Top

Current HIV/AIDS Reports

Published in:

01-06-2022 | Human Immunodeficiency Virus | HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)

HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies

Authors: Phillip Chan, Serena Spudich

Published in: Current HIV/AIDS Reports | Issue 3/2022

Abstract

Purpose of Review

This review focuses on the cerebrospinal fluid (CSF) findings in connection to the central nervous system (CNS) reservoir in treatment-naïve and virally suppressed PLWH, followed by the findings in CSF HIV-1 escape and analytical treatment interruption studies.

Recent Findings

Compared to chronic infection, initiating antiretroviral therapy (ART) during acute HIV-1 infection results in more homogeneous longitudinal benefits in the CNS. Viral variants in CSF HIV-1 escape are independently linked to infected cells from the systemic reservoir and in the CNS, highlighting the phenomenon as a consequence of different mechanisms. HIV-infected cells persist in CSF in nearly half of the individuals on stable ART and are associated with worse neurocognitive performance.

Summary

Future studies should probe into the origin of the HIV-infected cells in the CSF. Examining the capacity for viral replication would provide new insight into the CNS reservoir and identify strategies to eradicate it or compensate for the insufficiency of ART.

Fromentin R, Chomont N. HIV persistence in subsets of CD4+ T cells: 50 shades of reservoirs. Semin Immunol. 2021;51:101438. https://doi.org/10.1016/j.smim.2020.101438.CrossRefPubMed

Wong JK, Yukl SA. Tissue reservoirs of HIV. Curr Opin HIV AIDS. 2016;11(4):362–70. https://doi.org/10.1097/COH.0000000000000293.CrossRefPubMedPubMedCentral

Lamers SL, Rose R, Maidji E, Agsalda-Garcia M, Nolan DJ, Fogel GB, et al. HIV DNA is frequently present within pathologic tissues evaluated at autopsy from combined antiretroviral therapy-treated patients with undetectable viral loads. J Virol. 2016;90(20):8968–83. https://doi.org/10.1128/JVI.00674-16.CrossRefPubMedPubMedCentral

Chaillon A, Gianella S, Dellicour S, Rawlings SA, Schlub TE, De Oliveira MF, et al. HIV persists throughout deep tissues with repopulation from multiple anatomical sources. J Clin Invest. 2020;130(4):1699–712. https://doi.org/10.1172/JCI134815.CrossRefPubMedPubMedCentral

Croese T, Castellani G, Schwartz M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol. 2021;22(9):1083–92. https://doi.org/10.1038/s41590-021-00994-2.CrossRefPubMed

Winston A, Antinori A, Cinque P, Fox HS, Gisslen M, Henrich TJ, et al. Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS. AIDS. 2019;33(Suppl 2):S107–11. https://doi.org/10.1097/QAD.0000000000002252.CrossRefPubMed

Joseph J, Cinque P, Colosi D, Dravid A, Ene L, Fox H, et al. Highlights of the global HIV-1 CSF escape consortium meeting, 9 June 2016, Bethesda, MD, USA. J Virus Erad. 2016;2(4):243–50.CrossRef

Perez-Valero I, Ellis R, Heaton R, Deutsch R, Franklin D, Clifford DB, et al. Cerebrospinal fluid viral escape in aviremic HIV-infected patients receiving antiretroviral therapy: prevalence, risk factors and neurocognitive effects. AIDS. 2019;33(3):475–81. https://doi.org/10.1097/QAD.0000000000002074.CrossRefPubMed

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99. https://doi.org/10.1212/01.WNL.0000287431.88658.8b.CrossRefPubMed

10.

•• Spudich S, Robertson KR, Bosch RJ, Gandhi RT, Cyktor JC, Mar H, et al. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. J Clin Invest. 2019;129(8):3339–46. https://doi.org/10.1172/JCI127413. (This work describes an unexpectedly high frequency of HIV-infected cells in the cerebrospinal fluid despite stable suppressive antiretroviral therapy.)CrossRefPubMedPubMedCentral

11.

