title: Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.
abstract: BACKGROUND
  Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment.
  
  
  RESULTS
  In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period.
  
  
  CONCLUSIONS
  Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.
authors.affiliation: AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Zhu
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Jiao
authors.forename: Rongyue
authors.initials: R
authors.lastname: Lei
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ji
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Liu
authors.forename: Feili
authors.initials: F
authors.lastname: Wei
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Shi
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D017104:Bacteriophage M13 / Q000235:genetics; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D015345:Oligonucleotide Probes / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D015345:Oligonucleotide Probes; D019713:Receptors, CCR5