AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus (HIV) infection. Unlike other antiretroviral agents given to reduce viral replication, AV-HALTs are single or combination drugs designed to reduce the rate of viral replication while, at the same time, also directly reducing the state of immune system hyperactivation now believed to drive the loss of CD4+ T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome (AIDS).
Chronic immune stimulation due to persistent HIV replication and microbial translocation across impaired gut-associated lymphoid tissues (GALT) induces continuous T-cell activation and proliferation of both HIV-infected and bystander cells, ultimately resulting in the exhaustion of the immune system.[1][2][3][4][5][6]
There is a growing recognition that successful long-term therapy for the treatment of HIV infection should not only reduce viral replication, but also limit the hyper-activation of the immune system now proposed as the cause of the eventual progression to AIDS.[7][8][9][10] AV-HALTs are designed to accomplish two goals – the reduction of viral load (decreased viral load) and the reduction of immune system hyperactivation (decreased markers of cellular activation and proliferation). First generation AV-HALTs accomplish this by combining an antiviral drug (e.g. didanosine) with a cytostatic agent (e.g. hydroxyurea).[11]
VS1-002, investigational second generation single-drug AV-HALT (Pre-clinical) - ViroStatics, srl[12]
Synonymsedit
virostatics (antiVIRal + cytOSTATICS)
Referencesedit
^Ameisen, J. C.; Capron, A (1991). "Cell dysfunction and depletion in AIDS: The programmed cell death hypothesis". Immunology Today. 12 (4): 102–5. doi:10.1016/0167-5699(91)90092-8. PMID 1676268.
^McCune, J. M. (2001). "The dynamics of CD4+ T-cell depletion in HIV disease". Nature. 410 (6831): 974–9. Bibcode:2001Natur.410..974M. doi:10.1038/35073648. PMID 11309627. S2CID 4419786.
^Meyaard, L.; Otto, S. A.; Keet, I. P.; Roos, M. T.; Miedema, F. (1994). "Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease". Journal of Clinical Investigation. 93 (3): 982–988. doi:10.1172/JCI117105. PMC294014. PMID 8132784.
^Grossman, Z; Paul, W. E. (2000). "The impact of HIV on naïve T-cell homeostasis". Nature Medicine. 6 (9): 976–7. doi:10.1038/79667. PMID 10973313. S2CID 21350300.
^Hellerstein, M. K.; Hoh, R. A.; Hanley, M. B.; Cesar, D; Lee, D; Neese, R. A.; McCune, J. M. (2003). "Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection". Journal of Clinical Investigation. 112 (6): 956–66. doi:10.1172/JCI17533. PMC193663. PMID 12975480.
^Finkel, T. H.; Tudor-Williams, G; Banda, N. K.; Cotton, M. F.; Curiel, T; Monks, C; Baba, T. W.; Ruprecht, R. M.; Kupfer, A (1995). "Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes". Nature Medicine. 1 (2): 129–34. doi:10.1038/nm0295-129. PMID 7585008. S2CID 37444589.
^Brenchley, J. M.; Price, D. A.; Schacker, T. W.; Asher, T. E.; Silvestri, G; Rao, S; Kazzaz, Z; Bornstein, E; Lambotte, O; Altmann, D; Blazar, B. R.; Rodriguez, B; Teixeira-Johnson, L; Landay, A; Martin, J. N.; Hecht, F. M.; Picker, L. J.; Lederman, M. M.; Deeks, S. G.; Douek, D. C. (2006). "Microbial translocation is a cause of systemic immune activation in chronic HIV infection". Nature Medicine. 12 (12): 1365–71. doi:10.1038/nm1511. PMC1717013. PMID 17115046.
^Douek, D. C. (2003). "Disrupting T-cell homeostasis: How HIV-1 infection causes disease". AIDS Reviews. 5 (3): 172–7. PMID 14598566.
^Hunt, P. W.; Martin, J. N.; Sinclair, E; Bredt, B; Hagos, E; Lampiris, H; Deeks, S. G. (2003). "T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy". The Journal of Infectious Diseases. 187 (10): 1534–43. doi:10.1086/374786. PMID 12721933.
^Kaufmann, G. R.; Perrin, L; Pantaleo, G; Opravil, M; Furrer, H; Telenti, A; Hirschel, B; Ledergerber, B; Vernazza, P; Bernasconi, E; Rickenbach, M; Egger, M; Battegay, M; Swiss HIV Cohort Study Group (2003). "CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: The Swiss HIV Cohort Study". Archives of Internal Medicine. 163 (18): 2187–95. doi:10.1001/archinte.163.18.2187. PMID 14557216.
^Lori, F.; Foli, A.; Groff, A.; Lova, L.; Whitman, L.; Bakare, N.; Pollard, R.; Lisziewicz, J. (2005). "Optimal suppression of HIV replication by low-dose hydroxyurea through the combination of antiviral and cytostatic ('virostatic') mechanisms". AIDS. 19 (11): 1173–1181. doi:10.1097/01.aids.0000176217.02743.d1. PMID 15990570. S2CID 25239001.
^ ab . ViroStatics. Archived from the original on 2011-07-17. Retrieved 2011-09-22.
