title: The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial.
abstract: BACKGROUND
  Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered the level of residual viremia in such patients.
  
  
  RESULTS
  Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART. The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 (10/12) compared between treatment groups. Fifty-three patients were enrolled. The median screening HIV-1 RNA was 1.7 copies/mL. The HIV-1 RNA level at weeks 10/12 did not differ significantly between the raltegravir-intensified (n = 25) and the placebo (n = 24) groups (median 1.2 versus 1.7 copies/mL, p = 0.55, Wilcoxon rank sum test), nor did the change in HIV-1 RNA level from baseline to week 10/12 (median -0.2 and -0.1 copies/mL, p = 0.71, Wilcoxon rank sum test). There was also no significant change in HIV-1 RNA level from weeks 10/12 to weeks 22/24 after patients crossed-over. There was a greater CD4 cell count increase from baseline to week 12 in the raltegravir-intensified group compared with the placebo group (+42 versus -44 cells/mm(3), p = 0.082, Wilcoxon rank sum test), which reversed after the cross-over. This CD4 cell count change was not associated with an effect of raltegravir intensification on markers of CD4 or CD8 cell activation in blood.
  
  
  CONCLUSIONS
  In this randomized, double-blind cross-over study, 12 weeks of raltegravir intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended ART. This finding suggests that residual viremia does not arise from ongoing cycles of HIV-1 replication and infection of new cells. New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00515827
authors: Massachusetts General Hospital and Ragon Institute, Boston, Massachusetts, United States of America. rgandhi@partners.org
authors: Rajesh T
authors: RT
authors: Gandhi
authors: Lu
authors: L
authors: Zheng
authors: Ronald J
authors: RJ
authors: Bosch
authors: Ellen S
authors: ES
authors: Chan
authors: David M
authors: DM
authors: Margolis
authors: Sarah
authors: S
authors: Read
authors: Beatrice
authors: B
authors: Kallungal
authors: Sarah
authors: S
authors: Palmer
authors: Kathy
authors: K
authors: Medvik
authors: Michael M
authors: MM
authors: Lederman
authors: Nadia
authors: N
authors: Alatrakchi
authors: Jeffrey M
authors: JM
authors: Jacobson
authors: Ann
authors: A
authors: Wiegand
authors: Mary
authors: M
authors: Kearney
authors: John M
authors: JM
authors: Coffin
authors: John W
authors: JW
authors: Mellors
authors: Joseph J
authors: JJ
authors: Eron
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019562:Viral Load / Q000379:methods; D014766:Viremia / Q000097:blood / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium