Journal article
Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults
The Journal of infectious diseases, v 198(9), pp 1345-1352
01 Nov 2008
PMID: 18771406
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 >= 5000 copies/mL, CD4(+) cell counts >= 250 cells/mu L, 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-1RNA 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 >= 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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Details
- Title
- Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults
- Creators
- Jeffrey M. Jacobson - Drexel UniversityMichael S. Saag - University of Alabama at BirminghamMelanie A. Thompson - AIDS Research Consortium of AtlantaMargaret A. Fischl - University of Miami*Ralph Liporace - Albany Medical Center HospitalRichard C. Reichman - University of RochesterRobert R. Redfield - University of Maryland, BaltimoreCarl J. Fichtenbaum - University of CincinnatiBarry S. Zingman - Yeshiva UniversityMahesh C. Patel - Jacobi Medical CenterJose D. Murga - Progenics PharmaceuticalsSuzanne M. Pemrick - Progenics PharmaceuticalsPaul D'Ambrosio - Progenics PharmaceuticalsMarti Michael - Progenics PharmaceuticalsHans Kroger - Progenics PharmaceuticalsHieu Ly - Progenics PharmaceuticalsYakov Rotshteyn - Progenics PharmaceuticalsRobert Buice - Progenics PharmaceuticalsStephen A. Morris - Progenics PharmaceuticalsJoseph J. Stavola - Progenics PharmaceuticalsPaul J. Maddon - Progenics PharmaceuticalsAlton B. Kremer - Progenics PharmaceuticalsWilliam C. Olson - Progenics PharmaceuticalsMarla A Thompson - College of Engineering (1970-)
- Publication Details
- The Journal of infectious diseases, v 198(9), pp 1345-1352
- Publisher
- Oxford Univ Press
- Number of pages
- 8
- Grant note
- AI066329 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Engineering
- Web of Science ID
- WOS:000260030200014
- Scopus ID
- 2-s2.0-54249125999
- Other Identifier
- 991019168979504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Microbiology