title: Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study.
abstract: BACKGROUND
  Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation.
  
  
  METHODS
  This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks.
  
  
  RESULTS
  Total and integrated HIV-1 DNA, and ultrasensitive VL remained stable despite intensification. There was a significant increase in episomal HIV DNA at weeks 2-4 in the raltegravir group returning to baseline levels at week 48. Median CD4(+) T-cell counts increased 124 and 80 cells/µl in the intensified and control groups after 48 weeks (P=0.005 and P=0.027, respectively), without significant differences between groups. No major changes were observed in activation of CD4(+) T-cells. Conversely, raltegravir intensification significantly reduced activation of CD8(+) T-cells at week 48 (HLA-DR(+)CD38(+), P=0.005), especially in the memory compartment (CD38(+) of CD8(+)CD45RO(+), P<0.0001). Linear mix models also depicted a larger decrease in CD8(+) T-cell activation in the intensification group (P=0.036 and P=0.010, respectively). Raltegravir intensification was not associated to any particular adverse event.
  
  
  CONCLUSIONS
  Intensification of HAART with raltegravir during 48 weeks was safe and associated with a significant decrease in CD8(+) T-cell activation, and a transient increase of episomal HIV-1 DNA. However, raltegravir did not significantly contribute to changes in CD4(+) T-cell counts, ultrasensitive VL, and total and integrated HIV-1 DNA. These findings suggest that raltegravir impacts residual HIV-1 replication and support new strategies to impair HIV-1 persistence. ClinicalTrials.gov identifier: NCT00554398.
authors.affiliation: Lluita contra la SIDA Foundation, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. jmllibre.fls.germanstrias@gencat.cat
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Anna
authors.initials: A
authors.lastname: Esteve
authors.forename: Viktor
authors.initials: V
authors.lastname: Dahl
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Maria
authors.initials: M
authors.lastname: Larrouse
authors.forename: Mar
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium