Source: Springer Link


The process of finding new therapeutic indications for currently used drugs, defined as ‘repurposing’, is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple’s disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren’s syndrome), and other immunological diseases.

Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects. Among the biological effects of chloroquine and hydroxychloroquine, it is important to highlight their antitumoral properties, likely due to their strong antiproliferative, antimutagenic, and inhibiting autophagy capacities.

These effects make these drugs a possible option in the treatment of several tumors in association with radiotherapy and chemotherapy. Finally, the repurposing of chloroquine and hydroxychloroquine is currently being examined for neurological diseases such as neurosarcoidosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to corticosteroids, and primary progressive multiple sclerosis.

Several ongoing clinical trials have been testing these drugs in non-neoplastic and neoplastic diseases.

Moreover, the well-demonstrated good tolerability of chloroquine and hydroxychloroquine make them safe even during pregnancy.

Gastrointestinal and cutaneous manifestations are considered not to be serious, while retinal, neuromuscular, and cardiac toxicities are classified as serious adverse events.


1.Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3:673–83.PubMed Article CAS Google Scholar 

2.Vesterinen HM, Connick P, Irvine CMJ, Sena ES, Egan KJ, Carmichael GG, et al. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis. PLoS One. 2015;10:e0117705.PubMed PubMed Central Article CAS Google Scholar 

3.Al-Bari MAA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70:1608–21.PubMed Google Scholar 

4.Wallace DJ. Antimalarials—the “real” advance in lupus. Lupus. 2001;10:385–7.PubMed Article CAS Google Scholar 

5.Wallace DJ. The history of antimalarials. Lupus. 1996;5(Suppl 1):S2–3.PubMed Google Scholar 

6.Krafts K, Hempelmann E, Skórska-Stania A. From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy. Parasitol Res. 2012;111:1–6.PubMed Article Google Scholar 

7.Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012;42:145–53.PubMed Article CAS Google Scholar 

8.Smith CD, Cyr M. The history of lupus erythematosus. From Hippocrates to Osler. Rheum Dis Clin North Am. 1988;14:1–14.PubMed CAS Google Scholar 

9.Stoughton RB. Treatment of chronic lupus erythematosus with atabrine and chloroquine. Ill Med J. 1955;107:299–302.PubMed CAS Google Scholar 

10.Wallace DJ. The use of quinacrine (Atabrine) in rheumatic diseases: a reexamination. Semin Arthritis Rheum. 1989;18:282–96.PubMed Article CAS Google Scholar 

11.Conner SK. Systemic lupus erythematosus; a report on twelve cases treated with quinacrine (atabrine) and chloroquine (aralen). Ann Rheum Dis. 1957;16:76–81.PubMed PubMed Central Article CAS Google Scholar 

12.Farber EM, Driver IE. Atabrine and chloroquine in the treatment of chronic discoid lupus erythematosus. Stanford Med Bull. 1953;11:157–8.PubMed CAS Google Scholar 

13.Tye MJ, White H, Appel B, Ansell HB. Lupus erythematosus treated with a combination of quinacrine, hydroxychloroquine and chloroquine. N Engl J Med. 1959;260:63–6.PubMed Article CAS Google Scholar 

14.Goldman L, Cole DP, Preston RH. Chloroquine diphosphate in treatment of discoid lupus erythematosus. J Am Med Assoc. 1953;152:1428–9.PubMed Article CAS Google Scholar 

15.Rand JH, Wu X-X, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008;112:1687–95.PubMed PubMed Central Article CAS Google Scholar 

16.DrugBank. Chloroquine. Accessed 4 Mar 2016.

17.DrugBank. Hydroxychloroquine. Accessed 4 Mar 2016.

18.Kim K-A, Park J-Y, Lee J-S, Lim S. Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res. 2003;26:631–7.PubMed Article CAS Google Scholar 

19.Munster T, Gibbs JP, Shen D, Baethge BA, Botstein GR, Caldwell J, et al. Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum. 2002;46:1460–9.PubMed Article CAS Google Scholar 

20.Bernstein HN. Ocular safety of hydroxychloroquine. Ann Ophthalmol. 1991;23:292–6.PubMed CAS Google Scholar 

21.Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983;75:40–5.PubMed Article CAS Google Scholar 

22.Gustafsson LL, Lindström B, Grahnén A, Alván G. Chloroquine excretion following malaria prophylaxis. Br J Clin Pharmacol. 1987;24:221–4.PubMed PubMed Central Article CAS Google Scholar 

23.Chloroquine—FDA prescribing information, side effects and uses. Accessed 14 Apr 2018. Hydroxychloroquine uses, dosage and side effects. Accessed 14 Apr 2018.