Wallet C, De Rovere M, Van Assche J, Daouad F, De Wit S, Gautier V, et al. Microglial cells: the main HIV-1 reservoir in the brain. Front Cell Infect Microbiol. 2019;9:362. https://doi.org/10.3389/fcimb.2019.00362.CrossRefPubMedPubMedCentral

12.

Al-Harti L, Joseph J, Nath A. Astrocytes as an HIV CNS reservoir: highlights and reflections of an NIMH-sponsored symposium. J Neurovirol. 2018;24(6):665–9. https://doi.org/10.1007/s13365-018-0691-8.CrossRefPubMedPubMedCentral

13.

Chan P, Patel P, Hellmuth J, Colby DJ, Kroon E, Sacdalan C, et al. Distribution of HIV RNA in CSF and blood is linked to CD4/CD8 ratio during acute HIV. J Infect Dis. 2018. https://doi.org/10.1093/infdis/jiy260.CrossRefPubMedPubMedCentral

14.

Tovanabutra S, Sirijatuphat R, Pham PT, Bonar L, Harbolick EA, Bose M, et al. Deep sequencing reveals central nervous system compartmentalization in multiple transmitted/founder virus acute HIV-1 infection. Cells. 2019;8(8). https://doi.org/10.3390/cells8080902

15.

Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J Virol. 2010;84(5):2395–407. https://doi.org/10.1128/JVI.01863-09.CrossRefPubMed

16.

Gega A, Kozal MJ, Chiarella J, Lee E, Peterson J, Hecht FM, et al. Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection. J Virus Erad. 2015;1(4):264–8.CrossRef

17.

Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. PLoS Pathog. 2015;11(3):e1004720. https://doi.org/10.1371/journal.ppat.1004720.CrossRefPubMedPubMedCentral

18.

Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R. HIV-1 replication in the central nervous system occurs in two distinct cell types. PLoS Pathog. 2011;7(10):e1002286. https://doi.org/10.1371/journal.ppat.1002286.CrossRefPubMedPubMedCentral

19.

Ulfhammer G, Eden A, Antinori A, Brew BJ, Calcagno A, Cinque P, et al. Cerebrospinal fluid viral load across the spectrum of untreated HIV-1 infection: a cross-sectional multi-center study. Clin Infect Dis. 2021. https://doi.org/10.1093/cid/ciab943.CrossRefPubMed

20.

•• Gisslen M, Keating SM, Spudich S, Arechiga V, Stephenson S, Zetterberg H, et al. Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression. PLoS One. 2021;16(5):e0250987. https://doi.org/10.1371/journal.pone.0250987. (This work examines the evolution of the elevation of immune activation markers in the CSF across different stages of HIV infection.)CrossRefPubMedPubMedCentral

21.

Group ISS, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795–807. https://doi.org/10.1056/NEJMoa1506816.CrossRef

22.

Wright EJ, Grund B, Robertson KR, Cysique L, Brew BJ, Collins GL, et al. No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts. AIDS. 2018;32(8):985–97. https://doi.org/10.1097/QAD.0000000000001778.CrossRefPubMed

23.

Peluso MJ, Valcour V, Ananworanich J, Sithinamsuwan P, Chalermchai T, Fletcher JL, et al. Absence of cerebrospinal fluid signs of neuronal injury before and after immediate antiretroviral therapy in acute HIV infection. J Infect Dis. 2015;212(11):1759–67. https://doi.org/10.1093/infdis/jiv296.CrossRefPubMedPubMedCentral

24.

Ulfhammer G, Eden A, Mellgren A, Fuchs D, Zetterberg H, Hagberg L, et al. Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment. AIDS. 2018;32(15):2171–8. https://doi.org/10.1097/QAD.0000000000001950.CrossRefPubMed

25.

