title: Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial.
abstract: BACKGROUND
  Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs despite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus Raltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells during a randomized trial.
  
  
  METHODS
  We randomly assigned for 48 weeks 22 patients to continue their current first line regimen of Truvada® plus Kaletra® or intensify it with Maraviroc and Raltegravir. The primary objective was to obtain a 50% decrease in proviral HIV-1 DNA levels in lymphoid cells with intensification. Blood samples were drawn at W-2, W0, W2, W4, W12, W24 and W48. Plasma viremia, cellular proviral DNA and cellular RNA, 2-LTR circles and lymphocytes subsets were assayed using validated methods. Patients in the intensified group underwent a gut biopsy at baseline and W48 to measure proviral DNA levels. Statistical analysis used parametric and non-parametric tests.
  
  
  RESULTS
  Ten patients in each arm completed the trial. The 2 populations were comparable at baseline. No change in the reservoir size was observed in the intensified arm compared to the control arm measured in peripheral blood mononuclear cells (PBMCs). No change in the reservoir size was observed in gut proviral DNA in the intensified arm. In this group, no increase in 2-LTR circles was observed as early as 2 weeks after intensification and no change was found in residual plasma RNA levels measured by the single copy assay. However, a decrease in CD8(+) T cells activation was observed at 24 and 48 weeks, as well as in PBMCs HIV-1 RNA levels.
  
  
  CONCLUSIONS
  We conclude that the intensification of a Protease Inhibitor regimen with Maraviroc and Raltegravir does not impact the blood proviral DNA reservoir of HIV but can decrease the cell-associated HIV RNA, the CD8 activation and has a possible impact on rectal proviral HIV DNA in some patients.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier number NCT00935480.
authors.affiliation: Department of Infectious Diseases, Sainte Musse, General Hospital, 54 rue Henri Sainte Claire Deville, 83100 Toulon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lafeuillade
authors.affiliation: Department of Infectious Diseases, Sainte Musse, General Hospital, 54 rue Henri Sainte Claire Deville, 83100 Toulon, France.
authors.forename: Assi
authors.initials: A
authors.lastname: Assi
authors.affiliation: Department of Virology, General Hospital, Toulon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Poggi
authors.affiliation: Department of Immunology, General Hospital, Toulon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bresson-Cuquemelle
authors.affiliation: Department of Biology, General Hospital, Toulon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jullian
authors.affiliation: Department of Virology, University Hospital, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
keywords: HIV DNA; HIV intensification; HIV remission; HIV reservoirs; Maraviroc; Raltegravir; cART Intensification