25.McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983;75:11–8.PubMed Article CAS Google Scholar 

26.Durcan L, Clarke WA, Magder LS, Petri M, Hopkins J. Hydroxychloroquine blood levels in systemic lupus erythematosus: clarifying dosing controversies and improving adherence. J Rheum. 2015;42(11):2092–7. CAS Article Google Scholar 

27.Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69:20–8.PubMed Article CAS Google Scholar 

28.Sciascia S, Branch DW, Levy RA, Middeldorp S, Pavord S, Roccatello D, et al. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment. Thromb Haemost. 2016;115:285–90.PubMed Article Google Scholar 

29.Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016;214:273.e18.Article CAS Google Scholar 

30.Mekinian A, Lazzaroni MG, Kuzenko A, Alijotas-Reig J, Ruffatti A, Levy P, et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev. 2015;14:498–502.PubMed Article CAS Google Scholar 

31.Leroux M, Desveaux C, Parcevaux M, Julliac B, Gouyon JB, Dallay D, et al. Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study. Lupus. 2015;24:1384–91.PubMed Article CAS Google Scholar 

32.Koh JH, Ko HS, Kwok S-K, Ju JH, Park S-H. Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus. Lupus. 2015;24:210–7.PubMed Article CAS Google Scholar 

33.Clowse MEB, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006;54:3640–7.PubMed Article Google Scholar 

34.Luo Y, Zhang L, Fei Y, Li Y, Hao D, Liu Y, et al. Pregnancy outcome of 126 anti-SSA/Ro-positive patients during the past 24 years–a retrospective cohort study. Clin Rheumatol. 2015;34:1721–8.PubMed Article Google Scholar 

35.Kaufmann AM, Krise JP. Lysosomal sequestration of amine-containing drugs: analysis and therapeutic implications. J Pharm Sci. 2007;96:729–46.PubMed Article CAS Google Scholar 

36.Yoon YH, Cho KS, Hwang JJ, Lee S-J, Choi JA, Koh J-Y. Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells. Invest Ophthalmol Vis Sci. 2010;51:6030–7.PubMed Article Google Scholar 

37.Ziegler HK, Unanue ER. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci USA. 1982;79:175–8.PubMed Article CAS Google Scholar 

38.Costedoat-Chalumeau N, Dunogué B, Morel N, Le Guern V, Guettrot-Imbert G. Hydroxychloroquine: a multifaceted treatment in lupus. Presse Med. 2014;43:e167–80.PubMed Article Google Scholar 

39.Landewé RB, Miltenburg AM, Verdonk MJ, Verweij CL, Breedveld FC, Daha MR, et al. Chloroquine inhibits T cell proliferation by interfering with IL-2 production and responsiveness. Clin Exp Immunol. 1995;102:144–51.PubMed PubMed Central Article Google Scholar 

40.van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S, Verweij CL. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol. 1997;24:55–60.PubMed Google Scholar 

41.Picot S, Peyron F, Vuillez JP, Polack B, Ambroise-Thomas P. Chloroquine inhibits tumor necrosis factor production by human macrophages in vitro. J Infect Dis. 1991;164:830.PubMed Article CAS Google Scholar 

42.Jang C-H, Choi J-H, Byun M-S, Jue D-M. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford). 2006;45:703–10.Article CAS Google Scholar 

43.Sperber K, Quraishi H, Kalb TH, Panja A, Stecher V, Mayer L. Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells. J Rheumatol. 1993;20:803–8.PubMed CAS Google Scholar 

44.Ghigo D, Aldieri E, Todde R, Costamagna C, Garbarino G, Pescarmona G, et al. Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells. J Clin Invest. 1998;102:595–605.PubMed PubMed Central Article CAS Google Scholar 

45.Lafyatis R, York M, Marshak-Rothstein A. Antimalarial agents: closing the gate on toll-like receptors? Arthritis Rheum. 2006;54:3068–70.PubMed Article CAS Google Scholar 

46.Wellems TE, Plowe CV. Chloroquine-resistant malaria. J Infect Dis. 2001;184:770–6.PubMed Article CAS Google Scholar 

47.Cui L, Mharakurwa S, Ndiaye D, Rathod PK, Rosenthal PJ. Antimalarial drug resistance: literature review and activities and findings of the ICEMR Network. Am J Trop Med Hyg. 2015;93:57–68.PubMed PubMed Central Article CAS Google Scholar 

48.Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M, et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother. 2009;53:3416–21.PubMed PubMed Central Article CAS Google Scholar 

49.Farias KJS, Machado PRL, Muniz JAPC, Imbeloni AA, da Fonseca BAL. Antiviral activity of chloroquine against dengue virus type 2 replication in Aotus monkeys. Viral Immunol. 2015;28:161–9.PubMed PubMed Central Article CAS Google Scholar 

