Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir During Suppressive Antiretroviral Therapy.
Adult
Anti-Retroviral Agents
/ therapeutic use
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Cross-Sectional Studies
Estrogen Receptor alpha
/ genetics
Female
Gene Expression
HIV Infections
/ drug therapy
HIV-1
/ genetics
Humans
Leukocytes, Mononuclear
Male
Middle Aged
Sex Factors
Virus Latency
HIV
cure
men
reservoir
women
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
09 11 2020
09 11 2020
Historique:
received:
18
03
2020
accepted:
27
05
2020
pubmed:
5
6
2020
medline:
26
3
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men. ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells. We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes. Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.
Sections du résumé
BACKGROUND
Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men.
METHODS
ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells.
RESULTS
We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes.
CONCLUSIONS
Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.
Identifiants
pubmed: 32496542
pii: 5851386
doi: 10.1093/infdis/jiaa298
pmc: PMC7653086
doi:
Substances chimiques
Anti-Retroviral Agents
0
Estrogen Receptor alpha
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1843-1852Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL146333
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002489
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134363
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146242
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146193
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000004
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146194
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050410
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI145588
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126619
Pays : United States
Organisme : NIAID NIH HHS
ID : L30 AI057417
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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