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

Academic Article

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. TRIAL REGISTRATION: ISRCTN Register: ISRCTN45537485 .
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    Keywords

  • Anti-HIV Agents, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Area Under Curve, Dose-Response Relationship, Drug, Double-Blind Method, Drug Resistance, Viral, Female, HIV Antibodies, HIV Infections, HIV-1, Humans, Lymphocyte Count, Lymphocytes, Male, RNA, Viral, Receptors, CCR5, Time Factors
  • Digital Object Identifier (doi)

    Author List

  • Jacobson JM; Saag MS; Thompson MA; Fischl MA; Liporace R; Reichman RC; Redfield RR; Fichtenbaum CJ; Zingman BS; Patel MC
  • Start Page

  • 1345
  • End Page

  • 1352
  • Volume

  • 198
  • Issue

  • 9