50.Borges MC, Castro LA, de Fonseca BAL. Chloroquine use improves dengue-related symptoms. Mem Inst Oswaldo Cruz. 2013;108:596–9.PubMed PubMed Central Article CAS Google Scholar 

51.Wang L-F, Lin Y-S, Huang N-C, Yu C-Y, Tsai W-L, Chen J-J, et al. Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015;35:143–56.PubMed PubMed Central Article CAS Google Scholar 

52.Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis. 2003;3:722–7.PubMed Article CAS Google Scholar 

53.Kersh GJ. Antimicrobial therapies for Q fever. Expert Rev Anti Infect Ther. 2013;11:1207–14.PubMed PubMed Central Article CAS Google Scholar 

54.Dey S, Bishayi B. Killing of Staphylococcus aureus in murine macrophages by chloroquine used alone and in combination with ciprofloxacin or azithromycin. J Inflamm Res. 2015;8:29–47.PubMed PubMed Central CAS Google Scholar 

55.Keshavarzi F. Fungistatic effect of hydroxychloroquine, lessons from a case. Med Mycol Case Rep. 2016;13:17–8.PubMed PubMed Central Article Google Scholar 

56.Levitz SM, Harrison TS, Tabuni A, Liu X. Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation. J Clin Invest. 1997;100:1640–6.PubMed PubMed Central Article CAS Google Scholar 

57.Weber SM, Levitz SM, Harrison TS. Chloroquine and the fungal phagosome. Curr Opin Microbiol. 2000;3:349–53.PubMed Article CAS Google Scholar 

58.Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017;16:411–9.PubMed Article CAS Google Scholar 

59.Belizna C. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome. Autoimmun Rev. 2015;14:358–62.PubMed Article CAS Google Scholar 

60.Broder A, Putterman C. Hydroxychloroquine use is associated with lower odds of persistently positive antiphospholipid antibodies and/or lupus anticoagulant in systemic lupus erythematosus. J Rheumatol. 2013;40:30–3.PubMed Article CAS Google Scholar 

61.Burgos PI, Alarcón GS. Thrombosis in systemic lupus erythematosus: risk and protection. Expert Rev Cardiovasc Ther. 2009;7:1541–9.PubMed Article Google Scholar 

62.Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients. Curr Rheumatol Rep. 2011;13:77–80.PubMed Article CAS Google Scholar 

63.Szymezak J, Ankri A, Fischer A-M, Darnige L. Hydroxychloroquine: a new therapeutic approach to the thrombotic manifestations of antiphospholipid syndrome. Rev Med Intern. 2010;31:854–7.Article CAS Google Scholar 

64.Rand JH, Wu XX, Quinn AS, Ashton AW, Chen PP, Hathcock JJ, et al. Hydroxychloroquine protects the annexinA5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood. 2010;115:2292–9.PubMed PubMed Central Article CAS Google Scholar 

65.Cummins D, Faint R, Yardumian DA, Dawling S, Mackie I, Machin SJ. The in vitro and ex vivo effects of chloroquine sulphate on platelet function: implications for malaria prophylaxis in patients with impaired haemostasis. J Trop Med Hyg. 1990;93:112–5.PubMed CAS Google Scholar 

66.Jancinová V, Nosál R, Petríková M. On the inhibitory effect of chloroquine on blood platelet aggregation. Thromb Res. 1994;74:495–504.PubMed Article Google Scholar 

67.Cansu DU, Korkmaz C. Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA. Rheumatology (Oxford). 2008;47:378–9.Article CAS Google Scholar 

68.Shojania K, Koehler BE, Elliott T. Hypoglycemia induced by hydroxychloroquine in a type II diabetic treated for polyarthritis. J Rheumatol. 1999;26:195–6.PubMed CAS Google Scholar 

69.Unübol M, Ayhan M, Guney E. Hypoglycemia induced by hydroxychloroquine in a patient treated for rheumatoid arthritis. J Clin Rheumatol. 2011;17:46–7.PubMed Article Google Scholar 

70.Quatraro A, Consoli G, Magno M, Caretta F, Nardozza A, Ceriello A, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med. 1990;112:678–81.PubMed Article CAS Google Scholar 

71.Pareek A, Chandurkar N, Thomas N, Viswanathan V, Deshpande A, Gupta OP, et al. Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone. Curr Med Res Opin. 2014;30:1257–66.PubMed Article CAS Google Scholar 

72.Cairoli E, Rebella M, Danese N, Garra V, Borba EF. Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect. Lupus. 2012;21:1178–82.PubMed Article CAS Google Scholar 

