Format

Send to

Choose Destination
Clin Infect Dis. 2014 Nov 1;59(9):1312-21. doi: 10.1093/cid/ciu585. Epub 2014 Jul 29.

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

Author information

1
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
2
Center for Biostatistics in AIDS Research, Harvard School of Public Health.
3
Massachusetts General Hospital and Ragon Institute, Harvard Medical School, Boston.

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.

KEYWORDS:

HIV-1 persistence; antiretroviral therapy; HIV-1 DNA decay; immune activation

PMID:
25073894
PMCID:
PMC4200019
DOI:
10.1093/cid/ciu585
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center