Skip to main content

Advertisement

SpringerLink
Log in

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.

The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abdulle S, Hagberg L, Gisslén M (2005) Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients. HIV Medicine 6:164–169

    Article  CAS  PubMed  Google Scholar 

  • Andersson MA, Bergström TB, Blomstrand C, Hermodsson SH, Håkansson C, Löwhagen GB (1988) Increasing intrathecal lymphocytosis and immunoglobulin G production in neurologically asymptomatic HIV-1 infection. J Neuroimmunol 19:291–304

    Article  CAS  PubMed  Google Scholar 

  • Andersson LM, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J, Fredrikson S, Gallo P, Grimaldi LM, Grønning M (1994) Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. Journal of Neurology, neurosurgery, Psychiatry 57:897–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berkeley JL, Nath A, Pardo CA (2008) Fatal immune reconstitution inflammatory syndrome with human immunodeficiency virus infection and Candida meningitis: case report and review of the literature. Journal of Neurovirology 14:267–276

    Article  CAS  PubMed  Google Scholar 

  • Bingham R, Ahmed N, Rangi P, Johnson M, Tyrer M, Green J (2011) HIV encephalitis despite suppressed viraemia: a case of compartmentalized viral escape. Int J STD AIDS 22:608–609

    Article  CAS  PubMed  Google Scholar 

  • Bogoch II, Davis BT, Venna N (2011) Reversible dementia in a patient with central nervous system escape of human immunodeficiency virus. J Infect 63:236–239

    Article  PubMed  Google Scholar 

  • Breebaart K, Becker H, Jongebloed FA (1978) Investigation of reference values of components of cerebrospinal fluid. J Clin Chem Clin Biochem 16:561–565

    CAS  PubMed  Google Scholar 

  • Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, Peytavin G, Tubiana R, Pialoux G, Katlama C (2010) Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50:773–778

    Article  PubMed  Google Scholar 

  • Caroscio JT, Kochwa S, Sacks H, Cohen JA, Yahr MD (1983) Quantitative CSF IgG measurements in multiple sclerosis and other neurological diseases. Arch Neurol 40:409–413

    Article  CAS  PubMed  Google Scholar 

  • Carter CC, Wagner GA, Hightower GK, Caballero G, Phung P, Richman DD, Pond SL, Smith DM (2015) HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing. Virology 474:34–40

    Article  CAS  PubMed  Google Scholar 

  • Caudie C, Bancel J, Dupont M, Matanza D, Poitevin F, Honnorat J (2005) CSF levels and diagnostic utility of cerebrospinal fluid beta2-microglobulin. Ann Biol Clin 63:631–637

    CAS  Google Scholar 

  • Chen W, Wang H (2015) Variance estimation for nucleotide substitution models. Mol Phylogenet Evol 90:97–103

    Article  CAS  PubMed  Google Scholar 

  • de Almeida SM, Ribeiro CE, de Pereira AP, Badiee J, Cherner M, Smith D, Maich I, Raboni SM, Rotta I, Barbosa FJ, Heaton RK, Umlauf A, Ellis RJ (2013) Neurocognitive impairment in HIV-1 subtype C- versus B-infected individuals in Southern Brazil. J Neurovirol 19:550–556

    Article  PubMed  PubMed Central  Google Scholar 

  • de Almeida SM, Rotta I, Jiang Y, Li X, Raboni SM, Ribeiro CE, Smith D, Vaida F, Letendre S, Ellis RJ (2016a) Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B. J Neurovirol 22:715–724. doi:10.1007/s13365-016-0437-4

    Article  PubMed  Google Scholar 

  • de Almeida SM, Rotta I, Ribeiro CE, Smith D, Wang R, Judicello J, Potter M, Vaida F, Letendre S, Ellis R (2016b) Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection. J Neuroimmunol. doi:10.1016/j.jneuroim.2016.10.009 [Epub ahead of print]

    PubMed  Google Scholar 

  • Edén A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M (2007) Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy. Journal of Infectious Disease 196:1779–1783