73.Hage MP, Al-Badri MR, Azar ST. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocrinol Metab. 2014;5:77–85.PubMed PubMed Central Article CAS Google Scholar 

74.Wallace DJ, Metzger AL, Stecher VJ, Turnbull BA, Kern PA. Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids. Am J Med. 1990;89:322–6.PubMed Article CAS Google Scholar 

75.Wilhelm AJ, Major AS. Accelerated atherosclerosis in SLE: mechanisms and prevention approaches. Int J Clin Rheumtol. 2012;7:527–39.PubMed PubMed Central Article CAS Google Scholar 

76.Geser A, Brubaker G, Draper CC. Effect of a malaria suppression program on the incidence of African Burkitt’s lymphoma. Am J Epidemiol. 1989;129:740–52.PubMed Article CAS Google Scholar 

77.Marmor MF, Kellner U, Lai TYY, Lyons JS, Mieler WF. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118:415–22.PubMed Article Google Scholar 

78.Van Beek MJ, Piette WW. Antimalarials. Dermatol Clin. 2001;19:147–60.PubMed Article Google Scholar 

79.Khraishi MM, Singh G. The role of anti-malarials in rheumatoid arthritis–the American experience. Lupus. 1996;5(Suppl 1):S41–4.PubMed CAS Google Scholar 

80.Kalia S, Dutz JP. New concepts in antimalarial use and mode of action in dermatology. Dermatol Ther. 2007;20:160–74.PubMed Article Google Scholar 

81.Tehrani R, Ostrowski RA, Hariman R, Jay WM. Ocular toxicity of hydroxychloroquine. Semin Ophthalmol. 2008;23:201–9.PubMed Article Google Scholar 

82.Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132:1453–60.PubMed Article Google Scholar 

83.Michaelides M, Stover NB, Francis PJ, Weleber RG. Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol. 2011;129:30–9.PubMed Article CAS Google Scholar 

84.Marmor MF, Melles RB. Disparity between visual fields and optical coherence tomography in hydroxychloroquine retinopathy. Ophthalmology. 2014;121:1257–62.PubMed Article Google Scholar 

85.Easterbrook M. Ocular effects and safety of antimalarial agents. Am J Med. 1988;85:23–9.PubMed Article CAS Google Scholar 

86.Lozier JR, Friedlaender MH. Complications of antimalarial therapy. Int Ophthalmol Clin. 1989;29:172–8.PubMed Article CAS Google Scholar 

87.Tonnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy—a review of the literature. Immunopharmacol Immunotoxicol. 2013;35:434–42.PubMed Article CAS Google Scholar 

88.Yogasundaram H, Putko BN, Tien J, Paterson DI, Cujec B, Ringrose J, et al. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment. Can J Cardiol. 2014;30:1706–15.PubMed Article Google Scholar 

89.Soong TR, Barouch LA, Champion HC, Wigley FM, Halushka MK. New clinical and ultrastructural findings in hydroxychloroquine-induced cardiomyopathy–a report of 2 cases. Hum Pathol. 2007;38:1858–63.PubMed Article Google Scholar 

90.Naqvi TZ, Luthringer D, Marchevsky A, Saouf R, Gul K, Buchbinder NA. Chloroquine-induced cardiomyopathy-echocardiographic features. J Am Soc Echocardiogr. 2005;18:383–7.PubMed Article Google Scholar 

91.Keating RJ, Bhatia S, Amin S, Williams A, Sinak LJ, Edwards WD. Hydroxychloroquine-induced cardiotoxicity in a 39-year-old woman with systemic lupus erythematosus and systolic dysfunction. J Am Soc Echocardiogr. 2005;18:981.PubMed Article Google Scholar 

92.Costedoat-Chalumeau N, Hulot JS, Amoura Z, Delcourt A, Maisonobe T, Dorent R, et al. Cardiomyopathy related to antimalarial therapy with illustrative case report. Cardiology. 2007;107:73–80.PubMed Article Google Scholar 

93.Cotroneo J, Sleik KM, Rene Rodriguez E, Klein AL. Hydroxychloroquine-induced restrictive cardiomyopathy. Eur J Echocardiogr. 2007;8:247–51.PubMed Article Google Scholar 

94.Cervera A, Espinosa G, Font J, Ingelmo M. Cardiac toxicity secondary to long term treatment with chloroquine. Ann Rheum Dis. 2001;60:301.PubMed PubMed Central Article CAS Google Scholar 

95.Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol. 2000;27:2927–31.PubMed CAS Google Scholar 

