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J Infect Dis. 2015 Aug 15;212(4):596-607. doi: 10.1093/infdis/jiv092. Epub 2015 Feb 23.

Longitudinal Genetic Characterization Reveals That Cell Proliferation Maintains a Persistent HIV Type 1 DNA Pool During Effective HIV Therapy.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
3
Westmead Millennium Institute for Medical Research University of Sydney, Westmead, Australia.
4
Department of Medicine.
5
Department of Epidemiology and Biostatistics, University of California-San Francisco.
6
Leidos Biomedical Research, INC, Frederick National Laboratory for Cancer Research.
7
Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Belgium.
8
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
9
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Westmead Millennium Institute for Medical Research University of Sydney, Westmead, Australia.

Abstract

BACKGROUND:

The stability of the human immunodeficiency virus type 1 (HIV-1) reservoir and the contribution of cellular proliferation to the maintenance of the reservoir during treatment are uncertain. Therefore, we conducted a longitudinal analysis of HIV-1 in T-cell subsets in different tissue compartments from subjects receiving effective antiretroviral therapy (ART).

METHODS:

Using single-proviral sequencing, we isolated intracellular HIV-1 genomes derived from defined subsets of CD4(+) T cells from peripheral blood, gut-associated lymphoid tissue and lymph node tissue specimens from 8 subjects with virologic suppression during long-term ART at 2 time points (time points 1 and 2) separated by 7-9 months.

RESULTS:

DNA integrant frequencies were stable over time (<4-fold difference) and highest in memory T cells. Phylogenetic analyses showed that subjects treated during chronic infection contained viral populations with up to 73% identical sequence expansions, only 3 of which were observed in specimens obtained before therapy. At time points 1 and 2, such clonally expanded populations were found predominantly in effector memory T cells from peripheral blood and lymph node tissue specimens.

CONCLUSIONS:

Memory T cells maintained a relatively constant HIV-1 DNA integrant pool that was genetically stable during long-term effective ART. These integrants appear to be maintained by cellular proliferation and longevity of infected cells, rather than by ongoing viral replication.

KEYWORDS:

HIV-1 persistence; HIV-1 reservoir; memory T cells

PMID:
25712966
PMCID:
PMC4539896
DOI:
10.1093/infdis/jiv092
[Indexed for MEDLINE]
Free PMC Article

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