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J Exp Med. 2017 Nov 6;214(11):3239-3261. doi: 10.1084/jem.20162123. Epub 2017 Oct 5.

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

Author information

1
Department of Paediatrics, University of Oxford, Oxford, England, UK.
2
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
3
Oxford Martin School, University of Oxford, Oxford, England, UK.
4
Department of Zoology, University of Oxford, Oxford, England, UK.
5
Blizard Institute, Queen Mary University of London, London, England, UK.
6
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
7
Division of Medicine, Department of Paediatrics, Imperial College London, London, England, UK.
8
Medical Research Council, Durban, South Africa.
9
Witwatersrand Health Consortium, Johannesburg, South Africa.
10
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, England, UK.
11
Linacre Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, University of Witwatersrand, Johannesburg, South Africa.
12
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Nagasaki, Japan.
13
Northampton Healthcare NHS Foundation Trust, Cliftonville, England, UK.
14
Buckinghampshire Healthcare NHS Foundation Trust, High Wycombe, England, UK.
15
Paediatric Department, Kimberley Hospital, Northern Cape, South Africa.
16
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA.
17
Kymab Ltd., Babraham Research Campus, Babraham, England, UK.
18
Department of Medicine, Division of Infectious Diseases, Imperial College Faculty of Medicine, London, England, UK.
19
Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa.
20
Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, England, UK.
21
Wellcome Trust Sanger Institute, Hinxton, England, UK.
22
Department of Paediatrics, University of Oxford, Oxford, England, UK philip.goulder@paediatrics.ox.ac.uk.

Abstract

Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection.

PMID:
28983013
PMCID:
PMC5679167
DOI:
10.1084/jem.20162123
[Indexed for MEDLINE]
Free PMC Article

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