96.Kwon J-B, Kleiner A, Ishida K, Godown J, Ciafaloni E, Looney RJ. Hydroxychloroquine-induced myopathy. J Clin Rheumatol. 2010;16:28–31.PubMed Article Google Scholar 

97.Estes ML, Ewing-Wilson D, Chou SM, Mitsumoto H, Hanson M, Shirey E, et al. Chloroquine neuromyotoxicity. Clinical and pathologic perspective. Am J Med. 1987;82:447–55.PubMed Article CAS Google Scholar 

98.Al-Bari M, Alim A. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017;5:1–13.Article CAS Google Scholar 

99.Naarding MA, Baan E, Pollakis G, Paxton WA. Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4 + T-lymphocytes. Retrovirology. 2007;4:6.PubMed PubMed Central Article CAS Google Scholar 

100.Jiang MC, Lin JK, Chen SS. Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine. Biochem Biophys Res Commun. 1996;4(226):1–7.Article Google Scholar 

101.Benveniste O, Flahault A, Rollot F, Elbim C, Estaquier J, Pedron B, et al. Mechanisms involved in the low-level regeneration of CD4 + cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J Infect Dis. 2005;191:1670–9.PubMed Article Google Scholar 

102.Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12:1365–71.PubMed Article CAS Google Scholar 

103.Funderburg N, Luciano AA, Jiang W, Rodriguez B, Sieg SF, Lederman MM. Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis. PLoS One. 2008;3:1–7.Article CAS Google Scholar 

104.French MA, King MS, Tschampa JM, da Silva BA, Landay AL. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4 + T cells. J Infect Dis. 2009;200:1212–5.PubMed Article CAS Google Scholar 

105.Piconi S, Parisotto S, Rizzardini G, Passerini S, Terzi R, Argenteri B, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. Blood. 2011;118:3263–72.PubMed Article CAS Google Scholar 

106.van Loosdregt J, Spreafico R, Rossetti M, Prakken BJ, Lotz M, Albani S. Hydroxychloroquine preferentially induces apoptosis of CD45RO + effector T cells by inhibiting autophagy: a possible mechanism for therapeutic modulation of T cells. J Allergy Clin Immunol. 2013;131(1443–1446):e1.Google Scholar 

107.Chomont N, DaFonseca S, Vandergeeten C, Ancuta P, Sékaly R-P. Maintenance of CD4 + T-cell memory and HIV persistence: keeping memory, keeping HIV. Curr Opin HIV AIDS. 2011;6:30–6.PubMed Article Google Scholar 

108.Chiang G, Sassaroli M, Louie M, Chen H, Stecher VJ, Sperber K. Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther. 1996;18:1080–92.PubMed Article CAS Google Scholar 

109.Savarino A, Gennero L, Sperber K, Boelaert JR. The anti-HIV-1 activity of chloroquine. J Clin Virol. 2001;20:131–5.PubMed Article CAS Google Scholar 

110.Savarino A, Lucia MB, Rastrelli E, Rutella S, Golotta C, Morra E, et al. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr. 2004;35:223–32.PubMed Article CAS Google Scholar 

111.Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015;12:51.PubMed PubMed Central Article CAS Google Scholar 

112.Sperber K, Louie M, Kraus T, Proner J, Sapira E, Lin S, et al. Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1. Clin Ther. 1995;17:622–36.PubMed Article CAS Google Scholar 

113.Ross W. Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1. Clin Ther. 1997;19:913–23.PubMed Article Google Scholar 

114.Paton NI, Goodall RL, Dunn DT, Franzen S, Collaco-Moraes Y, Gazzard BG, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012;308:353–61.PubMed Article CAS Google Scholar 

115.Routy JP, Angel JB, Patel M, Kanagaratham C, Radzioch D, Kema I, et al. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med. 2015;16:48–56.PubMed Article CAS Google Scholar 

116.Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007;30:297–308.PubMed Article CAS Google Scholar 

117.Million M, Raoult D. Recent advances in the study of Q fever epidemiology, diagnosis and management. J Infect. 2015;71:S2–9.PubMed Article Google Scholar 

118.Maurin M, Raoult D. Q fever. Clin Microbiol Rev. 1999;12:518–53.PubMed PubMed Central CAS Article Google Scholar 

119.Botelho-Nevers E, Fournier P-E, Richet H, Fenollar F, Lepidi H, Foucault C, et al. Coxiella burnetii infection of aortic aneurysms or vascular grafts: report of 30 new cases and evaluation of outcome. Eur J Clin Microbiol Infect Dis. 2007;26:635–40.PubMed Article CAS Google Scholar 

120.Levy PY, Drancourt M, Etienne J, Auvergnat JC, Beytout J, Sainty JM, et al. Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother. 1991;35:533–7.PubMed PubMed Central Article CAS Google Scholar 

