Pilot Study on the Effect of Adding Raltegravir +/- a Second Drug on HIV Levels in the Gut
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional

Summary: 
      The "PLUS" study is a pilot study to measure the effect of therapy intensification (with
      raltegravir and optional second agent) on HIV levels in the gut and blood in patients on
      antiretroviral therapy (ART) with viral load < 50 copies/mL (herein referred to as
      "suppressed"). We hypothesize that there is ongoing replication in the gut despite
      suppressive ART and that this replication can be inhibited by the addition of one or two new
      antiretroviral drugs whose activity affects a distinct part of the viral life cycle. All
      study participants will have upper and lower endoscopy at baseline (before intensification)
      and after intensification. These endoscopies will be used to obtain gut tissue and single
      cells (for CD4+ cells) .
    

Detailed description: 
      The "PLUS" study is a prospective, longitudinal pilot study to measure the effect of therapy
      intensification (with raltegravir and possible addition of a study PI or NNRTI-Non-Nucleoside
      Reverse Transcriptase Inhibitor) on HIV-1 DNA/RNA levels in the gut-associated lymphoid
      tissue (GALT) and blood in patients on ART with viral load (VL) < 50 copies/mL (herein
      referred to as "suppressed"). We hypothesize that there is ongoing replication in the GALT
      despite suppressive ART and that this replication can be inhibited by the addition of one or
      two new antiretroviral drugs whose activity affects a distinct part of the viral life cycle.
      All study participants will have a colonoscopy and esophagogastroduodenoscopy (EGD) at
      baseline (before intensification) and a second colonoscopy with EGD 12 weeks after
      intensification. These endoscopies will be used to obtain GALT mononuclear cells (for CD4+
      lymphocytes) as well as tissue for in situ hybridization and immunohistochemical studies.
    

Intervention name(s): raltegravir; Study NNRTI; Study PI
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The baseline ART regimen will be intensified with raltegravir 400mg orally (PO) twice daily (BID) (all participants) +/- a study NNRTI or protease inhibitor (PI) (at the option of the participant and the study clinical team).; Subjects who are not already on an NNRTI and who are suitable candidates will have the option of adding a study NNRTI (either efavirenz or etravirine).; Subjects who are not on a PI and who are suitable candidates will have the option of adding a study PI. PIs used as study drugs will include atazanavir (+/- ritonavir), fosamprenavir (+/-ritonavir), lopinavir/ritonavir, and darunavir/ritonavir.
Other intervention name(s): Isentress; efavirenz (Sustiva); etravirine (Intelence; atazanavir (Reyataz, ATV); fosamprenavir (Lexiva, FPV, Telzir); lopinavir/ritonavir (Kaletra, LPV/r)
Intervention MeSH terms: Ritonavir; Lopinavir; Atazanavir Sulfate; Fosamprenavir; Raltegravir Potassium; Efavirenz; Etravirine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: HIV; persistence; reservoirs; residual replication; gut; gut-associated lymphoid tissue; treatment experienced