title: Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected.
abstract: OBJECTIVE
  The primary objective was to assess the effect of MVC intensification on latently infected CD4(+) T cells in chronically HIV-1-infected patients receiving antiretroviral therapy.
  
  
  METHODS
  We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation.
  
  
  RESULTS
  Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4(+) or CD8(+) counts, although a significant decrease was found in the proportion of HLA-DR(+)/CD38(+) CD4(+) and CD8(+) T-cells. LPS and sCD14 levels increased.
  
  
  CONCLUSIONS
  Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00795444.
authors.affiliation: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, and IRYCIS, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Laura
authors.initials: L
authors.lastname: Díaz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vallejo
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernández-Novoa
authors.forename: María
authors.initials: M
authors.lastname: Abad
authors.forename: Nadia
authors.initials: N
authors.lastname: Madrid
authors.forename: Viktor
authors.initials: V
authors.lastname: Dahl
authors.forename: Rafael
authors.initials: R
authors.lastname: Rubio
authors.forename: Ana M
authors.initials: AM
authors.lastname: Moreno
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: José Luis
authors.initials: JL
authors.lastname: Casado
authors.forename: Enrique
authors.initials: E
authors.lastname: Navas
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: Javier
authors.initials: J
authors.lastname: Zamora
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D065100:CCR5 Receptor Antagonists; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D004270:DNA, Circular / Q000235:genetics; D004197:Disease Reservoirs / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D004270:DNA, Circular; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc