HIV-1 is rarely detected in blood and colon myeloid cells during viral-suppressive antiretroviral therapy.
AIDS
; 33(8): 1293-1306, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-30870200
ABSTRACT
OBJECTIVE:
The aim of this study was to explore the contribution of blood and colon myeloid cells to HIV persistence during antiretroviral therapy (ART).DESIGN:
Leukapheresis was collected from HIV-infected individuals with undetectable plasma viral load during ART (HIVâ+âART; nâ=â15) and viremics untreated (HIV+; nâ=â6). Rectal sigmoid biopsies were collected from nâ=â8 HIV+ART.METHODS:
Myeloid cells (total monocytes (Mo), CD16/CD16 Mo, CD1c dendritic cells) and CD4 T cells were isolated by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (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-positive 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 four out of 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 one out of eight and seven out of eight HIV+ART individuals, respectively. Replication-competent HIV was outgrown from CD4 T cells but not from myeloid of untreated/ART-treated HIV-positive 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 nonlymphoid tissues is required to include/exclude myeloid cells as relevant HIV reservoirs during ART.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colo Sigmoide
/
Células Sanguíneas
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Infecções por HIV
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HIV-1
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Células Mieloides
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Antirretrovirais
/
Resposta Viral Sustentada
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article