Article

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

Drexel University College of Medicine, Philadelphia, PA 19104, USA.
The Journal of Infectious Diseases (impact factor: 6.41). 10/2008; 198(9):1345-52. DOI:10.1086/592169
Source: PubMed

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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Keywords

2-3 weeks
 
4 days
 
5-mg/kg dose groups
 
antiretroviral therapy
 
antiviral effects
 
chemokine receptor CCR5
 
dose-dependent antiviral activity
 
dose-escalating study
 
entry portal
 
HIV-1 RNA level
 
HIV-1 RNA levels
 
humanized monoclonal antibody
 
Mean reductions
 
new drugs
 
potent antiretroviral agent
 
potently inhibits CCR5-tropic
 
R5 HIV-1 detectable
 
treatment classes
 
viral load
 
viral replication