A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation.
Adult
Argentina
CD4-Positive T-Lymphocytes
/ immunology
Female
Genotype
HIV Infections
/ genetics
HIV-1
/ genetics
High-Throughput Nucleotide Sequencing
Host-Pathogen Interactions
Humans
Massachusetts
Pregnancy
Pregnancy Outcome
Proviruses
/ genetics
Receptors, CCR5
/ genetics
Viral Load
Viremia
/ virology
Virus Replication
/ immunology
Journal
Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
pubmed:
17
11
2021
medline:
15
2
2022
entrez:
16
11
2021
Statut:
ppublish
Résumé
A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. Detailed investigation of virologic and immunologic characteristics. Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4 Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. National Institutes of Health and Bill & Melinda Gates Foundation.
Sections du résumé
BACKGROUND
A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection.
OBJECTIVE
To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy.
DESIGN
Detailed investigation of virologic and immunologic characteristics.
SETTING
Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts.
PATIENT
A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication.
MEASUREMENTS
Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing.
RESULTS
No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4
LIMITATIONS
Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved.
CONCLUSION
Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection.
PRIMARY FUNDING SOURCE
National Institutes of Health and Bill & Melinda Gates Foundation.
Identifiants
pubmed: 34781719
doi: 10.7326/L21-0297
pmc: PMC9215120
mid: NIHMS1811201
doi:
Substances chimiques
CCR5 protein, human
0
Receptors, CCR5
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-100Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI126620
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI078799
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI155233
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134539
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI114235
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI152979
Pays : United States
Organisme : NIDA NIH HHS
ID : R61 DA047034
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130005
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI116228
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150396
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI116228
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI135940
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI155171
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI117841
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120387
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120008
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126611
Pays : United States
Commentaires et corrections
Type : CommentIn
Références
Front Immunol. 2021 Mar 19;12:650028
pubmed: 33815410
J Vis Exp. 2015 May 21;(99):e52863
pubmed: 26067211
Methods Mol Biol. 2016;1354:239-53
pubmed: 26714716
PLoS Pathog. 2013;9(5):e1003347
pubmed: 23671416
Cell. 2013 Oct 24;155(3):519-29
pubmed: 24243012
PLoS Pathog. 2013 Mar;9(3):e1003211
pubmed: 23516360
J Clin Invest. 2019 Mar 1;129(3):988-998
pubmed: 30688658
Nature. 2019 Apr;568(7751):244-248
pubmed: 30836379
Nature. 2020 Sep;585(7824):261-267
pubmed: 32848246
J Virol. 2007 Mar;81(5):2508-18
pubmed: 17151109
Nature. 2005 Jan 27;433(7024):430-3
pubmed: 15674295
N Engl J Med. 2009 Feb 12;360(7):692-8
pubmed: 19213682
Front Immunol. 2018 Oct 23;9:2443
pubmed: 30405632
J Immunol Methods. 1992 Feb 5;146(2):185-93
pubmed: 1538142
J Clin Invest. 2017 Jun 30;127(7):2689-2696
pubmed: 28628034
N Engl J Med. 1995 Jan 26;332(4):228-32
pubmed: 7808489
Open Forum Infect Dis. 2020 Apr 02;7(5):ofaa115
pubmed: 32391403