    Article  Google Scholar 

  • Edgar RC (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5:113

    Article  PubMed  PubMed Central  Google Scholar 

  • Elovaara I, Iivanainen M, Valle SL, Suni J, Tervo T, Lähdevirta J (1987) CSF protein and cellular profiles in various stages of HIV infection related to neurological manifestations. J Neurol Sci 78:331–342

    Article  CAS  PubMed  Google Scholar 

  • Fisher RG, Smith DM, Murrell B, Slabbert R, Kirby BM, Edson C, Cotton MF, Haubrich RH, Kosakovsky Pond SL, Van Zyl GU (2015) Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure. J Clin Virol 62:48–53

    Article  CAS  PubMed  Google Scholar 

  • Gallo P, de Rossi A, Cadrobbi P, Francavilla E, Chieco-Bianchi L, Tavolato B (1988) Intrathecal synthesis of anti-H1V oligoclonal IgG in H1V-seropositive patients having no signs of H1V-induced neurological diseases. Ann N Y Acad Sci 540:615–618

    Article  CAS  PubMed  Google Scholar 

  • Gallo P, Frei K, Rordorf C, Lazdins J, Tavolato B, Fontana A (1989) Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. J Neuroimmunol 23:109–116

    Article  CAS  PubMed  Google Scholar 

  • Goswami KK, Kaye S, Miller R, McAllister R, Tedder R (1991) Intrathecal IgG synthesis and specificity of oligoclonal IgG in patients infected with HIV-1 do not correlate with CNS disease. J Med Virol 33:106–113

    Article  CAS  PubMed  Google Scholar 

  • Goudsmit J, Wolters EC, Bakker M, Smit L, Van der Noordaa J, Hische EA, Tutuarima JA, Van der Helm HJ (1986) Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex. Br Med J (Clin Res Ed) 292:1231–1234

    Article  CAS  Google Scholar 

  • Granger C, Hamilton B (1987) Development of a uniform national data system for medical rehabilitation 1984–97. Final report for grant number G008435062. Buffalo: National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitative Services, Department of Education

  • Greene DN, Schmidt RL, Wilson AR, Freedman MS, Grenache DG (2012) Cerebrospinal fluid myelin basic protein is frequently ordered but has little value, a test utilization study. Am J Clin Pathol 138:262–272

    Article  PubMed  Google Scholar 

  • Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704

    Article  PubMed  Google Scholar 

  • Haggerty S, Stevenson M (1991) Predominance of distinct viral genotypes in brain and lymph node compartments of HIV-1-infected individuals. Viral Immunol 4:123–131

    Article  CAS  PubMed  Google Scholar 

  • Harrington PR, Haas DW, Ritola K, Swanstrom R (2005) Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal fluid is produced by short-lived cells. J Virol 79:7959–7966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington PR, Schnell G, Letendre SL, Ritola K, Robertson K, Hall C, Burch CL, Jabara CB, Moore DT, Ellis RJ, Price RW, Swanstrom R (2009) Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS 23:907–915

    Article  PubMed  PubMed Central  Google Scholar 

  • Hudson RR, Slatkin M, Maddison WP (1992) Estimation of levels of gene flow from DNA sequence data. Genetics 132:583–589

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jacque C, Delassalle A, Rancurel G, Raoul M, Lesourd B, Legrand JC (1982) Myelin basic protein in CSF and blood, relationship between its presence and the occurrence of a destructive process in the brains of encephalitic patients. Arch Neurol 39:557–560

    Article  CAS  PubMed  Google Scholar 

  • Johnson T, Nath A (2010) Neurological complications of immune reconstitution in HIV-infected populations. Ann N Y Acad Sci 1184:106–120

    Article  CAS  PubMed  Google Scholar 

  • Karris M, Smith DM (2011) Tissue-specific HIV-1 infection: why it matters. Future Virol 6:869–882

    Article  PubMed  PubMed Central  Google Scholar 

  • Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P (2010) Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS 24:2365–2374

    CAS  PubMed  Google Scholar 

  • Langford TD, Letendre SL, Marcotte TD, et al. (2002) Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy. AIDS 16:1019–2

