Lessons for Understanding Central Nervous System HIV Reservoirs from the Last Gift Program.
Brain
Central nervous system (CNS)
Cure
Eradication
HIV reservoirs
Spinal cord
Journal
Current HIV/AIDS reports
ISSN: 1548-3576
Titre abrégé: Curr HIV/AIDS Rep
Pays: United States
ID NLM: 101235661
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
accepted:
29
08
2022
pubmed:
20
10
2022
medline:
21
12
2022
entrez:
19
10
2022
Statut:
ppublish
Résumé
Deep tissue HIV reservoirs, especially within the central nervous system (CNS), are understudied due to the challenges of sampling brain, spinal cord, and other tissues. Understanding the cellular characteristics and viral dynamics in CNS reservoirs is critical so that HIV cure trials can address them and monitor the direct and indirect effects of interventions. The Last Gift program was developed to address these needs by enrolling altruistic people with HIV (PWH) at the end of life who agree to rapid research autopsy. Recent findings from the Last Gift emphasize significant heterogeneity across CNS reservoirs, CNS compartmentalization including differential sensitivity to broadly neutralizing antibodies, and bidirectional migration of HIV across the blood-brain barrier. Our findings add support for the potential of CNS reservoirs to be a source of rebounding viruses and reseeding of systemic sites if they are not targeted by cure strategies. This review highlights important scientific, practical, and ethical lessons learned from the Last Gift program in the context of recent advances in understanding the CNS reservoirs and key knowledge gaps in current research.
Identifiants
pubmed: 36260191
doi: 10.1007/s11904-022-00628-8
pii: 10.1007/s11904-022-00628-8
pmc: PMC9580451
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
566-579Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI164570
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI147821
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH128034
Pays : United States
Organisme : NIDA NIH HHS
ID : DP2 DA051915
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI169609
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH067127
Pays : United States
Organisme : NIDA NIH HHS
ID : DA051915
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007384
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI164567
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062512
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA055491
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH118120
Pays : United States
Organisme : NIDA NIH HHS
ID : DA055491
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131385
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Curr Opin HIV AIDS. 2020 Mar;15(2):142-149
pubmed: 31895141
Med Care. 2018 Oct;56 Suppl 10 Suppl 1:S6-S8
pubmed: 30015725
Clin Infect Dis. 2022 Oct 12;75(8):1342-1350
pubmed: 35234862
J Clin Invest. 2020 Apr 1;130(4):1611-1614
pubmed: 32091411
AIDS Res Hum Retroviruses. 2020 Dec;36(12):1033-1046
pubmed: 32449624
J Neurochem. 2018 Dec;147(6):784-802
pubmed: 30152135
Nat Med. 2020 Sep;26(9):1339-1350
pubmed: 32895573
Top Antivir Med. 2011 Nov;19(4):137-42
pubmed: 22156215
J Clin Invest. 2020 Jul 1;130(7):3381-3390
pubmed: 32609095
AIDS. 2019 Dec 1;33 Suppl 2:S107-S111
pubmed: 31790376
Cell Host Microbe. 2017 Apr 12;21(4):494-506.e4
pubmed: 28407485