December 20, 2023
halt, antiviral, hyperactivation, limiting, therapeutics, investigational, class, antiretroviral, drugs, used, treat, human, immunodeficiency, virus, infection, unlike, other, antiretroviral, agents, given, reduce, viral, replication, single, combination, drug. AntiViral HyperActivation Limiting Therapeutics AV HALTs are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus HIV infection Unlike other antiretroviral agents given to reduce viral replication AV HALTs are single or combination drugs designed to reduce the rate of viral replication while at the same time also directly reducing the state of immune system hyperactivation now believed to drive the loss of CD4 T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome AIDS Contents 1 Mechanism 2 Examples 3 Synonyms 4 ReferencesMechanism editChronic immune stimulation due to persistent HIV replication and microbial translocation across impaired gut associated lymphoid tissues GALT induces continuous T cell activation and proliferation of both HIV infected and bystander cells ultimately resulting in the exhaustion of the immune system 1 2 3 4 5 6 There is a growing recognition that successful long term therapy for the treatment of HIV infection should not only reduce viral replication but also limit the hyper activation of the immune system now proposed as the cause of the eventual progression to AIDS 7 8 9 10 AV HALTs are designed to accomplish two goals the reduction of viral load decreased viral load and the reduction of immune system hyperactivation decreased markers of cellular activation and proliferation First generation AV HALTs accomplish this by combining an antiviral drug e g didanosine with a cytostatic agent e g hydroxyurea 11 Examples editVS411 investigational first generation combination AV HALT low dose hydroxyurea didanosine Phase II ViroStatics srl 12 VS1 002 investigational second generation single drug AV HALT Pre clinical ViroStatics srl 12 Synonyms editvirostatics antiVIRal cytOSTATICS References edit Ameisen J C Capron A 1991 Cell dysfunction and depletion in AIDS The programmed cell death hypothesis Immunology Today 12 4 102 5 doi 10 1016 0167 5699 91 90092 8 PMID 1676268 McCune J M 2001 The dynamics of CD4 T cell depletion in HIV disease Nature 410 6831 974 9 Bibcode 2001Natur 410 974M doi 10 1038 35073648 PMID 11309627 S2CID 4419786 Meyaard L Otto S A Keet I P Roos M T Miedema F 1994 Programmed death of T cells in human immunodeficiency virus infection No correlation with progression to disease Journal of Clinical Investigation 93 3 982 988 doi 10 1172 JCI117105 PMC 294014 PMID 8132784 Grossman Z Paul W E 2000 The impact of HIV on naive T cell homeostasis Nature Medicine 6 9 976 7 doi 10 1038 79667 PMID 10973313 S2CID 21350300 Hellerstein M K Hoh R A Hanley M B Cesar D Lee D Neese R A McCune J M 2003 Subpopulations of long lived and short lived T cells in advanced HIV 1 infection Journal of Clinical Investigation 112 6 956 66 doi 10 1172 JCI17533 PMC 193663 PMID 12975480 Finkel T H Tudor Williams G Banda N K Cotton M F Curiel T Monks C Baba T W Ruprecht R M Kupfer A 1995 Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV and SIV infected lymph nodes Nature Medicine 1 2 129 34 doi 10 1038 nm0295 129 PMID 7585008 S2CID 37444589 Brenchley J M Price D A Schacker T W Asher T E Silvestri G Rao S Kazzaz Z Bornstein E Lambotte O Altmann D Blazar B R Rodriguez B Teixeira Johnson L Landay A Martin J N Hecht F M Picker L J Lederman M M Deeks S G Douek D C 2006 Microbial translocation is a cause of systemic immune activation in chronic HIV infection Nature Medicine 12 12 1365 71 doi 10 1038 nm1511 PMC 1717013 PMID 17115046 Douek D C 2003 Disrupting T cell homeostasis How HIV 1 infection causes disease AIDS Reviews 5 3 172 7 PMID 14598566 Hunt P W Martin J N Sinclair E Bredt B Hagos E Lampiris H Deeks S G 2003 T cell activation is associated with lower CD4 T cell gains in human immunodeficiency virus infected patients with sustained viral suppression during antiretroviral therapy The Journal of Infectious Diseases 187 10 1534 43 doi 10 1086 374786 PMID 12721933 Kaufmann G R Perrin L Pantaleo G Opravil M Furrer H Telenti A Hirschel B Ledergerber B Vernazza P Bernasconi E Rickenbach M Egger M Battegay M Swiss HIV Cohort Study Group 2003 CD4 T lymphocyte recovery in individuals with advanced HIV 1 infection receiving potent antiretroviral therapy for 4 years The Swiss HIV Cohort Study Archives of Internal Medicine 163 18 2187 95 doi 10 1001 archinte 163 18 2187 PMID 14557216 Lori F Foli A Groff A Lova L Whitman L Bakare N Pollard R Lisziewicz J 2005 Optimal suppression of HIV replication by low dose hydroxyurea through the combination of antiviral and cytostatic virostatic mechanisms AIDS 19 11 1173 1181 doi 10 1097 01 aids 0000176217 02743 d1 PMID 15990570 S2CID 25239001 a b Research and Development ViroStatics Archived from the original on 2011 07 17 Retrieved 2011 09 22 Retrieved from https en wikipedia org w index php title AV HALT amp oldid 1171074718, wikipedia, wiki, book, books, library,