  • Lescure FX, Moulignier A, Savatovsky J, Amiel C, Carcelain G, Molina JM, Gallien S, Pacanovski J, Pialoux G, Adle-Biassette H, Gray F (2013) CD8 encephalitis in HIV-infected patients receiving cART: a treatable entity. Clin Infect Dis 57:101–108

    Article  CAS  PubMed  Google Scholar 

  • Letendre S, Ellis R, Deutsch R, Clifford D, Marra C, McCutchan A, Morgello S, Simpson D, Heaton R, Grant I, the CHARTER Group (2010) Correlates of time-to-loss-of-viral response in CSF and plasma in the CHARTER cohort. Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, CA. 16–19 February (poster 430)

  • Lipman M, Breen R (2006) Immune reconstitution inflammatory syndrome in HIV. Curr Opin Infect Dis 19:20–25

    Article  PubMed  Google Scholar 

  • Liuzzi GM, Mastroianni CM, Vullo V, Jirillo E, Delia S, Riccio P (1992) Cerebrospinal fluid myelin basic protein as predictive marker of demyelination in AIDS dementia complex. J Neuroimmunol 36:251–254

    Article  CAS  PubMed  Google Scholar 

  • Marshall DW, Brey RL, Butzin CA, Lucey DR, Abbadessa SM, Boswell RN (1991) CSF changes in a longitudinal study of 124 neurologically normal HIV-1-infected U.S. Air Force personnel. J Acquir Immune Defic Syndr 4:777–781

    CAS  PubMed  Google Scholar 

  • McArthur JC, Cohen BA, Farzedegan H, Cornblath DR, Selnes OA, Ostrow D, Johnson RT, Phair J, Polk BF (1988) Cerebrospinal fluid abnormalities in homosexual men with and without neuropsychiatric findings. Ann Neurol 23:–37

  • Miller RF, Isaacson PG, Hall-Craggs M, Lucas S, Gray F, Scaravilli F, An SF (2004) Cerebral CD8+ lymphocytosis in HIV-1 infected patients with immune restoration induced by HAART. Acta Neuropathol 108:17–23

    Article  PubMed  Google Scholar 

  • Murdoch DM, Venter WDF, Van Rie A, Feldman C (2007) Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther 4:9

    Article  PubMed  PubMed Central  Google Scholar 

  • North TW, Higgins J, Deere JD, Hayes TL, Villalobos A, Adamson L, Shacklett BL, Schinazi RF, Luciw PA (2010) Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. J Virol 84:2913–2922

    Article  CAS  PubMed  Google Scholar 

  • Palacio D, Tamarit M, Quereda C, Gonzalez-Rozas M, Corral I, Casado JL (2012) HIV type 1 viral encephalitis after development of viral resistance to plasma suppressive antiretroviral therapy. AIDS Res Hum Retrovir 28:83–86

    Article  Google Scholar 

  • Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A, Gisslén M, Angoff N, Price RW, Cinque P, Spudich S (2012) Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well-controlled plasma viral load. AIDS 26(14):1765–1774

  • Petzold A, Eikelenboom MJ, Gveric D, Keir G, Chapman M, Lazeron RH, Cuzner ML, Polman CH, Uitdehaag BM, Thompson EJ, Giovannoni G (2002) Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 125:1462–1473

    Article  CAS  PubMed  Google Scholar 

  • Pfister HW, Einhäupl KM, Wick M, Fateh-Moghadam A, Huber M, Schielke E, Goebel FD, Matuschke A, Heinrich B, Bogner JR (1989) Myelin basic protein in the cerebrospinal fluid of patients infected with HIV. J Neurol 236:288–291

    Article  CAS  PubMed  Google Scholar 

  • Ranga U, Shankarappa R, Siddapa NB, Ramakrishna L, Nagendran R, Mahalingam M, Mahadevan A, Jayasuryan N, Satishchandra P, Shankar SK, Prasad VR (2004) Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J Virology 78:2586–2590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reboul J, Schuller E, Pialoux G, Rey MA, Lebon P, Allinquant B, Brun-Vezinet F (1989) Immunoglobulins and complement components in 37 patients infected by HIV-1 virus: comparison of general (systemic) and intrathecal immunity. J Neurol Sci 89:243–252

