title: Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection.
abstract: BACKGROUND
  Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir.
  
  
  METHODS
  Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally.
  
  
  RESULTS
  Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4 T-cell counts was higher in the +MVC arm. Conversely, CD8 T-cell counts and CD4 T-cell activation decreased slower in the +MVC arm. Absolute CD4 T-cell and CD8 T-cell counts, immune activation, CD4/CD8 T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study.
  
  
  CONCLUSIONS
  Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR newly infected cells and recovery of CD4 T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.
authors.affiliation: aAIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona b'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona cCenter for Epidemiological Studies on STI and HIV/AIDS of Catalonia dHospital Universitari Germans Trias i Pujol, Badalona eHospital Clinic - IDIBAPS, University of Barcelona fCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. *Maria C. Puertas, Marta Massanella, and Josep M. Llibre have contributed equally to the writing of this article.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Monica
authors.initials: M
authors.lastname: Ballestero
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzon
authors.forename: Dan
authors.initials: D
authors.lastname: Ouchi
authors.forename: Anna
authors.initials: A
authors.lastname: Esteve
authors.forename: Jaume
authors.initials: J
authors.lastname: Boix
authors.forename: Christian
authors.initials: C
authors.lastname: Manzardo
authors.forename: Josep M
authors.initials: JM
authors.lastname: Miró
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003510:Cyclohexanes / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D000077592:Maraviroc; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D004279:DNA, Viral; D011760:Pyrrolidinones; D012367:RNA, Viral; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc