HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy.

TitleHIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2014
AuthorsBesson GJ, Lalama CM, Bosch RJ, Gandhi RT, Bedison MA, Aga E, Riddler SA, McMahon DK, Hong F, Mellors JW
JournalClin Infect Dis
Volume59
Issue9
Pagination1312-21
Date Published2014 Nov 1
ISSN1537-6591
KeywordsAdult, Anti-Retroviral Agents, CD4 Lymphocyte Count, DNA, Viral, Female, HIV Infections, HIV-1, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Viral Load, Viremia, Young Adult
Abstract

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) DNA dynamics during long-term antiretroviral therapy (ART) are not defined.

METHODS: Blood mononuclear cells obtained during 7-12 years of effective ART were assayed for total HIV-1 DNA and 2-long terminal repeat (LTR) circles by quantitative polymerase chain reaction (qPCR). Slopes of HIV-1 DNA were estimated by participant-specific linear regressions. Plasma was assayed for residual viremia (HIV-1 RNA) by qPCR.

RESULTS: Thirty participants were studied. HIV-1 DNA decreased significantly from years 0-1 and 1-4 of ART with median decay slopes of -0.86 (interquartile range, -1.05, -0.59) and -0.11 (-0.17, -0.06) log10(copies/10(6) CD4+ T-cells)/year, respectively (P < .001). Decay was not significant for years 4-7 (-0.02 [-0.06, 0.02]; P = .09) or after year 7 of ART (-0.006 [-0.030, 0.015]; P = .17). All participants had detectable HIV-1 DNA after 10 years (median 439 copies/10(6) CD4+ T-cells; range: 7-2074). Pre-ART HIV-1 DNA levels were positively associated with pre-ART HIV-1 RNA levels (Spearman = 0.71, P < .001) and with HIV-1 DNA at years 4, 7, and 10 on ART (Spearman ≥ 0.75, P < .001). No associations were found (P ≥ .25) between HIV-1 DNA slopes or levels and % activated CD8+ T-cells (average during years 1-4) or residual viremia (n = 18). 2-LTR circles were detected pre-ART in 20/29 and in 8/30 participants at last follow-up.

CONCLUSIONS: Decay of HIV-1 DNA in blood is rapid in the first year after ART initiation (86% decline), slows during years 1-4 (23% decline/year), and subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+ T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA persistence require further elucidation. Clinical Trials Registration. NCT00001137.

DOI10.1093/cid/ciu585
Alternate JournalClin. Infect. Dis.
PubMed ID25073894
PubMed Central IDPMC4200019
Grant ListAAI38855 / / PHS HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069494 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States