Clin Infect Dis. 2019 Aug 30;69(6):1063-1067
pubmed: 30715211
PLoS One. 2015 Oct 02;10(10):e0139510
pubmed: 26431315
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11341-E11348
pubmed: 30420517
Sci Transl Med. 2019 Oct 9;11(513):
pubmed: 31597754
AIDS. 2020 Jun 1;34(7):1089-1092
pubmed: 32287073
AIDS. 2019 Nov 15;33(14):2157-2166
pubmed: 31688040
AIDS. 2019 Dec 1;33 Suppl 2:S181-S188
pubmed: 31789817
J Neurovirol. 2015 Jun;21(3):276-89
pubmed: 25236812
Front Immunol. 2016 Jan 28;7:12
pubmed: 26858716
N Engl J Med. 2009 Feb 12;360(7):692-8
pubmed: 19213682
Biomol Detect Quantif. 2015 Aug 21;5:3-9
pubmed: 27077037
Mol Psychiatry. 2020 Feb;25(2):351-367
pubmed: 31772305
J Med Virol. 2016 Apr;88(4):606-13
pubmed: 26348372
J Infect Dis. 2017 Dec 27;217(1):69-81
pubmed: 29069436
Nature. 2002 Jan 17;415(6869):331-5
pubmed: 11797011
AJSP Rev Rep. 2021 Mar-Apr;26(2):100-107
pubmed: 33718610
AIDS Res Hum Retroviruses. 2020 Dec;36(12):1071-1082
pubmed: 32449625
J Clin Invest. 2019 Jul 15;129(8):3339-3346
pubmed: 31305262
Br J Cancer. 2021 Sep;125(7):920-926
pubmed: 34112947
Lancet Microbe. 2021 May;2(5):e198-e209
pubmed: 35544209
J Virol. 2010 Mar;84(6):2913-22
pubmed: 20032180
Cell Rep. 2017 Oct 17;21(3):813-822
pubmed: 29045846
BMC Public Health. 2011 Oct 11;11:791
pubmed: 21988839
PLoS One. 2018 Jul 23;13(7):e0199670
pubmed: 30036365
J Virol. 2020 Jan 17;94(3):
pubmed: 31694954
J Virol. 2016 May 27;90(12):5643-5656
pubmed: 27030272
PLoS One. 2010 May 07;5(5):e10523
pubmed: 20479889
PLoS Comput Biol. 2015 Oct 16;11(10):e1004292
pubmed: 26474290
Antimicrob Agents Chemother. 2019 Dec 20;64(1):
pubmed: 31611355
Nature. 2021 May;593(7860):506-509
pubmed: 34035530
J Am Geriatr Soc. 2021 Mar;69(3):678-687
pubmed: 33155270
Neurology. 2000 Feb 22;54(4):927-36
pubmed: 10690988
PLoS One. 2017 Apr 6;12(4):e0175123
pubmed: 28384249
J Virus Erad. 2020 Aug 25;6(4):100008
pubmed: 33294210
Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Dec;5(4):213-9
pubmed: 15799549
J Mol Diagn. 2017 Mar;19(2):236-243
pubmed: 28012713
PLoS One. 2021 May 13;16(5):e0250987
pubmed: 33983973
AIDS. 2017 Jan 2;31(1):1-4
pubmed: 27755112
Nat Rev Microbiol. 2016 Jan;14(1):55-60
pubmed: 26616417
Neurology. 2013 Jan 8;80(2):196-202
pubmed: 23269596
Int J Legal Med. 2011 Jul;125(4):573-80
pubmed: 21584656
Nat Commun. 2019 Feb 13;10(1):728
pubmed: 30760706
Clin Infect Dis. 2019 Aug 30;69(6):1068-1070
pubmed: 30715193
Clin Infect Dis. 2019 Sep 27;69(8):1345-1352
pubmed: 30561541
J Gen Intern Med. 2019 Jun;34(6):839-845
pubmed: 30859504
Future Virol. 2020 Jul;15(7):397-400
pubmed: 32868981
J Clin Pathol. 2019 Oct;72(10):689-695
pubmed: 31262953
BMC Med Ethics. 2022 Jan 11;23(1):2
pubmed: 35012544
Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25891-25899
pubmed: 31776247
J Neurovirol. 2019 Dec;25(6):741-753
pubmed: 31144289
Curr Top Behav Neurosci. 2021;50:77-103
pubmed: 31385260
Viruses. 2019 Feb 27;11(3):
pubmed: 30818749
BMC Med Ethics. 2018 Oct 20;19(1):83
pubmed: 30342507
J Leukoc Biol. 2018 Mar;103(3):421-431
pubmed: 29389021
Neuropathol Appl Neurobiol. 2001 Aug;27(4):326-35
pubmed: 11532163
J Neuropathol Exp Neurol. 2015 Jan;74(1):38-47
pubmed: 25470348
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1883-8
pubmed: 26858442
AIDS. 2020 Sep 1;34(11):1609-1614
pubmed: 32701585
J Neurovirol. 2019 Oct;25(5):622-633
pubmed: 30790184