121.Lam C, Mathison GE. Effect of low intraphagolysosomal pH on antimicrobial activity of antibiotics against ingested staphylococci. J Med Microbiol. 1983;16:309–16.PubMed Article CAS Google Scholar 

122.Raoult D, Drancourt M, Vestris G. Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. Antimicrob Agents Chemother. 1990;34:1512–4.PubMed PubMed Central Article CAS Google Scholar 

123.Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999;159:167–73.PubMed Article CAS Google Scholar 

124.Lagier J-C, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult D. Treatment of classic Whipple’s disease: from in vitro results to clinical outcome. J Antimicrob Chemother. 2014;69:219–27.PubMed Article CAS Google Scholar 

125.Fenollar F, Lagier J-C, Raoult D. Tropheryma whipplei and Whipple’s disease. J Infect. 2014;69:103–12.PubMed Article Google Scholar 

126.Fenollar F, Puéchal X, Raoult D. Whipple’s disease. N Engl J Med. 2007;356:55–66.PubMed Article CAS Google Scholar 

127.Keinath RD, Merrell DE, Vlietstra R, Dobbins WO. Antibiotic treatment and relapse in Whipple’s disease. Long-term follow-up of 88 patients. Gastroenterology. 1985;88:1867–73.PubMed Article CAS Google Scholar 

128.El-Abassi R, Soliman MY, Williams F, England JD. Whipple’s disease. J Neurol Sci. 2017;377:197–206.PubMed Article Google Scholar 

129.Garas G, Cheng WS, Abrugiato R, Forbes GM. Clinical relapse in Whipple’s disease despite maintenance therapy. J Gastroenterol Hepatol. 2000;15:1223–6.PubMed Article CAS Google Scholar 

130.Price RN, von Seidlein L, Valecha N, Nosten F, Baird JK, White NJ. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14:982–91.PubMed PubMed Central Article Google Scholar 

131.Hoppe HC, van Schalkwyk DA, Wiehart UIM, Meredith SA, Egan J, Weber BW. Antimalarial quinolines and artemisinin inhibit endocytosis in Plasmodium falciparum. Antimicrob Agents Chemother. 2004;48:2370–8.PubMed PubMed Central Article CAS Google Scholar 

132.Byrd TF, Horwitz MA. Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. J Clin Invest. 1991;88:351–7.PubMed PubMed Central Article CAS Google Scholar 

133.Henriet SS, Jans J, Simonetti E, Kwon-Chung KJ, Rijs AJ, Hermans PW, et al. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease. J Infect Dis. 2013;207:1932–9.PubMed Article CAS Google Scholar 

134.Boelaert JR, Appelberg R, Gomes MS, Blasi E, Mazzolla R, Grosset J, et al. Experimental results on chloroquine and AIDS-related opportunistic infections. J Acquir Immune Defic Syndr. 2001;26:300–1.PubMed Article CAS Google Scholar 

135.Dias-Melicio LA, Moreira AP, Calvi SA, Soares AM. Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron. Microbiol Immunol. 2006;50:307–14.PubMed Article CAS Google Scholar 

136.Castro LA, Fox SJ, Chen X, Liu K, Bellan SE, Dimitrov NB, et al. Assessing real-time Zika risk in the United States. BMC Infect Dis. 2017;17:284.PubMed PubMed Central Article Google Scholar 

137.Cragan JD, Mai CT, Petersen EE, Liberman RF, Forestieri NE, Stevens AC, et al. Baseline prevalence of birth defects associated with congenital Zika virus infection—Massachusetts, North Carolina, and Atlanta, Georgia, 2013–2014. MMWR Morb Mortal Wkly Rep. 2017;66:219–22.PubMed PubMed Central Article Google Scholar 

138.Shiryaev SA, Mesci P, Pinto A, Fernandes I, Sheets N, Shresta S, et al. Repurposing of the anti-malaria drug chloroquine for Zika virus treatment and prophylaxis. Sci Rep. 2017;7(1):15771.PubMed PubMed Central Article CAS Google Scholar 

139.Burt FJ, Chen W, Miner JJ, Lenschow DJ, Merits A, Schnettler E, et al. Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen. Lancet Infect Dis. 2017;17:e107–17.PubMed Article CAS Google Scholar 

140.Simon F, Javelle E, Oliver M, Leparc-Goffart I, Marimoutou C. Chikungunya virus infection. Curr Infect Dis Rep. 2011;13:218–28.PubMed PubMed Central Article Google Scholar 

141.Martõâ-Carvajal A, Ramon-Pardo P, Javelle E, Simon F, Aldighieri S, Horvath H, et al. Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: a systematic review. PLoS One. 2017;12(6):e0179028.Article CAS Google Scholar 

