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Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2021 Feb 03; Vol. 223 (2), pp. 225-233. - Publication Year :
- 2021
-
Abstract
- Background: HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well defined in people on ART.<br />Methods: We separately quantified intact and defective proviruses, residual plasma viremia, and markers of inflammation and activation in people on long-term ART.<br />Results: Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life, 7.1 years; 95% confidence interval [CI], 3.9-18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6-75). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART time point to about 5% at the last. Intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation.<br />Conclusions: Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion.<br /> (© 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.)
- Subjects :
- Adult
Anti-HIV Agents therapeutic use
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
DNA, Viral
Female
HIV Infections drug therapy
HIV Infections immunology
HIV-1 immunology
Humans
Male
Middle Aged
RNA, Viral
Time Factors
Anti-HIV Agents pharmacology
HIV Infections virology
HIV-1 genetics
Proviruses drug effects
Proviruses genetics
Viral Load
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 223
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 32823274
- Full Text :
- https://doi.org/10.1093/infdis/jiaa532