Antiviral Activity of Single‐Dose PRO 140, a CCR5 Monoclonal Antibody, in HIV‐Infected Adults

Authors:
  • MSMichael S. Saag
    Michael S. Saag
  • MTMelanie A. Thompson
    Melanie A. Thompson
  • MFMargaret A. Fischl
    Margaret A. Fischl
  • RLRalph Liporace
    Ralph Liporace
  • RRRichard C. Reichman
    Richard C. Reichman
  • RRRobert R. Redfield
    Robert R. Redfield
  • BZBarry S. Zingman
    Barry S. Zingman
  • MPMahesh C. Patel
    Mahesh C. Patel
  • JMJose D. Murga
    Jose D. Murga
  • SPSuzanne M. Pemrick
    Suzanne M. Pemrick
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Abstract
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. 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. 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. This trial established clear proof of concept for PRO 140 as a potent antiretroviral agent with extended activity after a single dose. ISRCTN Register: ISRCTN45537485 .

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