PISCES - Primary Infection CNS Events Study
In the setting of primary HIV infection (within 6 months of acquisition), up to 10% of persons develop neurological signs and symptoms, and HIV can be detected in both cerebrospinal fluid (CSF) and brain tissue in virtually all of those infected. The mechanism of this initial neuroinvasion, and its significance for the natural history of systemic infection and the ultimate development of neurological disorders, are poorly understood.
It is thought that host responses of immune activation and inflammation are largely responsible for tissue injury. By examining the interplay between virus and host immune response early in HIV infection we hope to gain insight into mitigating or reversing neuronal and synaptic injury.
The primary goal of PISCES was to longitudinally define CNS host responses and viral features during primary HIV infection through serial clinical, CSF, and MRI/MRS analyses. Study of CSF allows for the analysis of host CNS responses to infection as well as characterization of potentially distinct populations of the virus residing in the CNS. Such viral characteristics in primary infection will reveal patterns of viral dynamics, mechanisms of inter-compartmental exchange, and time course of establishment of independent infection in the CNS.
PISCES is closed to enrollment.
It is thought that host responses of immune activation and inflammation are largely responsible for tissue injury. By examining the interplay between virus and host immune response early in HIV infection we hope to gain insight into mitigating or reversing neuronal and synaptic injury.
The primary goal of PISCES was to longitudinally define CNS host responses and viral features during primary HIV infection through serial clinical, CSF, and MRI/MRS analyses. Study of CSF allows for the analysis of host CNS responses to infection as well as characterization of potentially distinct populations of the virus residing in the CNS. Such viral characteristics in primary infection will reveal patterns of viral dynamics, mechanisms of inter-compartmental exchange, and time course of establishment of independent infection in the CNS.
PISCES is closed to enrollment.
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SPONSOR:
National Institute of Mental Health/NIH/DHHS |
COLLABORATORS:
University of California, San Francisco, USA University of Gothenburg, Gothenburg, Sweden University of Milan, Milan, Italy University of North Carolina, Chapel Hill, USA Washington University in St. Louis, USA |
SELECTED PUBLICATIONS (see Publications):
Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir? Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, Gisslén M. J Infect Dis. 2018 Feb 1. doi: 10.1093/infdis/jix662. [Epub ahead of print]. PMID: 29401308
Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls. Yilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, Spudich S, Underwood J, Zetterberg H, Gisslén M. Expert Rev Mol Diagn. 2017 Aug;17(8):761-770. doi: 10.1080/14737159.2017.1341313. Epub 2017 Jun 14. PMID: 28598205
Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. Rahimy E, Li FY, Hagberg L, Fuchs D, Robertson K, Meyerhoff DJ, Zetterberg H, Price RW, Gisslén M, Spudich S. J Infect Dis. 2017 Apr 1;215(7):1132-1140. doi: 10.1093/infdis/jix013. PMID: 28368497
Putamen volume and its clinical and neurological correlates in primary HIV infection. Wright PW, Pyakurel A, Vaida FF, Price RW, Lee E, Peterson J, Fuchs D, Zetterberg H, Robertson KR, Walter R, Meyerhoff DJ, Spudich SS, Ances BM. AIDS. 2016 Jul 17;30(11):1789-94. doi: 10.1097/QAD.0000000000001103. PMID: 27045376
Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection. Gega A, Kozal MJ, Chiarella J, Lee E, Peterson J, Hecht FM, Liegler T, St John EP, Simen BB, Price RW, Spudich SS. J Virus Erad. 2015;1(4):264-268. PMID: 26855971
