title: Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy:  a randomized controlled trial.
abstract: BACKGROUND
  Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART.
  
  
  OBJECTIVE
  We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut).
  
  
  METHODS
  Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400  mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4(+) T cells carrying HIV-1 proviral DNA was determined.
  
  
  RESULTS
  Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4(+) T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4(+) T-cell counts.
  
  
  CONCLUSIONS
  In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4(+) T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4(+) T-cell counts.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chege
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Charles
authors.initials: C
authors.lastname: la Porte
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.forename: Desheng
authors.initials: D
authors.lastname: Su
authors.forename: Gabor
authors.initials: G
authors.lastname: Kandel
authors.forename: Jason
authors.initials: J
authors.lastname: Brunetta
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Prameet M
authors.initials: PM
authors.lastname: Sheth
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Mona R
authors.initials: MR
authors.lastname: Loutfy
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011533:Proviruses / Q000187:drug effects* / Q000235:genetics; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium