-naive patients
15871638	2005	Cohort	Clinical Pharmacokinetics	Pharmacokinetics and pharmacodynamics of low-dose MMF with abacavir, efavirenz and nelfinavir; monitoring recommended
16379601	2005	Cohort	AIDS Research and Human Retroviruses	No detrimental immunological effects of MMF plus HAART on T cell proliferation in treatment-naive patients
12352149	2002	Pilot study	J Acquir Immune Defic Syndr	MMF added to abacavir-containing regimens in 5 patients failing therapy: dGTP depletion and plasma HIV-1 RNA decrease
17017956	2006	Review	Current Topics in Medicinal Chemistry	Immunosuppressive drugs targeting immune activation in HIV disease
16515490	2006	Review	Current Pharmaceutical Design	Virostatics as a strategy to target HIV infection
20840478	2010	Retrospective study	American Journal of Transplantation	Kidney transplantation in 27 HIV-infected patients using MMF-based immunosuppression
23622672	2013	Cohort and review	Transplantation Proceedings	Renal transplantation in HIV-infected patients in Spain
41118390	2025	Preclinical	J Clin Invest	Selective targeting of HIV-infected T cell clones by antiproliferative drugs
19112763	2008	Case report	J Drugs Dermatol	Psoriasis and psoriatic arthritis in an HIV patient treated safely and effectively with MMF

Singapore Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
SIN09279P	CellCept Capsule 250 mg	Capsule	Not available
SIN10032P	CellCept Tablet 500 mg	Film-coated tablet	Not available
SIN11328P	CellCept for I.V. Infusion 500 mg/vial	Powder for solution for injection	Not available
SIN13986P	Myfenax Film-Coated Tablets 500 mg	Film-coated tablet	Not available
SIN15596P	Mycofit 250 Capsule 250 mg	Gelatin-coated capsule	Not available

All 11 licences are valid single-ingredient products. Oral (capsule and tablet) and injectable forms are available.

Safety Considerations

Contraindication-related associations from the knowledge graph (not label text): The TxGNN knowledge graph links MMF to contraindications including neutropenia, agranulocytosis, aplastic anaemia and related marrow failure syndromes, cytomegalovirus infection, herpes simplex and herpes zoster, progressive multifocal leukoencephalopathy, lymphoma, skin cancer and other cancers, active peptic ulcer disease, and liver and gallbladder disease. These associations are especially relevant in HIV, where opportunistic infections and cytopenias are already concerns.

Drug Interactions: 92 interactions were identified in total. Examples:

Major: Activated charcoal
Moderate: Proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole), antibiotics (amoxicillin, doxycycline, tetracycline, minocycline, clarithromycin, vancomycin, kanamycin, paromomycin), and antacids (magnesium oxide, aluminium hydroxide, calcium carbonate)
Minor: Zinc sulfate, zinc acetate, iron

Antiretroviral interactions were not specifically listed in the interactions shown, and should be checked before any HIV use.

Please refer to the package insert for label warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The mechanistic link (IMPDH inhibition and potentiation of nucleoside analogues) is plausible, but the clinical data are small, the only directly relevant trial was withdrawn, and no clear virologic benefit has been shown. Immunosuppression in HIV carries safety concerns, and the Singapore licence indication text and package insert safety data are missing.

To proceed, the following is needed:

Package insert warnings and contraindications from the HSA, and the approved indication text
Detailed mechanism of action data
Review of the randomized evidence (PMID 15353978) and any newer controlled data on virologic and reservoir outcomes
Assessment of interactions with current antiretroviral regimens and infection risk in people with HIV
Consideration of multiple sclerosis as an alternative lead, since it has Phase 2 data, while recognising that existing reviews do not show clear superiority over established therapies
Disclaimer

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