142.Ravindran V, Alias G. Efficacy of combination DMARD therapy vs. hydroxychloroquine monotherapy in chronic persistent chikungunya arthritis: a 24-week randomized controlled open label study. Clin Rheumatol. 2017;36:1335–40.PubMed Article Google Scholar 

143.Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF, Al-Bari MAA. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23:231–69.PubMed Article CAS Google Scholar 

144.Jessop S, Whitelaw D, Jordaan F. Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2001;1:CD002954.Google Scholar 

145.Jessop S, Whitelaw DA, Delamere FM. Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2009;4:CD002954. Google Scholar 

146.Jessop S, Whitelaw DA, Grainge MJ, Jayasekera P. Drugs for discoid lupus erythematosus. Cochrane Database Syst Rev. 2017;5:CD002954. Article Google Scholar 

147.Mok CC, Mak A, Ma KM. Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus. Lupus. 2005;14:106–12.PubMed Article CAS Google Scholar 

148.Lakshminarayanan S, Walsh S, Mohanraj M, Rothfield N. Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. J Rheumatol. 2001;28:102–8.PubMed CAS Google Scholar 

149.O’Dell JR, Haire C, Erikson N, Drymalski W, Palmer W, Maloley P, et al. Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrexate. J Rheumatol Suppl. 1996;44:72–4.PubMed Google Scholar 

150.O’Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369:307–18.PubMed Article CAS Google Scholar 

151.Combe B, Guttierrez M, Anaya JM, Sany J. Possible efficacy of hydroxychloroquine on accelerated nodulosis during methotrexate therapy for rheumatoid arthritis. J Rheumatol. 1993;20:755–6.PubMed CAS Google Scholar 

152.Thorne I, Sutcliffe N. Sjögren’s syndrome. Br J Hosp Med. 2017;78:438–42.Article Google Scholar 

153.Wang S, Zhang L, Wei P, Hua H. Is hydroxychloroquine effective in treating primary Sjogren’s syndrome: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2017;18:186. PubMed Central Article CAS Google Scholar 

154.Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, et al. Primary Sjogren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford). 2014;53:839–44.Article Google Scholar 

155.Oxholm P, Prause JU, Schiødt M. Rational drug therapy recommendations for the treatment of patients with Sjögren’s syndrome. Drugs. 1998;56:345–53.PubMed Article CAS Google Scholar 

156.Clinical Practice Guidelines. Accessed 14 Apr 2018.

157.Poh-Fitzpatrick M. Porphyria cutanea tarda: treatment options revisited. Clin Gastroenterol Hepatol. 2012;10:1410–1.PubMed Article Google Scholar 

158.Solomon L. Chronic ulcerative stomatitis. Oral Dis. 2008;14:383–9.PubMed Article CAS Google Scholar 

159.Ochsendorf FR. Use of antimalarials in dermatology. J Dtsch Dermatol Ges. 2010;8:829–44. Article Google Scholar 

160.Tutrone WD, Spann CT, Scheinfeld N, Deleo VA. Polymorphic light eruption. Dermatol Ther. 2003;16:28–39.PubMed Article Google Scholar 

161.Pareek A, Khopkar U, Sacchidanand S, Chandurkar N, Naik GS. Comparative study of efficacy and safety of hydroxychloroquine and chloroquine in polymorphic light eruption: a randomized, double-blind, multicentric study. Indian J Dermatol Venereol Leprol. 2008;74:18–22.PubMed Article Google Scholar 

162.Bedoya V. Effect of chloroquine on malignant lymphoreticular and pigmented cells in vitro. Cancer Res. 1970;30:1262–75.PubMed CAS Google Scholar 

163.Pascolo S. Time to use a dose of chloroquine as an adjuvant to anti-cancer chemotherapies. Eur J Pharmacol. 2016;771:139–44.PubMed Article CAS Google Scholar 

164.Verbaanderd C, Maes H, Schaaf MB, Sukhatme VP, Pantziarka P, Sukhatme V, et al. Repurposing drugs in oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience. 2017;11:1–35.Article Google Scholar 

165.Shi TT, Yu XX, Yan LJ, Xiao HT. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother Pharmacol. 2017;79:287–94.PubMed Article CAS Google Scholar 

166.Manic G, Obrist F, Kroemer G, Vitale I, Galluzzi L. Chloroquine and hydroxychloroquine for cancer therapy. Mol Cell Oncol. 2014;1:e29911.PubMed PubMed Central Article Google Scholar 

167.Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017;17:528–42.PubMed Article CAS Google Scholar 

