Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults.
J Infect Dis
; 198(9): 1345-52, 2008 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-18771406
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 310 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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1
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Anti-VIH
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Infecciones por VIH
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Fármacos Anti-VIH
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Anticuerpos Monoclonales
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Año:
2008
Tipo del documento:
Article