Antiviral hyperactivation-limiting therapeutics as a novel class for the treatment of HIV/AIDS: Focus on VS411

Expert Opinion on Investigational Drugs

Volumn 20, Issue 4, 2011, Pages 559-565

  Uglietti, Alessia ^a   Maserati, Renato ^a  

^a FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

Author keywords

antiretroviral therapy; AV HALTs; HIV 1; immunomodulating drug; VS411

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DIDANOSINE; DIDANOSINE PLUS HYDROXYUREA; HYDROXYUREA; UNCLASSIFIED DRUG; VIRUS RNA; VS 411;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; CD4+ T LYMPHOCYTE; COMBINATION CHEMOTHERAPY; CONTROLLED RELEASE FORMULATION; CYTOPENIA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LYMPHOCYTE PROLIFERATION; NONHUMAN; PANCREATITIS; PATIENT COMPLIANCE; PERIPHERAL NEUROPATHY; REVIEW; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; VIRUS ACTIVATION; VIRUS LOAD; VIRUS REPLICATION;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTI-HIV AGENTS; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CLINICAL TRIALS AS TOPIC; DIDANOSINE; DRUG COMBINATIONS; DRUG EVALUATION, PRECLINICAL; HIV INFECTIONS; HUMANS; HYDROXYUREA; LYMPHOCYTE ACTIVATION; UREA; VIRAL LOAD;

EID: 79952647280     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2011.565047     Document Type: Review

References (52)