AIDS Res Hum Retroviruses. 2017 Nov;33(11):1155-1165
pubmed: 28486838
Lancet HIV. 2020 May;7(5):e340-e347
pubmed: 32169158
Nat Commun. 2019 Jul 19;10(1):3193
pubmed: 31324762
AIDS. 2019 Dec 1;33 Suppl 2:S123-S133
pubmed: 31090545
J Virol. 2020 Dec 9;:
pubmed: 33298546
Mol Neurobiol. 2020 Feb;57(2):1115-1130
pubmed: 31691183
PLoS Pathog. 2015 Mar 26;11(3):e1004720
pubmed: 25811757
Nat Med. 2017 May;23(5):638-643
pubmed: 28414330
Sci Rep. 2017 Jan 13;7:40508
pubmed: 28084418
J Immunol Res. 2021 Sep 29;2021:7316456
pubmed: 34631899
Virus Evol. 2016 Aug 03;2(2):vew020
pubmed: 27774305
Front Immunol. 2021 May 27;12:688747
pubmed: 34122453
Immunity. 2018 May 15;48(5):872-895
pubmed: 29768175
J Clin Epidemiol. 2018 Oct;102:12-22
pubmed: 29859242
Pathogens. 2021 Aug 12;10(8):
pubmed: 34451482
Cell Host Microbe. 2019 Sep 11;26(3):347-358.e7
pubmed: 31471273
Cell Rep. 2021 Aug 31;36(9):109643
pubmed: 34469719
J Infect Dis. 2011 Mar 15;203(6):765-72
pubmed: 21343146
AIDS Res Treat. 2012;2012:186850
pubmed: 22461978
Nat Commun. 2019 Jan 22;10(1):380
pubmed: 30670690
Neurology. 2010 Dec 7;75(23):2087-96
pubmed: 21135382
AIDS. 2017 Apr 24;31(7):1051-1052
pubmed: 28350582
J Neuroimmune Pharmacol. 2021 Mar;16(1):90-112
pubmed: 31385157
ACS Chem Neurosci. 2015 Aug 19;6(8):1276-89
pubmed: 26034832
J Virol. 2015 Nov 18;90(3):1369-76
pubmed: 26581989
PLoS One. 2020 Nov 18;15(11):e0242420
pubmed: 33206710
PLoS Pathog. 2017 Jan 3;13(1):e1006112
pubmed: 28046096
Eur J Cancer. 2018 Nov;103:120-126
pubmed: 30223225
Curr Top Behav Neurosci. 2021;50:517-545
pubmed: 33604875
Curr HIV/AIDS Rep. 2019 Apr;16(2):129-140
pubmed: 30835045
J Neuroimmune Pharmacol. 2021 Mar;16(1):130-143
pubmed: 31823251
Mol Biol Evol. 2015 Jan;32(1):268-74
pubmed: 25371430
PLoS Pathog. 2021 Sep 23;17(9):e1009871
pubmed: 34555123
J Infect Dis. 2012 Jul 15;206(2):275-82
pubmed: 22551810
Curr HIV Res. 2016;14(5):373-381
pubmed: 27719663
AIDS. 2018 Sep 10;32(14):2005-2015
pubmed: 29912063
Nat Biotechnol. 2016 Oct;34(10):1010-1014
pubmed: 27617737
J Clin Invest. 2016 Apr 1;126(4):1353-66
pubmed: 26950420
Nature. 2019 Feb;566(7742):120-125
pubmed: 30700913
Gerontologist. 2002 Oct;42 Spec No 3:86-98
pubmed: 12415138
Science. 2014 Aug 1;345(6196):570-3
pubmed: 25011556
Nature. 2021 Jul;595(7867):352
pubmed: 34257439
J Neurovirol. 2022 Feb;28(1):64-91
pubmed: 35138593
Cell Rep. 2020 Feb 4;30(5):1271-1281
pubmed: 32023447
J Int AIDS Soc. 2016 Feb 18;19(1):20706
pubmed: 26900031
Front Microbiol. 2019 Oct 01;10:2204
pubmed: 31632364
Front Microbiol. 2021 Apr 07;12:646447
pubmed: 33897659
PLoS Pathog. 2011 Oct;7(10):e1002286
pubmed: 22007152
J Vis Exp. 2021 May 6;(171):
pubmed: 34028448
Neuroscience. 1992;48(2):405-15
pubmed: 1603325
Int J Mol Sci. 2019 Jun 28;20(13):
pubmed: 31261683
Xenobiotica. 2019 Oct;49(10):1192-1201
pubmed: 30346892
J Acquir Immune Defic Syndr. 2019 Jan 1;80(1):15-23
pubmed: 30365450
J Neurosci. 2017 Mar 29;37(13):3599-3609
pubmed: 28270571
J Virus Erad. 2015 Jan 01;1(1):17-22
pubmed: 27482392
Clin Infect Dis. 2019 Jan 18;68(3):490-497
pubmed: 30107467
J Clin Invest. 2020 Apr 1;130(4):1699-1712
pubmed: 31910162
J Neurooncol. 2019 Nov;145(2):349-355
pubmed: 31571114
mBio. 2017 Aug 15;8(4):
pubmed: 28811349
PLoS One. 2021 May 7;16(5):e0250882
pubmed: 33961653
Acta Neuropathol Commun. 2020 Jun 26;8(1):92
pubmed: 32586411
Database (Oxford). 2019 Jan 1;2019:
pubmed: 30624650