Garvey LJ, Pavese N, Politis M, Ramlackhansingh A, Brooks DJ, Taylor-Robinson SD, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. AIDS. 2014;28(1):67–72. https://doi.org/10.1097/01.aids.0000432467.54003.f7.CrossRefPubMed

26.

Vera JH, Guo Q, Cole JH, Boasso A, Greathead L, Kelleher P, et al. Neuroinflammation in treated HIV-positive individuals: a TSPO PET study. Neurology. 2016;86(15):1425–32. https://doi.org/10.1212/WNL.0000000000002485.CrossRefPubMedPubMedCentral

27.

Rubin LH, Sacktor N, Creighton J, Du Y, Endres CJ, Pomper MG, et al. Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy. AIDS. 2018;32(12):1661–7. https://doi.org/10.1097/QAD.0000000000001858.CrossRefPubMed

28.

Evering TH, Applebaum A, La Mar M, Garmon D, Dorfman D, Markowitz M. Rates of non-confounded HIV-associated neurocognitive disorders in men initiating combination antiretroviral therapy during primary infection. AIDS. 2016;30(2):203–10. https://doi.org/10.1097/QAD.0000000000000892.CrossRefPubMed

29.

Chan P, Kerr SJ, Kroon E, Colby D, Sacdalan C, Hellmuth J, et al. Cognitive trajectories after treatment in acute HIV infection. AIDS. 2021;35(6):883–8. https://doi.org/10.1097/QAD.0000000000002831.CrossRefPubMed

30.

Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, et al. Very early initiation of antiretroviral therapy during acute HIV infection is associated with normalized levels of immune activation markers in cerebrospinal fluid but not in plasma. J Infect Dis. 2019;220(12):1885–91. https://doi.org/10.1093/infdis/jiz030.CrossRefPubMedPubMedCentral

31.

•• Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, et al. Anti-human immunodeficiency virus antibodies in the cerebrospinal fluid: evidence of early treatment impact on central nervous system reservoir? J Infect Dis. 2018;217(7):1024–32. https://doi.org/10.1093/infdis/jix662. (This work demonstrated the association between early ART and significant level reductions of anti-HIV antibodies in blood and CSF. Given the level of anti-HIV antibodies correlates with the extent of antigen exposure, the findings suggest that early ART may reduce the long-term immune activation by limiting the size of the HIV reservoir.)CrossRefPubMedPubMedCentral

32.

DeMaster LK, Liu X, VanBelzen DJ, Trinite B, Zheng L, Agosto LM, et al. A subset of CD4/CD8 double-negative T cells expresses HIV proteins in patients on antiretroviral therapy. J Virol. 2015;90(5):2165–79. https://doi.org/10.1128/JVI.01913-15.CrossRefPubMed

33.

Imamichi H, Smith M, Adelsberger JW, Izumi T, Scrimieri F, Sherman BT, et al. Defective HIV-1 proviruses produce viral proteins. Proc Natl Acad Sci USA. 2020;117(7):3704–10. https://doi.org/10.1073/pnas.1917876117.CrossRefPubMedPubMedCentral

34.

Imamichi H, Dewar RL, Adelsberger JW, Rehm CA, O’Doherty U, Paxinos EE, et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci USA. 2016;113(31):8783–8. https://doi.org/10.1073/pnas.1609057113.CrossRefPubMedPubMedCentral

35.

Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, et al. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection. AIDS. 2021;35(5):777–82. https://doi.org/10.1097/QAD.0000000000002786.CrossRefPubMed

36.

Wendel KA, McArthur JC. Acute meningoencephalitis in chronic human immunodeficiency virus (HIV) infection: putative central nervous system escape of HIV replication. Clin Infect Dis. 2003;37(8):1107–11. https://doi.org/10.1086/378300.CrossRefPubMed

37.

Eden A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, et al. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis. 2010;202(12):1819–25. https://doi.org/10.1086/657342.CrossRefPubMedPubMedCentral

38.

