Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults

J Infect Dis. 2008 Nov 1;198(9):1345-52. doi: 10.1086/592169.


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.

Trial registration: ISRCTN Register: ISRCTN45537485 .

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacology*
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Resistance, Viral
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / pharmacology*
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Lymphocyte Count
  • Lymphocytes / immunology
  • Male
  • RNA, Viral / blood
  • Receptors, CCR5
  • Time Factors


  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • HIV Antibodies
  • RNA, Viral
  • Receptors, CCR5
  • leronlimab

Associated data

  • ISRCTN/ISRCTN45537485