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

TitleLevels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation.
Publication TypeJournal Article
Year of Publication2017
AuthorsGandhi RT, McMahon DK, Bosch RJ, Lalama CM, Cyktor JC, Macatangay BJ, Rinaldo CR, Riddler SA, Hogg E, Godfrey C, Collier AC, Eron JJ, Mellors JW
Corporate AuthorsACTG A5321 Team
JournalPLoS Pathog
Volume13
Issue4
Paginatione1006285
Date Published2017 Apr
ISSN1553-7374
KeywordsAdult, Anti-HIV Agents, Anti-Retroviral Agents, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV Infections, HIV-1, Humans, Inflammation, Lymphocyte Activation, Male, Viremia
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.

DOI10.1371/journal.ppat.1006285
Alternate JournalPLoS Pathog.
PubMed ID28426825
PubMed Central IDPMC5398724
Grant ListUM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States