Table 4.

Clinical studies regarding antiviral activities of DMARDs and immunosuppressants.

Medications	Viral susceptibility	In vitro	Animal study	Clinical report
Chloroquine HCQ	SARS-CoV	Freund et al.,30 Keyaerts et al.,31 Vincent et al.32
	HIV	✓ Savarino et al.,33 Boelaert et al.34		✓ RCT (n = 40): moderate efficacy35 ✓ Cohort (n = 287): decreased HIV vertical transmission36 ✓ RCT (n = 12): reduced T-cell immune activation; no effect on viral load37 ✓ Prospective (n = 20): significant reduction immune activation38 ✗ RCT (n = 83): no efficacy39 ✗ Single-arm, pilot (n = 20): not beneficial40
	Dengue virus	✓ Farias et al.41	✓ Farias et al.42	✓ RCT (n = 37): improve dengue-related symptoms43 ✗ RCT (n = 307): reduced fever period; no efficacy44
	Chikungunya virus	✓ Kaur and Chu45		✓ Open pilot study (n = 10): 50% improved clinically46 ✗ RCT (n = 54): no significant decrease in viremia47
	Influenza A virus	✓ Fedson48	✓ Yan et al.49	✓ Prospective study (n = 555): beneficial50 ✗ RCT (n = 1496): no preventive effect51
	HCV	✓ Ashfaq et al.52		✓ n = 1: 42 years, male with liver transplantation; PCT improved53
	Zika virus	✓ Li et al.54	✓ Li et al.54
Cyclosporine A	HIV	✓ Thali et al.55		✓ Retrospective study (n = 27): effective56 ✗ RCT (n = 28): no benefits under low-dose CsA57
	HCV genotype 1	✓ Liu et al.,58 Watashi et al.59		✓ Placebo-controlled trial (n = 120): increased sustained virological response60
	Flavivirus (Zika virus, Dengue virus, West Nile virus, Yellow fever virus)	✓ Qing et al.,61 Barrows et al.62
	Betaretrovirus	✓ Montano-Loza et al.63
Hydroxyurea	HIV	✓ Lori and Lisziewicz64		✓ RCT (n = 57): greater decrease in viral load65 ✓ RCT (n = 144): greater decrease of HIV RNA levels66 ✓ RCT (n = 69): higher rate reached HIV RNA level <200 and <2067 ✓ RCT (n = 134): greater decrease of HIV RNA levels68 ✓ RCT (n = 21): HIV RNA significant decrease, but no added benefit compared with placebo active comparator69
	HCV	✓ Nozaki et al.70		✓ phase I (n = 9): 8 people achieved moderate decrease in serum HCV RNA levels71
	HBV			✓ n = 4: significant decrease of viral loads in all patients72 ✗ n = 1, HBV reactivation73
	HSV	✓ Rosenkranz and Becker,74 Sergerie and Boivin75
	Parvovirus B19	✓ Bonvicini et al.76		✓ Retrospective review (n = 120): require fewer transfusions; higher nadir Hb concentration77
Minocycline	HIV	✓ Si et al.78	✓ Less degeneration of axons and less CNS replication of virus 79	✗ RCT (n = 107): no difference in cognitive function80 ✗ RCT (n = 73): no difference in cognitive function81
	Japanese encephalitis virus	✓ Mishra and Basu82	✓ Reduce viral titers, neuronal apoptosis83	✓ RCT (n = 44), 1–13 years: duration of fever, unconsciousness, and hospital stay significantly reduced; mortality rate unchanged84 ✓ RCT (n = 281): a trend towards better outcomes85
	Dengue virus	✓ Leela et al.86
	RSV	✓ Bawage et al.87
	Enterovirus 71	✓ Liao et al.88	✓ Decrease mortality rates, clinical scores, viral titers68
	Influenza virus	✓ Josset et al.89
	West Nile virus	✓ Michaelis et al.90
	Reovirus		✓ Delay encephalitis onset; reduce mortality91
	Rabies		✗ Worse, higher mortality rate92
Mycophenolate mofetil/Mycophenolic acid	HIV	✓ Chapuis et al.93	✓ Inhibition of virus isolation from purified CD4+ T-cell populations.93	✓ RCT (n = 17): combine MMF and HAART delayed viral load rebound and improved control of viral replication26
	Influenza virus	✓ To et al.27	✓ All mice survived; viral titers in lungs markedly reduced94
	MERS-CoV	✓ Chan et al.95	✗ Severe and fatal disease; higher viral loads than the untreated animals96
Leflunomide	HSV	✓ Knight et al.97		✓ n = 1: 42 years, male with HIV98 ✓ n = 1: 52 years, male with HIV99
	HIV	✓ Hossain and Margolis,100 Schlapfer et al.101		✓ RCT (n = 18): stable CD4+ T-cell counts102
	Molluscum and verruca			✓ n = 3 with AD103 ✓ n = 3 with renal transplantation104
	CMV	✓ Chacko and John105	✓ Chong et al.106	✓ Review (n = 45): viremia clearance in 73% of patients107
	BK virus			✓ Phase II RCT (n = 46): viremia decreased, no improvement of renal function108
	RSV	✓ Dunn et al.109	✓ Viral loads reduced109
Tofacitinib	HTLV-1		✓ Prolong survival duration110
Thalidomide	HHV-8			✓ Phase II (n = 17): 35% partial response rate111 ✓ Phase II (n = 20): 40% partial responses and 10% stable disease112

AD, atopic dermatitis; CMV, cytomegalovirus; CsA, cyclosporine A; DENV, dengue virus; DMARDs, disease-modifying anti-rheumatic drugs; HAART, highly active antiretroviral therapy; Hb, hemoglobin; HBV, hepatitis B virus; HCQ, hydroxychloroquine; HCV, hepatitis C virus; HHV-8, human herpesvirus 8; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV-I, human T cell lymphotrophic virus-1; MERS-CoV, Middle East respiratory syndrome coronavirus; MMF, mycophenolate mofetil; PCT, porphyria cutanea tarda; RCT, randomized-controlled trial; RSV, respiratory syncytial virus; RNA, ribonucleic acid; SARS-CoV, severe acute respiratory syndrome coronavirus.