title: Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults.
abstract: BACKGROUND
  The current goal of human immunodeficiency virus type 1 (HIV-1) therapy is to maximally suppress viral replication. Securing this goal requires new drugs and treatment classes. The chemokine receptor CCR5 provides an entry portal for HIV-1, and PRO 140 is a humanized monoclonal antibody that binds to CCR5 and potently inhibits CCR5-tropic (R5) HIV-1 in vitro.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, dose-escalating study was conducted in 39 individuals with HIV-1 RNA levels or =5000 copies/mL, CD4(+) cell counts > or =250 cells/microL, no antiretroviral therapy for 3 months, and only R5 HIV-1 detectable. Cohorts were randomized 3:10 to receive placebo or doses of PRO 140 of 0.5, 2, or 5 mg/kg. Subjects were monitored for 58 days for safety, antiviral effects, and serum concentrations of PRO 140.
  
  
  RESULTS
  PRO 140 was generally well tolerated and demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Mean reductions in HIV-1 RNA level of 0.58 log(10), 1.20 log(10) (P= .0002) and 1.83 log(10) (P= .0001) were observed for the 0.5-, 2-, and 5-mg/kg dose groups, respectively. Reductions in mean viral load of > or =10-fold were observed within 4 days and persisted for 2-3 weeks after treatment.
  
  
  CONCLUSIONS
  This trial established clear proof of concept for PRO 140 as a potent antiretroviral agent with extended activity after a single dose.
  
  
  BACKGROUND
  ISRCTN Register: ISRCTN45537485 .
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA 19104, USA. jeffrey.jacobson@drexelmed.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Thompson
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
authors.forename: Ralph
authors.initials: R
authors.lastname: Liporace
authors.forename: Richard C
authors.initials: RC
authors.lastname: Reichman
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fichtenbaum
authors.forename: Barry S
authors.initials: BS
authors.lastname: Zingman
authors.forename: Mahesh C
authors.initials: MC
authors.lastname: Patel
authors.forename: Jose D
authors.initials: JD
authors.lastname: Murga
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Pemrick
authors.forename: Paul
authors.initials: P
authors.lastname: D'Ambrosio
authors.forename: Marti
authors.initials: M
authors.lastname: Michael
authors.forename: Hans
authors.initials: H
authors.lastname: Kroger
authors.forename: Hieu
authors.initials: H
authors.lastname: Ly
authors.forename: Yakov
authors.initials: Y
authors.lastname: Rotshteyn
authors.forename: Robert
authors.initials: R
authors.lastname: Buice
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Morris
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Stavola
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maddon
authors.forename: Alton B
authors.initials: AB
authors.lastname: Kremer
authors.forename: William C
authors.initials: WC
authors.lastname: Olson
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015483:HIV Antibodies; D012367:RNA, Viral; D019713:Receptors, CCR5; C420063:leronlimab