Immune activation in the central nervous system throughout the course of HIV infection. Spudich SS. Curr Opin HIV AIDS. 2016 Mar;11(2):226-33. doi: 10.1097/COH.0000000000000243. Review. PMID: 26760827
Neurosyphilis and the impact of HIV infection. Ho EL, Spudich SS. Sex Health. 2015 Apr;12(2):148-54. doi: 10.1071/SH14195. PMID: 25890619
Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. PLoS Pathog. 2015 Mar 26;11(3):e1004720. doi: 10.1371/journal.ppat.1004720. eCollection 2015 Mar. PMID: 25811757
Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. Peterson J, Gisslen M, Zetterberg H, Fuchs D, Shacklett BL, Hagberg L, Yiannoutsos CT, Spudich SS, Price RW. PLoS One. 2014 Dec 26;9(12):e116081. doi: 10.1371/journal.pone.0116081. eCollection 2014. PMID: 25541953
Cerebral white matter integrity during primary HIV infection. Wright PW, Vaida FF, Fernández RJ, Rutlin J, Price RW, Lee E, Peterson J, Fuchs D, Shimony JS, Robertson KR, Walter R, Meyerhoff DJ, Spudich S, Ances BM. AIDS. 2015 Feb 20;29(4):433-42. doi: 10.1097/QAD.0000000000000560. PMID: 25513818
Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection. Suh J, Sinclair E, Peterson J, Lee E, Kyriakides TC, Li FY, Hagberg L, Fuchs D, Price RW, Gisslen M, Spudich S. J Neuroinflammation. 2014 Dec 3;11:199. doi: 10.1186/s12974-014-0199-y. PMID: 25465205
Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Young AC, Yiannoutsos CT, Hegde M, Lee E, Peterson J, Walter R, Price RW, Meyerhoff DJ, Spudich S. Neurology. 2014 Oct 28;83(18):1592-600. doi: 10.1212/WNL.0000000000000932. Epub 2014 Sep 26. PMID: 25261502
Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation. Wang SX, Ho EL, Grill M, Lee E, Peterson J, Robertson K, Fuchs D, Sinclair E, Price RW, Spudich S. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):303-10. doi: 10.1097/QAI.0000000000000167. PMID: 24732871
Evolving character of chronic central nervous system HIV infection. Price RW, Spudich SS, Peterson J, Joseph S, Fuchs D, Zetterberg H, Gisslén M, Swanstrom R. Semin Neurol. 2014 Feb;34(1):7-13. doi: 10.1055/s-0034-1372337. Epub 2014 Apr 8. Review. PMID: 24715483
Longitudinal characterization of depression and mood states beginning in primary HIV infection. Gold JA, Grill M, Peterson J, Pilcher C, Lee E, Hecht FM, Fuchs D, Yiannoutsos CT, Price RW, Robertson K, Spudich S. AIDS Behav. 2014 Jun;18(6):1124-32. doi: 10.1007/s10461-013-0688-5. PMID: 24385231
An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy. Dahl V, Gisslen M, Hagberg L, Peterson J, Shao W, Spudich S, Price RW, Palmer S. J Infect Dis. 2014 May 15;209(10):1618-22. doi: 10.1093/infdis/jit805. Epub 2013 Dec 12. PMID: 24338353
Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, Walter R, Fuchs D, Brew BJ, Cinque P, Robertson K, Hagberg L, Zetterberg H, Gisslén M, Spudich S. J Infect Dis. 2013 Jun 1;207(11):1703-12. doi: 10.1093/infdis/jit088. Epub 2013 Mar 4. PMID: 23460748
Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. Spudich S, Gisslen M, Hagberg L, Lee E, Liegler T, Brew B, Fuchs D, Tambussi G, Cinque P, Hecht FM, Price RW. J Infect Dis. 2011 Sep 1;204(5):753-60. doi: 10.1093/infdis/jir387. PMID: 21844301
Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. Schnell G, Price RW, Swanstrom R, Spudich S. J Virol. 2010 Mar;84(5):2395-407. doi: 10.1128/JVI.01863-09. Epub 2009 Dec 16. PMID: 20015984
Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir? Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, Gisslén M. J Infect Dis. 2018 Feb 1. doi: 10.1093/infdis/jix662. [Epub ahead of print]. PMID: 29401308
Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls. Yilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, Spudich S, Underwood J, Zetterberg H, Gisslén M. Expert Rev Mol Diagn. 2017 Aug;17(8):761-770. doi: 10.1080/14737159.2017.1341313. Epub 2017 Jun 14. PMID: 28598205
Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. Rahimy E, Li FY, Hagberg L, Fuchs D, Robertson K, Meyerhoff DJ, Zetterberg H, Price RW, Gisslén M, Spudich S. J Infect Dis. 2017 Apr 1;215(7):1132-1140. doi: 10.1093/infdis/jix013. PMID: 28368497
