title: No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy.
abstract: BACKGROUND
  Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
  
  
  METHODS
  We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
  
  
  RESULTS
  Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
  
  
  CONCLUSIONS
  In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.
authors.affiliation: Division of Infectious Diseases and Ragon Institute, Massachusetts General Hospital, Boston, MA 02114, USA. rgandhi@partners.org
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
authors.forename: Sarah
authors.initials: S
authors.lastname: Read
authors.forename: Beatrice
authors.initials: B
authors.lastname: Kallungal
authors.forename: Ming
authors.initials: M
authors.lastname: Chang
authors.forename: Erin A
authors.initials: EA
authors.lastname: Goecker
authors.forename: Ann
authors.initials: A
authors.lastname: Wiegand
authors.forename: Mary
authors.initials: M
authors.lastname: Kearney
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Richard
authors.initials: R
authors.lastname: D'Aquila
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D000068898:Raltegravir Potassium; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014766:Viremia / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium
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