    Article  CAS  PubMed  Google Scholar 

  • Reiber H (1995) External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients. Clin Chem 41:256–263

    CAS  PubMed  Google Scholar 

  • Reiber H, Peter JB (2001) Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci 184:101–122

    Article  CAS  PubMed  Google Scholar 

  • Resnick L, Berger JR, Shapshak P, Tourtellotte WW (1998) Early penetration of the blood brain barrier by HIV. Neurology 38:9–14

    Article  Google Scholar 

  • Riedel DJ, Pardo CA, McArthur J, Nath A (2006) CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome. Nat Clin Pract Neurol 2:557–565

    Article  PubMed  Google Scholar 

  • Ritola K, Robertson K, Fiscus SA, Hall C, Swanstrom R (2005) Increased human immunodeficiency virus type 1 (HIV-1) env compartmentalization in the presence of HIV-1-associated dementia. J Virol 79:10830–10834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rotta I, Raboni SM, Ribeiro CEL, Riedel M, Winhescki MG, Smith DM, Ellis RJ, de Almeida SM (2014) Cerebrospinal fluid can be used for HIV genotyping when it fails in blood. Arquivos de Neuro-Psiquiatria 72(7):506–509

  • Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, Robertson K, McArthur JC, Ronald A, Katabira E (2005) The international HIV dementia scale: a new rapid screening test for HIV dementia. AIDS 19:1367–1374

    PubMed  Google Scholar 

  • Satishchandra P, Nalini A, Gourie-Devi M, Khanna N, Santosh V, Rasvi V, Desai A, Chandramuki A, Jayakumar PN, Shankar SK (2000) Profile of neurologic disorders associated with HIV/AIDS from Bangalore, South India (1989-96). Indian J Med Res 111:14–23

    CAS  PubMed  Google Scholar 

  • Schnell G, Price RW, Swanstrom R, Spudich S (2010) Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J Virol 84:2395–2407

    Article  CAS  PubMed  Google Scholar 

  • Sönnerborg AB, von Sydow MA, Forsgren M, Strannegård OO (1989) Association between intrathecal anti-HIV-1 immunoglobulin G synthesis and occurrence of HIV-1 in cerebrospinal fluid. AIDS 3:701–705

    Article  PubMed  Google Scholar 

  • Subsai K, Kanoksri S, Siwaporn C, Helen L, Kanokporn O, Wantana P (2006) Neurological complications in AIDS patients receiving HAART: a 2-year retrospective study. Eur J Neurol 13:233–239

    Article  CAS  PubMed  Google Scholar 

  • Tourtellotte WW (1970) On cerebrospinal fluid immunoglobulin-G (IgG) quotients in multiple sclerosis and other diseases. A review and a new formula to estimate the amount of IgG synthesized per day by the central nervous system. J Neurol Sci 10:279–304

    Article  CAS  PubMed  Google Scholar 

  • Tourtellotte WW, Shapshak P, Osborne MA, Rubinshtein G, Lee M, Staugaitis K (1989) New Fomula to calculate the rate of albumin blood brain barrier leakage. Ann Neurol 26:176

    Google Scholar 

  • van Lelyveld SF, Nijhuis M, Baatz F, Wilting I, van den Bergh WM, Kurowski M, de Jong D, Hoepelman AI, Wensing AM (2010) Therapy failure following selection of enfuvirtide resistant HIV-1 in cerebrospinal fluid. Clin Infect Dis 50:387–390

    Article  PubMed  Google Scholar 

  • Venkataramana A, Pardo CA, McArthur JC, Kerr DA, Irani DN, Griffin JW, Burger P, Reich DS, Calabresi PA, Nath A (2006) Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients. Neurology 67:383–388

    Article  CAS  PubMed  Google Scholar 

  • Wagner GA, Pacold ME, Kosakovsky Pond SL, Caballero G, Chaillon A, Rudolph AE, Morris SR, Little SJ, Richman DD, Smith DM (2014) Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States. J Infect Dis 209:1032–1038

    Article  CAS  PubMed  Google Scholar 

  • Zarate S, Pond SLK, Shapshak P, Frost SDW (2007) Comparative study of methods for detecting sequence compartmentalization in human immunodeficiency virus type 1. J Virol 81:6643–6651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Professor Albert Anderson, Emory School of Medicine, Atlanta, USA.

