Human Polyomavirus Reactivation: Disease Pathogenesis and Treatment Approaches

Table 2

Antiviral therapies for human polyomavirus infection.

Antiviral agent	Mechanism of action	HPyV	In vitro; activity	Clinical syndrome	Study design	Patient group	Clinical benefit	References
				—	—	—	—	[274]
Cytosine arabinoside; (Ara-C)	Nucleoside analogue; (DNA polymerase inhibitor)	JCV	Yes	PML	Case series/reports	HIV, non-HIV, dermatomyositis	Yes	[282–285]
				PML	Case series/reports	HIV, non-HIV, dermatomyositis	No	[282, 286–289]
				PML	RCT	HIV	No	[290]
				—	—	—	—	[274]
				PML	Pilot study	HIV	No	[281]
		JCV	No	PML	Multicohort analysis	HIV	No	[279]
				PML	Multicentre Retrospective analysis	HIV	No	[278]
Cidofovir; (CDV)	Nucleotide phosphonate analogue (DNA polymerase inhibitor)			PML	Case series	HIV	No	[280]
				PML	Case reports	HIV, the Heerfordt syndrome, SLE	Yes	[275–277]
				—	—	—	—	[291]
		BKV	Yes	HC	Case series	HSCT	Yes	[292]
				BKVN	Nonrandomised Controlled study (low-dose CDV)	Renal T’plant	Yes	[293]
		TSV	N/A	TS	Case report	Heart T’plant, CLL	Yes	[6, 294]
		JCV	Yes	—	—	—	—	[295, 296]
				PML	Case report	Idiopathic CD4+ lymphocytopaenia	Yes	[297]
CMX001	Lipid conjugate of Cidofovir
		BKV	Yes	—	—	—	—	[291]
				BK Viruria	RCT	Renal T’plant	Pending	ClinicalTrials.gov-NCT00793598
				—	—	—	—	[298, 299]
				PML	Case report (mirtazapine)	Dermatomyositis	Yes	[285]
Serotonin receptor 2A (5HT2AR) antagonists	Inhibits JCV receptor binding and cell entry	JCV	Yes	PML	Case report; (mirtazapine)	HIV	Yes	[300]
				PML	Case report; (chlorpromazine)	CLL/HSCT	No	[301]
Mefloquine	Unknown: may directly inhibit large T antigen	JCV	Yes	—	—	—	—	[302]
				PML	Case report	Sarcoidosis, AML/UBCT	Yes	[303, 304]
				PML	RCT	HIV	No	[23]
Leflunomide	Inhibits pyrimidine synthesis; inhibits tyrosine kinase	BKV	Yes	—	—	—	—	[305, 306]
				BKVN	Case series	Renal T’plant	Yes	[307]
				BKVN	Case series	Renal T’plant	No	[308]
				BKVN	Case series	Renal T’plant	No	[309]
FK778	Derived from the active metabolite of Leflunomide			BKVN	RCT	Renal T’plant	No	[310]
Fluoroquinolones	Inhibit large T antigen helicase activity	BKV	Yes	—	—	—	—	[311, 312]
				BK viraemia	Case series	Renal T’plant	Yes	[313]
						Renal T’plant	Yes; (3 mo.)	[314]
							No; (12 mo.)	[314]
				HC	Case series	HSCT	Yes	[315]
Mammalian target of rapamycin (mTOR) inhibitors	Reduce translation and; cell cycle progression	BKV	Yes (sirolimus)	—	—	—	—	[316]
				BKVN	Case series	Renal T’plant	Yes	[317]
				BKVN	Case report	Renal T’plant	No	[199]
				BK viraemia	Prospective Nonrandomised controlled study	Renal T’plant (Paediatric)	No	[318]

This table lists the available therapeutic options for human polyomavirus infections. KIPyV, WUPyV, HPyV6, 7, 9, and 10 have not been included as there are presently no definitive disease associations for these viruses. Abbreviations are defined in the accompanying text.