Spudich S, Lollo N, Liegler T, Deeks SG, Price RW. Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure. J Infect Dis. 2006;194(12):1686–96. https://doi.org/10.1086/508750.CrossRefPubMed

39.

Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50(5):773–8. https://doi.org/10.1086/650538.CrossRefPubMed

40.

•• Chan TY, De Zan V, Gregg A, Alagaratnam J, Gerevini S, Antinori A, et al. The symptomatology of cerebrospinal fluid HIV RNA escape: a large case-series. AIDS. 2021;35(14):2341–6. https://doi.org/10.1097/QAD.0000000000002992. (This large case series illustrates the diversity in symptom onset and clinical manifestations of HIV CSF escape.)CrossRefPubMed

41.

Eden A, Nilsson S, Hagberg L, Fuchs D, Zetterberg H, Svennerholm B, et al. Asymptomatic cerebrospinal fluid HIV-1 viral blips and viral escape during antiretroviral therapy: a longitudinal study. J Infect Dis. 2016;214(12):1822–5. https://doi.org/10.1093/infdis/jiw454.CrossRefPubMed

42.

Ferretti F, De Zan V, Gerevini S, Turrini F, Boeri E, Gianotti N, et al. Relapse of symptomatic cerebrospinal fluid HIV escape. Curr HIV/AIDS Rep. 2020;17(5):522–8. https://doi.org/10.1007/s11904-020-00526-x.CrossRefPubMed

43.

Mukerji SS, Misra V, Lorenz DR, Uno H, Morgello S, Franklin D, et al. Impact of antiretroviral regimens on cerebrospinal fluid viral escape in a prospective multicohort study of antiretroviral therapy-experienced human immunodeficiency virus-1-infected adults in the United States. Clin Infect Dis. 2018;67(8):1182–90. https://doi.org/10.1093/cid/ciy267.CrossRefPubMedPubMedCentral

44.

Anderson AM, Munoz-Moreno JA, McClernon DR, Ellis RJ, Cookson D, Clifford DB, et al. Prevalence and correlates of persistent HIV-1 RNA in cerebrospinal fluid during antiretroviral therapy. J Infect Dis. 2017;215(1):105–13. https://doi.org/10.1093/infdis/jiw505.CrossRefPubMed

45.

Anderson AM, Tang B, Vaida F, McClernon D, Deutsch R, Cherner M, et al. Low-level HIV RNA in cerebrospinal fluid and neurocognitive performance: a longitudinal cohort study. J Acquir Immune Defic Syndr. 2021;87(5):1196–204. https://doi.org/10.1097/QAI.0000000000002714.CrossRefPubMed

46.

Nightingale S, Michael BD, Fisher M, Winston A, Nelson M, Taylor S, et al. CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF. Cytokine. 2016;83:139–46. https://doi.org/10.1016/j.cyto.2016.04.004.CrossRefPubMedPubMedCentral

47.

Mastrangelo A, Turrini F, de Zan V, Caccia R, Gerevini S, Cinque P. Symptomatic cerebrospinal fluid escape. AIDS. 2019;33(Suppl 2):S159–69. https://doi.org/10.1097/QAD.0000000000002266.CrossRefPubMed

48.

•• Lucas SB, Wong KT, Nightingale S, Miller RF. HIV-associated CD8 encephalitis: a UK case series and review of histopathologically confirmed cases. Front Neurol. 2021;12:628296. https://doi.org/10.3389/fneur.2021.628296. (This work illustrates the possible link between CD8 encephalitis and CSF HIV escape through the detailed work in histopathology.)CrossRefPubMedPubMedCentral

49.

•• Lustig G, Cele S, Karim F, Derache A, Ngoepe A, Khan K, et al. T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy. PLoS Pathog. 2021;17(9):e1009871. https://doi.org/10.1371/journal.ppat.1009871. (This work illustrates that latently infected T-cells remain an important source of HIV escape in CSF in addition to the viral latency in residential monocyte/macrophage in the CNS.)CrossRefPubMedPubMedCentral

50.