Author information

Authors and Affiliations

  1. Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    Sergio M. de Almeida, Indianara Rotta, Clea E. Ribeiro, Ana Paula de Pereira, Ana Paula Cunha, Marise Zonta, Joao França Bents & Sonia M. Raboni

  2. Seção de Virologia, Setor Análises Clínicas, Hospital de Clínicas—UFPR, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil

    Sergio M. de Almeida

  3. Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil

    Sergio M. de Almeida & Indianara Rotta

  4. University of California, San Diego, San Diego, CA, USA

    Michelli F. Oliveira, Antoine Chaillon, Davey Smith, Scott Letendre & Ronald J. Ellis

Authors
  1. Sergio M. de Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Indianara Rotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Clea E. Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelli F. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antoine Chaillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Paula de Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Paula Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marise Zonta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joao França Bents
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sonia M. Raboni
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Davey Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Scott Letendre
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ronald J. Ellis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sergio M. de Almeida.

Ethics declarations

This study was approved by institutional review boards (IRB) at Hospital de Clínicas—UFPR in Brazil and Brazil National IRB (CONEP).

Funding

This work was supported by the following grants: National Institute of Health, NIH R21 MH76651 (Ellis, Ronald J.; Almeida, Sergio M.), NIH R01 MH83552 (Smith, David M.), S10 RR31646 (Letendre, Scott), and K24 MH097673 (Letendre, Scott); University of California, San Diego, Center for AIDS Research (CFAR), an NIH-funded program (P30 AI036214), which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK; and Ministério da Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico, MCT/CNPq-Universal 014/2008, Brazil (Almeida, Sergio M.).

The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 from NIMH. The San Diego HIV Neurobehavioral Research Center [HNRC] group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System and includes the following: Director: Robert K. Heaton, Ph.D.; Co-Director: Igor Grant, M.D.; Associate Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., Scott Letendre, M.D.; Center Managers: Thomas D. Marcotte, Ph.D., Jennifer Marquie-Beck, M.P.H., Melanie Sherman; Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), Scott Letendre, M.D., J. Allen McCutchan, M.D., Brookie Best, Pharm.D., Rachel Schrier, Ph.D., Debra Rosario, M.P.H.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), J. Hampton Atkinson, M.D., Steven Paul Woods, Psy.D., Thomas D. Marcotte, Ph.D., Mariana Cherner, Ph.D., David J. Moore, Ph.D., Matthew Dawson; Neuroimaging Component: Christine Fennema-Notestine, Ph.D. (P.I.), Monte S. Buchsbaum, M.D., John Hesselink, M.D., Sarah L. Archibald, M.A., Gregory Brown, Ph.D., Richard Buxton, Ph.D., Anders Dale, Ph.D., Thomas Liu, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Cristian Achim, M.D., Ph.D.; Neurovirology Component: David M. Smith, M.D. (P.I.), Douglas Richman, M.D.; International Component: J. Allen McCutchan, M.D. (P.I.), Mariana Cherner, Ph.D.; Developmental Component: Cristian Achim, M.D., Ph.D. (P.I.), Stuart Lipton, M.D., Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Jennifer Marquie-Beck, M.P.H.; Data Management and Information Systems Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman; and Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D. (Co-PI), Reena Deutsch, Ph.D., Anya Umlauf, M.S.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Figure S1

(DOC 214 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Almeida, S.M., Rotta, I., Ribeiro, C.E. et al. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization—case study. J. Neurovirol. 23, 460–473 (2017). https://doi.org/10.1007/s13365-017-0518-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-017-0518-z

Keywords

Search

Navigation