title: Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody.
abstract: BACKGROUND
  PRO 140 is a humanized CCR5 monoclonal antibody that has demonstrated potent antiviral activity when it is administered intravenously to adults infected with CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1). This study is the first to evaluate subcutaneous administration.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled study was conducted among 44 subjects with HIV-1 RNA levels of >5000 copies/mL, CD4(+) cell counts of >300 cells/microL, no receipt of antiretroviral therapy for >or=12 weeks, and only R5 HIV-1 detectable. Subjects received placebo, 162 mg of PRO 140, or 324 mg of PRO 140 weekly for 3 weeks or 324 mg of PRO 140 every other week for 2 doses by means of subcutaneous infusion. Subjects were monitored for 58 days for safety, antiviral effects, and PRO 140 serum concentrations.
  
  
  RESULTS
  Subcutaneous PRO 140 demonstrated potent and prolonged antiretroviral activity. Mean log(10) reductions in HIV-1 RNA level were 0.23, 0.99 (P=.009), 1.37 (P<.001), and 1.65 (P<.001) for the placebo, 162 mg weekly, 324 mg biweekly, and 324 mg weekly dose groups, respectively. Viral loads remained suppressed between successive doses. Treatment was generally well tolerated.
  
  
  CONCLUSIONS
  This trial demonstrates proof of concept for a monoclonal antibody administered subcutaneously in HIV-1 infected individuals. Subcutaneous PRO 140 offers the potential for significant dose-dependent HIV-1 RNA suppression and infrequent patient self-administration.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00642707 .
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania 19104, USA. jeffrey.jacobson@drexelmed.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Thompson
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Barry S
authors.initials: BS
authors.lastname: Zingman
authors.forename: Paul
authors.initials: P
authors.lastname: D'Ambrosio
authors.forename: Nancy
authors.initials: N
authors.lastname: Stambler
authors.forename: Yakov
authors.initials: Y
authors.lastname: Rotshteyn
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Marozsan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maddon
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Morris
authors.forename: William C
authors.initials: WC
authors.lastname: Olson
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D004334:Drug Administration Schedule; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage* / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015483:HIV Antibodies; D023581:HIV Fusion Inhibitors; C420063:leronlimab