title: A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.
abstract: BACKGROUND
  Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic.
  
  
  METHODS
  We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3) and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days.
  
  
  RESULTS
  Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20), -0.05(-0.21,+0.10), and +0.04(-0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred.
  
  
  CONCLUSIONS
  Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00428519.
authors.affiliation: Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. Pablo.tebas@uphs.upenn.edu
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Florin
authors.initials: F
authors.lastname: Tuluc
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Wayne
authors.initials: W
authors.lastname: Wagner
authors.forename: Deborah
authors.initials: D
authors.lastname: Kim
authors.forename: Huaquing
authors.initials: H
authors.lastname: Zhao
authors.forename: René
authors.initials: R
authors.lastname: Gonin
authors.forename: James
authors.initials: J
authors.lastname: Korelitz
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077608:Aprepitant; D018791:CD4 Lymphocyte Count; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D064729:Neurokinin-1 Receptor Antagonists; D010919:Placebos; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010919:Placebos; D018040:Receptors, Neurokinin-1; D000077608:Aprepitant