title: Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy.
abstract: OBJECTIVE
  To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut.
  
  
  METHODS
  Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml.
  
  
  METHODS
  Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers.
  
  
  RESULTS
  Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum.
  
  
  CONCLUSIONS
  Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.
authors.affiliation: San Francisco VA Medical Center (SFVAMC) and University of California, San Francisco (UCSF), San Francisco, California, USA. steven.yukl@ucsf.edu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Yukl
authors.forename: Amandeep K
authors.initials: AK
authors.lastname: Shergill
authors.forename: Kenneth
authors.initials: K
authors.lastname: McQuaid
authors.forename: Sara
authors.initials: S
authors.lastname: Gianella
authors.forename: Harry
authors.initials: H
authors.lastname: Lampiris
authors.forename: C Bradley
authors.initials: CB
authors.lastname: Hare
authors.forename: Mark
authors.initials: M
authors.lastname: Pandori
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000276:immunology*; D000068898:Raltegravir Potassium; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium
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