Format

Send to

Choose Destination
PLoS Pathog. 2017 Apr 20;13(4):e1006285. doi: 10.1371/journal.ppat.1006285. eCollection 2017 Apr.

Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation.

Author information

1
Department of Infectious Diseases, Massachusetts General Hospital and Ragon Institute, Boston, Massachusetts, United States of America.
2
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
3
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
4
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
5
Social & Scientific Systems, Inc., Silver Spring, Maryland, United States of America.
6
Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
7
Department of Medicine, University of Washington, Seattle, Washington, United States of America.
8
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Abstract

Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525-fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA-RNA before starting treatment had higher levels while on ART, despite suppression of plasma viremia for many years. Markers of inflammation and T cell activation were associated with plasma HIV-1 RNA levels before ART was initiated but there were no consistent associations between these markers and HIV-1 DNA or CA-RNA during long-term ART, suggesting that HIV-1 persistence is not driving or driven by inflammation or activation. Higher levels of inflammation, T cell activation and cycling before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression. These findings should stimulate studies of viral and host factors that affect virologic, inflammatory and immunologic set points prior to ART initiation and should inform the design of strategies to reduce HIV-1 reservoirs and dampen immune activation that persists despite ART.

PMID:
28426825
PMCID:
PMC5398724
DOI:
10.1371/journal.ppat.1006285
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center