168.Jiang P, Zhao Y, Shi W, Deng X, Xie G, Mao Y, et al. Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by chloroquine in human breast cancer cell line Bcap-37. Cell Physiol Biochem. 2008;22:431–40.PubMed Article CAS Google Scholar 

169.Jiang P-D, Zhao Y-L, Deng X-Q, Mao Y-Q, Shi W, Tang Q-Q, et al. Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother. 2010;64:609–14.PubMed Article CAS Google Scholar 

170.Boya P, Gonzalez-Polo R-A, Poncet D, Andreau K, Vieira HLA, Roumier T, et al. Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003;22:3927–36.PubMed Article CAS Google Scholar 

171.Zheng Y, Zhao Y-L, Deng X, Yang S, Mao Y, Li Z, et al. Chloroquine inhibits colon cancer cell growth in vitro and tumor growth in vivo via induction of apoptosis. Cancer Invest. 2009;27:286–92.PubMed Article CAS Google Scholar 

172.Sternglanz H, Yielding KL, Pruitt KM. Nuclear magnetic resonance studies of the interaction of chloroquine diphosphate with adenosine 5′-phosphate and other nucleotides. Mol Pharmacol. 1969;5:376–81.PubMed CAS Google Scholar 

173.Krajewski WA. Alterations in the internucleosomal DNA helical twist in chromatin of human erythroleukemia cells in vivo influences the chromatin higher-order folding. FEBS Lett. 1995;361:149–52.PubMed Article CAS Google Scholar 

174.Ratikan JA, Sayre JW, Schaue D. Chloroquine engages the immune system to eradicate irradiated breast tumors in mice. Int J Radiat Oncol Biol Phys. 2013;87:761–8.PubMed Article CAS Google Scholar 

175.Patel AV, Stickler DE, Tyor WR. Neurosarcoidosis. Curr Treat Options Neurol. 2007;9:161–8.PubMed Article Google Scholar 

176.Sharma OP. Effectiveness of chloroquine and hydroxychloroquine in treating selected patients with sarcoidosis with neurological involvement. Arch Neurol. 1998;55:1248–54.PubMed Article CAS Google Scholar 

177.Pittock SJ, Debruyne J, Krecke KN, Giannini C, van den Ameele J, De Herdt V, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 2010;133:2626–34.PubMed Article Google Scholar 

178.Tan BL, Agzarian M, Schultz DW. CLIPPERS: induction and maintenance of remission using hydroxychloroquine. Neurol Neuroimmunol Neuroinflammation. 2015;2:e56–7.Article Google Scholar 

179.Shadfar S, Hwang CJ, Lim M-S, Choi D-Y, Hong JT. Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents. Arch Pharm Res. 2015;38:2106–19.PubMed Article CAS Google Scholar 

180.Van Gool WA, Weinstein HC, Scheltens PK, Walstra GJ. Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet. 2001;358:455–60.PubMed Article Google Scholar 

181.Koch MW, Zabad R, Giuliani F, Hader W, Lewkonia R, Metz L, et al. Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis. J Neurol Sci. 2015;358:131–7.PubMed Article CAS Google Scholar 

182.Mandoj C, Renna R, Plantone D, Sperduti I, Cigliana G, Conti L, et al. Anti-annexin antibodies, cholesterol levels and disability in multiple sclerosis. Neurosci Lett. 2015;606:156–60.PubMed Article CAS Google Scholar


Due to significantly improved outcome, Henry Ford Health System continues hydroxychloroquine study

Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France

FDA Hydroxychloroquine Ban, Fake Science, And Political Agendas

Share on facebook
Share on twitter
Share on whatsapp
On Trend

Latest Stories

Dr. Harvey Risch: Hydroxychloroquine, Ivermectin, and Other Therapeutics Highly Effective in Early COVID Treatment

I’ve railed against this in the media that we are a part of, and the way that the propaganda reacts to this is, “Ignore it. Ignore all of this.” I’m saying this now because the general public has to be the one that gets angry. The general public should be furious at the way people have been treated in the country by suppression of these drugs, by that kind of website that suppresses the ability of doctors to practice medicine.

Read More »

A Judge Stands up to a Hospital: “Step Aside” and Give a Dying Man Ivermectin

The judge’s finest moment may have been when he dashed the most glaring myth about ivermectin—that it is not safe, despite decades of use that shows otherwise. Noting that all drugs have side effects, Judge Fullerton listed ivermectin’s effects from a government website.
“(N)umber one, generally well tolerated; number two, dizziness; number three, pruritus; number four, nausea/diarrhea. These are the side effects for the dosage that’s being asked to be administered,” he said. “The risks of these side effects are so minimal that Mr. Ng’s current situation outweighs that risk by one-hundredfold.”

Read More »