title: The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients.
abstract: OBJECTIVE
  The stability of the reservoir of latently infected memory CD4 T-cells may be associated with continuous replenishment from residual HIV-1, not completely eliminated by otherwise successful antiretroviral therapy (ART). Treatment intensification could help to control residual virus and to modify the latent reservoir. The objective of this work is to assess the effect of intensifying therapy with raltegravir on the HIV-1 cell reservoir.
  
  
  METHODS
  A pilot open-label phase-II clinical trial was performed to analyze ART intensification with raltegravir after 48 weeks in chronically HIV-1-infected patients on stable ART.
  
  
  METHODS
  We measured the number of latently infected memory CD4 T cells, residual viremia, 2-long terminal repeat circles, CD4/CD8 T-cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial translocation.
  
  
  RESULTS
  A significant decay of HIV-1 latent reservoir was observed after intensification in the nine patients included (P = 0.021). No variation was found in either residual viremia or 2-long terminal repeat circles, whereas CD8 T-cell activation decreased at week 36 (P = 0.028). No differences were found in naive T-cell or effector memory cell counts, and the frequencies of gut homing receptor on activated or effector memory CD8 T cells. Bacterial translocation was stable, with the exception of a late decrease in lipopolysaccharide levels.
  
  
  CONCLUSIONS
  In this pilot noncomparative trial, treatment intensification with raltegravir significantly decreased the latent cellular HIV-1 reservoir and CD8 T-cell activation. Despite the limitations inherent to trial design, our results suggest that ART intensification should be considered as an adjuvant strategy to eradicate HIV-1 infection.
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal and IRYCIS, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vallejo
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernandez-Novoa
authors.forename: Laura
authors.initials: L
authors.lastname: Diaz
authors.forename: Nadia
authors.initials: N
authors.lastname: Madrid
authors.forename: María
authors.initials: M
authors.lastname: Abad-Fernandez
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: María J
authors.initials: MJ
authors.lastname: Perez-Elias
authors.forename: Javier
authors.initials: J
authors.lastname: Zamora
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.forename: María A
authors.initials: MA
authors.lastname: Muñoz-Fernandez
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium