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AIDS. 2019 Mar 11. doi: 10.1097/QAD.0000000000002195. [Epub ahead of print]

HIV-1 is rarely detected in blood and colon myeloid cells during viral-suppressive antiretroviral therapy.

Author information

1
CHUM-Research Centre, Montréal, Qc, Canada.
2
Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montréal, Qc, Canada.
3
University of California Davis, Davis, CA, USA.
4
Institut de Recherche Clinique de Montréal, Montréal, Qc, Canada.
5
Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Canada.
6
Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.
7
Chronic Viral Illness Service and Research Institute, McGill University Health Centre, Montreal, QC, Canada.

Abstract

OBJECTIVE:

To explore the contribution of blood and colon myeloid cells to HIV persistence during antiretroviral therapy (ART).

DESIGN:

Leukapheresis were collected from HIV-infected individuals with undetectable plasma viral load during ART (HIV + ART; n = 15) and viremics untreated (HIV + ; n = 6). Rectal sigmoid biopsies were collected from n = 8 HIV+ART.

METHODS:

Myeloid cells (total monocytes (Mo), CD16/CD16 Mo, CD1c dendritic cells (DC)) and CD4 T-cells were isolated by MACS and/or FACS from peripheral blood. Matched myeloid and CCR6CD4 T-cells were isolated from blood and rectal biopsies by FACS. Levels of early (RU5 primers), late (Gag primers), and/or integrated HIV-DNA (Alu/HIV primers) were quantified by nested real-time PCR. Replication-competent HIV was amplified by co-culturing cells from HIV+ individuals with CD3/CD28-activated CD4 T-cells from uninfected donors.

RESULTS:

Early/late but not integrated HIV reverse transcripts were detected in blood myeloid subsets of 4/10 HIV+ART; in contrast, integrated HIV-DNA was exclusively detected in CD4 T-cells. In rectal biopsies, late HIV reverse transcripts were detected in myeloid cells and CCR6CD4 T-cells from 1/8 and 7/8 HIV+ART individuals, respectively. Replication-competent HIV was outgrown from CD4 T-cells but not from myeloid of untreated/ART-treated HIV+ individuals.

CONCLUSION:

In contrast to CD4 T-cells, blood and colon myeloid cells carry detectable HIV only in a small fraction of HIV+ART individuals. This is consistent with the documented resistance of Mo to HIV infection and the rapid turnover of Mo-derived macrophages in the colon. Future assessment of multiple lymphoid and non-lymphoid tissues is required to include/exclude myeloid cells as relevant HIV reservoirs during ART.

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