1. Sterne JA, Hernan MA, Ledergerber B, et al. Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study. Lancet 2005;366:378-84 (Pubitemid 41073955)
2. Lubinski C, Aberg J, Bardeguez AD, et al. HIV policy: the path forward - a joint position paper of the HIV Medicine Association of the Infectious Diseases Society of America and the American College of Physicians. Clin Infect Dis 2009;20:1335-44
3. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 2003;163:2187-95 (Pubitemid 37248783)
4. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis 2003;187:1534-43 (Pubitemid 36578959)
5. Douek DC. Disrupting T-cell homeostasis: how HIV-1 infection causes disease. AIDS Rev 2003;5:172-7 (Pubitemid 37336634)
6. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006;12:1365-71 (Pubitemid 44924494)
7. Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997;277:112-16 (Pubitemid 27450659)
8. Foli A, Maiocchi MA, Lisziewicz J, Lori F. A checkpoint in the cell cycle progression as a therapeutic target to inhibit HIV replication. J Infect Dis 2007;196:1409-15 (Pubitemid 351412015)
9. Ameisen JC, Capron A. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today 1991;12:102-5
10. Meyaard L, Otto SA, Jonker RR, et al. Programmed death of T cells in HIV-1 infection. Science 1992;257:217-19
11. Finkel TH, Tudor-Williams G, Banda NK, et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med 1995;1:129-34
12. Grossman Z, Paul WE. The impact of HIV on naíve T-cell homeostasis. Nat Med 2000;6:976-7
13. McCune JM. The dynamics of CD4+ T-cell depletion in HIV disease. Nature 2001;410:974-9 (Pubitemid 32335848)
14. Hellerstein MK, Hoh RA, Hanley MB, et al. Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection. J Clin Invest 2003;112:956-66 (Pubitemid 38063753)
15. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009;338:a3172
16. De Forni D, Stevens MR, Lori F. Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDS. Br J Pharmacol 2010;161:830-43
17. Murray SM, Down CM, Boulware DR, et al. Reduction of immune activation with chloroquine therapy during chronic HIV infection. J Virol 2010;84:12082-6
18. Read SW, DeGrezia M, Ciccone EJ, et al. The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants. PloS One 2010;5:e11937
19. Montoya CJ, Jaimes F, Higuita EA, et al. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial. Trials 2009;10:41
20. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995;332:1317-22
21. Navarra P, Preziosi P. Hydroxyurea: new insights on an old drug. Crit Rev Oncol Hematol 1999;29:249-55 (Pubitemid 29158970)
22. Smith CH. Use of hydroxyurea in psoriasis. Clin Exp Dermatol 1999;24:2-6
23. Davies SC, Gilmore A. The role of hydroxyurea in the management of sickle cell disease. Blood Rev 2003;17:99-109 (Pubitemid 36372974)
24. Lori F, Malykh A, Cara A, et al. Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. Science 1994;266:801-5 (Pubitemid 24359288)
25. Lori F, Gallo RC, Malykh A, et al. Didanosine but not high doses of hydroxyurea rescue pigtail macaque from a lethal dose of SIV(smmpbj14). AIDS Res Hum Retroviruses 1997;13:1083-8 (Pubitemid 27355737)
26. Johns DG, Gao WY. Selective depletion of DNA precursors: an evolving strategy for potentiation of dideoxynucleoside activity against human immunodeficiency virus. Biochem Pharmacol 1998;55:1551-6 (Pubitemid 28223446)
27. Yarbro JW. Mechanism of action of hydroxyurea. Semin Oncol 1992;19:1-10
28. Malley SD, Grange JM, Hamedi-Sangsari F, Vila JR. Synergistic anti-human immunodeficiency virus type 1 effect of hydroxamate compounds with 2′,3′-dideoxyinosine in infected resting human lymphocytes. Proc Natl Acad Sci USA 1994;91:11017-21
29. Gao WY, Johns DG, Chokekuchai S, Mitsuya H. Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2′,3′- dideoxynucleoside activities against replication of human immunodeficiency virus. Proc Natl Acad Sci USA 1995;92:8333-7
30. De Boer RJ, Boucher CA, Perelson AS. Target cell availability and the successful suppression of HIV by hydroxyurea and didanosine. AIDS 1998;12:1567-70 (Pubitemid 28418325)
31. Ravot E, Lisziewicz J, Lori F. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Drugs 1999;58:953-63 (Pubitemid 30055040)
32. Lisziewicz J, Foli A, Wainberg M, Lori F. Hydroxyurea in the treatment of HIV infection: clinical efficacy and safety concerns. Drug Saf 2003;26:605-24 (Pubitemid 36871835)
33. Kelly LM, Lisziewicz J, Lori F. "Virostatics" as a potential new class of HIV drugs. Curr Pharm Des 2004;10:4103-20
34. Heredia A, Davis C, Amoroso A, et al. Induction of G1 cycle arrest in T lymphocytes results in increased extracellular levels of beta-chemokines: a strategy to inhibit R5 HIV-1. Proc Natl Acad Sci USA 2003;100:4179-84 (Pubitemid 36418177)
35. Biron F, Lucht F, Peyramond D, et al. Pilot clinical trial of the combination of hydroxyurea and didanosine in HIV-1 infected individuals. Antiviral Res 1996;29:111-13 (Pubitemid 26094529)
36. Foli A, Lori F, Maserati R, et al. Hydroxyurea and didanosine is a more potent combination than hydroxyurea and zidovudine. Antivir Ther 1997;2:31-8 (Pubitemid 27232592)
37. Vila J, Nugier F, Bargues G, et al. Absence of viral rebound after treatment of HIV-infected patients with didanosine and hydroxycarbamide. Lancet 1997;350:635-6 (Pubitemid 27367799)
38. Montaner JS, Zala C, Conway B, et al. A pilot study of hydroxyurea among patients with advanced human immunodeficiency virus (HIV) disease receiving chronic didanosine therapy: Canadian HIV trials network protocol 080. J Infect Dis 1997;175:801-6 (Pubitemid 27142951)
39. Lori F, Malykh AG, Foli A, et al. Combination of a drug targeting the cell with a drug targeting the virus controls human immunodeficiency virus type 1 resistance. AIDS Res Hum Retroviruses 1997;13:1403-9 (Pubitemid 27460837)
40. Rutschmann OT, Opravil M, Iten A, et al. A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study. AIDS 1998;12:F71-7
41. Frank I, Bosch RJ, Fiscus S, et al. Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307. AIDS Res Hum Retroviruses 2004;20:916-26 (Pubitemid 39369697)
42. Lori F, Pollard RB, Whitman L, et al. Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency. AIDS Res Hum Retroviruses 2005;21:263-72 (Pubitemid 40632358)
43. Lori F, Foli A, Groff A, et al. Optimal suppression of HIV replication by low-dose hydroxyurea through the combination of antiviral and cytostatic ('virostatic') mechanisms. AIDS 2005;19:1173-81 (Pubitemid 41059258)
44. Gao WY, Johns DG, Mitsuya H. Anti-human immunodeficiency virus type 1 activity of hydroxyurea in combination with 2′,3′- dideoxynucleosides. Mol Pharmacol 1994;46:767-72 (Pubitemid 24334770)
45. Foli A, Benvenuto F, Piccinini G, et al. Direct analysis of mitochondrial toxicity of antiretroviral drugs. AIDS 2001;15:1687-94 (Pubitemid 32918123)
46. Katabira E, Cahn P, Lange J, et al. Both Immune Activation and Viral Load are Reduced Within 28 Days by VS411, the First AntiViral-HyperActivation Limiting Therapeutic (AV-HALT). A Phase II Study. Poster THPE0066 presented at XVIII International AIDS Conference; 18 - 23 July 2010; Vienna, Austria
47. Donehower RC. An overview of the clinical experience with hydroxyurea. Semin Oncol 1992;19:11-19
48. Palmer S, Shafer RW, Merigan TC. Hydroxyurea enhances the activities of didanosine, 9-[2-(phosphonylmethoxy) ethyl]adenine, and 9-[2- (phosphonylmethoxy)propyl]adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates. Antimicrol Agents Chemother 1999;43:2046-50 (Pubitemid 29395207)
49. Lori F, Foli A, Maserati R, et al. Control of HIV during a structured treatment interruption in chronically infected individuals with vigorous T cell responses. HIV Clin Trials 2002;3:115-24 (Pubitemid 34520988)
50. Lori F. Virostatics: a new frontier in the treatment of HIV/AIDS. J Acquir Immune Defic Syndr 2006;42:S1-3
51. Miller S. Hydroxyurea: eight years' experience. J Acquir Immune Defic Syndr 2006;42:S16-17
52. Hunt PW, Brenchley, Sinclair E, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis 2008;197:126-33 (Pubitemid 351263476)