Longitudinal genetic characterization reveals that cell proliferation maintains a persistent HIV type 1 DNA pool during effective HIV therapy
S Von Stockenstrom, L Odevall, E Lee… - The Journal of …, 2015 - academic.oup.com
S Von Stockenstrom, L Odevall, E Lee, E Sinclair, P Bacchetti, M Killian, L Epling, W Shao…
The Journal of infectious diseases, 2015•academic.oup.comBackground. 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 …
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 …
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.
Oxford University Press