Joseph SB, Kincer LP, Bowman NM, Evans C, Vinikoor MJ, Lippincott CK, et al. Human immunodeficiency virus type 1 RNA detected in the central nervous system (CNS) after years of suppressive antiretroviral therapy can originate from a replicating CNS reservoir or clonally expanded cells. Clin Infect Dis. 2019;69(8):1345–52. https://doi.org/10.1093/cid/ciy1066.CrossRefPubMed

51.

Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, et al. Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS. 2017;31(1):5–14. https://doi.org/10.1097/QAD.0000000000001267.CrossRefPubMed

52.

Avalos CR, Abreu CM, Queen SE, Li M, Price S, Shirk EN, et al. Brain macrophages in simian immunodeficiency virus-infected, antiretroviral-suppressed macaques: a functional latent reservoir. MBio. 2017;8(4). https://doi.org/10.1128/mBio.01186-17

53.

Stefic K, Chaillon A, Bouvin-Pley M, Moreau A, Braibant M, Bastides F, et al. Probing the compartmentalization of HIV-1 in the central nervous system through its neutralization properties. PLoS One. 2017;12(8):e0181680. https://doi.org/10.1371/journal.pone.0181680.CrossRefPubMedPubMedCentral

54.

Hsu DC, Silsorn D, Inthawong D, Kuncharin Y, Sopanaporn J, Im-Erbsin R, et al. Impact of analytical treatment interruption on the central nervous system in a simian-HIV model. AIDS. 2019;33(Suppl 2):S189–96. https://doi.org/10.1097/QAD.0000000000002270.CrossRefPubMed

55.

Schreiber-Stainthorp W, Sinharay S, Srinivasula S, Shah S, Wang J, Dodd L, et al. Brain (18)F-FDG PET of SIV-infected macaques after treatment interruption or initiation. J Neuroinflammation. 2018;15(1):207. https://doi.org/10.1186/s12974-018-1244-z.CrossRefPubMedPubMedCentral

56.

Colby DJ, Trautmann L, Pinyakorn S, Leyre L, Pagliuzza A, Kroon E, et al. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat Med. 2018;24(7):923–6. https://doi.org/10.1038/s41591-018-0026-6.CrossRefPubMedPubMedCentral

57.

Castagna A, Muccini C, Galli L, Bigoloni A, Poli A, Spagnuolo V, et al. Analytical treatment interruption in chronic HIV-1 infection: time and magnitude of viral rebound in adults with 10 years of undetectable viral load and low HIV-DNA (APACHE study). J Antimicrob Chemother. 2019;74(7):2039–46. https://doi.org/10.1093/jac/dkz138.CrossRefPubMed

58.

Pannus P, Rutsaert S, De Wit S, Allard SD, Vanham G, Cole B, et al. Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription. J Int AIDS Soc. 2020;23(2):e25453. https://doi.org/10.1002/jia2.25453.CrossRefPubMedPubMedCentral

59.

Huiting ED, Gittens K, Justement JS, Shi V, Blazkova J, Benko E, et al. Impact of treatment interruption on HIV reservoirs and lymphocyte subsets in individuals who initiated antiretroviral therapy during the early phase of infection. J Infect Dis. 2019;220(2):270–4. https://doi.org/10.1093/infdis/jiz100.CrossRefPubMedPubMedCentral

60.

•• De Scheerder MA, Vrancken B, Dellicour S, Schlub T, Lee E, Shao W, et al. HIV rebound is predominantly fueled by genetically identical viral expansions from diverse reservoirs. Cell Host Microbe. 2019;26(3):347–58 e7. https://doi.org/10.1016/j.chom.2019.08.003. (The study outcomes indicate that a successful HIV cure possibly needs to cover a broad range of tissue reservoirs with latent HIV infection.)

