title: HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy.
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.
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Guillaume J
authors: GJ
authors: Besson
authors: Center for Biostatistics in AIDS Research, Harvard School of Public Health.
authors: Christina M
authors: CM
authors: Lalama
authors: Center for Biostatistics in AIDS Research, Harvard School of Public Health.
authors: Ronald J
authors: RJ
authors: Bosch
authors: Massachusetts General Hospital and Ragon Institute, Harvard Medical School, Boston.
authors: Rajesh T
authors: RT
authors: Gandhi
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Margaret A
authors: MA
authors: Bedison
authors: Center for Biostatistics in AIDS Research, Harvard School of Public Health.
authors: Evgenia
authors: E
authors: Aga
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Sharon A
authors: SA
authors: Riddler
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Deborah K
authors: DK
authors: McMahon
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Feiyu
authors: F
authors: Hong
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: John W
authors: JW
authors: Mellors
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014766:Viremia / Q000821:virology; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral
keywords: HIV-1 persistence; antiretroviral therapy; HIV-1 DNA decay; immune activation