Putamen volume and its clinical and neurological correlates in primary HIV infection. Wright PW, Pyakurel A, Vaida FF, Price RW, Lee E, Peterson J, Fuchs D, Zetterberg H, Robertson KR, Walter R, Meyerhoff DJ, Spudich SS, Ances BM. AIDS. 2016 Jul 17;30(11):1789-94. doi: 10.1097/QAD.0000000000001103. PMID: 27045376
Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection. Gega A, Kozal MJ, Chiarella J, Lee E, Peterson J, Hecht FM, Liegler T, St John EP, Simen BB, Price RW, Spudich SS. J Virus Erad. 2015;1(4):264-268. PMID: 26855971
Immune activation in the central nervous system throughout the course of HIV infection. Spudich SS. Curr Opin HIV AIDS. 2016 Mar;11(2):226-33. doi: 10.1097/COH.0000000000000243. Review. PMID: 26760827
Neurosyphilis and the impact of HIV infection. Ho EL, Spudich SS. Sex Health. 2015 Apr;12(2):148-54. doi: 10.1071/SH14195. PMID: 25890619
Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. PLoS Pathog. 2015 Mar 26;11(3):e1004720. doi: 10.1371/journal.ppat.1004720. eCollection 2015 Mar. PMID: 25811757
Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. Peterson J, Gisslen M, Zetterberg H, Fuchs D, Shacklett BL, Hagberg L, Yiannoutsos CT, Spudich SS, Price RW. PLoS One. 2014 Dec 26;9(12):e116081. doi: 10.1371/journal.pone.0116081. eCollection 2014. PMID: 25541953
Cerebral white matter integrity during primary HIV infection. Wright PW, Vaida FF, Fernández RJ, Rutlin J, Price RW, Lee E, Peterson J, Fuchs D, Shimony JS, Robertson KR, Walter R, Meyerhoff DJ, Spudich S, Ances BM. AIDS. 2015 Feb 20;29(4):433-42. doi: 10.1097/QAD.0000000000000560. PMID: 25513818
Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection. Suh J, Sinclair E, Peterson J, Lee E, Kyriakides TC, Li FY, Hagberg L, Fuchs D, Price RW, Gisslen M, Spudich S. J Neuroinflammation. 2014 Dec 3;11:199. doi: 10.1186/s12974-014-0199-y. PMID: 25465205
Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Young AC, Yiannoutsos CT, Hegde M, Lee E, Peterson J, Walter R, Price RW, Meyerhoff DJ, Spudich S. Neurology. 2014 Oct 28;83(18):1592-600. doi: 10.1212/WNL.0000000000000932. Epub 2014 Sep 26. PMID: 25261502
Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation. Wang SX, Ho EL, Grill M, Lee E, Peterson J, Robertson K, Fuchs D, Sinclair E, Price RW, Spudich S. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):303-10. doi: 10.1097/QAI.0000000000000167. PMID: 24732871
Evolving character of chronic central nervous system HIV infection. Price RW, Spudich SS, Peterson J, Joseph S, Fuchs D, Zetterberg H, Gisslén M, Swanstrom R. Semin Neurol. 2014 Feb;34(1):7-13. doi: 10.1055/s-0034-1372337. Epub 2014 Apr 8. Review. PMID: 24715483
Longitudinal characterization of depression and mood states beginning in primary HIV infection. Gold JA, Grill M, Peterson J, Pilcher C, Lee E, Hecht FM, Fuchs D, Yiannoutsos CT, Price RW, Robertson K, Spudich S. AIDS Behav. 2014 Jun;18(6):1124-32. doi: 10.1007/s10461-013-0688-5. PMID: 24385231
An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy. Dahl V, Gisslen M, Hagberg L, Peterson J, Shao W, Spudich S, Price RW, Palmer S. J Infect Dis. 2014 May 15;209(10):1618-22. doi: 10.1093/infdis/jit805. Epub 2013 Dec 12. PMID: 24338353
Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, Walter R, Fuchs D, Brew BJ, Cinque P, Robertson K, Hagberg L, Zetterberg H, Gisslén M, Spudich S. J Infect Dis. 2013 Jun 1;207(11):1703-12. doi: 10.1093/infdis/jit088. Epub 2013 Mar 4. PMID: 23460748
Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. Spudich S, Gisslen M, Hagberg L, Lee E, Liegler T, Brew B, Fuchs D, Tambussi G, Cinque P, Hecht FM, Price RW. J Infect Dis. 2011 Sep 1;204(5):753-60. doi: 10.1093/infdis/jir387. PMID: 21844301
Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. Schnell G, Price RW, Swanstrom R, Spudich S. J Virol. 2010 Mar;84(5):2395-407. doi: 10.1128/JVI.01863-09. Epub 2009 Dec 16. PMID: 20015984