61.

Andrade VM, Mavian C, Babic D, Cordeiro T, Sharkey M, Barrios L, et al. A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption. Proc Natl Acad Sci. 2020;117(18):9981–90.CrossRef

62.

Clarridge KE, Blazkova J, Einkauf K, Petrone M, Refsland EW, Justement JS, et al. Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals. PLoS Pathog. 2018;14(1):e1006792. https://doi.org/10.1371/journal.ppat.1006792.CrossRefPubMedPubMedCentral

63.

De Scheerder MA, Van Hecke C, Zetterberg H, Fuchs D, De Langhe N, Rutsaert S, et al. Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption. J Antimicrob Chemother. 2020;75(5):1311–20. https://doi.org/10.1093/jac/dkaa003.CrossRefPubMedPubMedCentral

64.

Hellmuth J, Muccini C, Colby DJ, Kroon E, de Souza M, Crowell TA, et al. Central nervous system safety during brief analytic treatment interruption of antiretroviral therapy within 4 human immunodeficiency virus remission trials: an observational study in acutely treated people living with human immunodeficiency virus. Clin Infect Dis. 2021;73(7):e1885–92. https://doi.org/10.1093/cid/ciaa1344.CrossRefPubMed

65.

Oliveira MF, Chaillon A, Nakazawa M, Vargas M, Letendre SL, Strain MC, et al. Early antiretroviral therapy is associated with lower HIV DNA molecular diversity and lower inflammation in cerebrospinal fluid but does not prevent the establishment of compartmentalized HIV DNA populations. PLoS Pathog. 2017;13(1):e1006112. https://doi.org/10.1371/journal.ppat.1006112.CrossRefPubMedPubMedCentral

66.

Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight. 2018;3(18):e121718. https://doi.org/10.1172/jci.insight.121718.

67.

McMahon JH, Zerbato JM, Lau JSY, Lange JL, Roche M, Tumpach C, et al. A clinical trial of non-invasive imaging with an anti-HIV antibody labelled with copper-64 in people living with HIV and uninfected controls. EBioMedicine. 2021;65:103252. https://doi.org/10.1016/j.ebiom.2021.103252.CrossRefPubMedPubMedCentral

68.

Vera DB, Schulte B, Henrich T, Flavell R, Seo Y, Abdelhafez Y, et al. First-in-human total-body PET imaging of HIV with 89Zr-VRC01 on the EXPLORER. J Nucl Med 2020;61(supplement 1):545.

69.

VanBrocklin H, Vera DB, Schulte B, Flavell R, Seo Y, Levi J, et al. Imaging viral load and T cell activation in HIV: tools for cure development. J Nucl Med 2020;61(supplement 1):540.

70.

Guglielmetti C, Levi J, Huynh TL, Tiret B, Blecha J, Tang R, VanBrocklin H, Chaumeil MM. Longitudinal Imaging of T Cells and Inflammatory Demyelination in a Preclinical Model of Multiple Sclerosis Using 18F-FAraG PET and MRI. J Nucl Med. 2022;63(1):140–6. https://doi.org/10.2967/jnumed.120.259325.CrossRefPubMed

Title: HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies
Authors: Phillip Chan
Serena Spudich
Publication date: 01-06-2022
Publisher: Springer US
Keywords: Human Immunodeficiency Virus
HIV-Associated Dementia
HIV-Associated Dementia
Published in: Current HIV/AIDS Reports / Issue 3/2022
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-022-00605-1

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 3/2022

HIV-1 Reservoir Persistence and Decay: Implications for Cure Strategies

COVID-19 Clinical Presentation Among HIV-Infected Persons in China: A Systematic Review

Viral and Host Biomarkers of HIV Remission Post Treatment Interruption

Interventions to Increase HIV Testing Uptake in Global Settings

Trauma-Informed HIV Care Interventions: Towards a Holistic Approach

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials