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

Jeffrey M. Jacobson, Michael S. Saag, Melanie A. Thompson, Margaret A. Fischl, Ralph Liporace, Richard C. Reichman, Robert R. Redfield, Carl J. Fichtenbaum, Barry S. Zingman, Mahesh C. Patel, Jose D. Murga, Suzanne M. Pemrick, Paul D'Ambrosio, Marti Michael, Hans Kroger, Hieu Ly, Yakov Rotshteyn, Robert Buice, Stephen A. Morris, Joseph J. StavolaPaul J. Maddon, Alton B. Kremer, William C. Olson

Research output: Contribution to journalArticle

88 Scopus citations

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/μL, 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 log10, 1.20 log10 (P = .0002) and 1.83 log10 (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.

Original languageEnglish (US)
Pages (from-to)1345-1352
Number of pages8
JournalJournal of Infectious Diseases
Volume198
Issue number9
DOIs
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults'. Together they form a unique fingerprint.

  • Cite this

    Jacobson, J. M., Saag, M. S., Thompson, M. A., Fischl, M. A., Liporace, R., Reichman, R. C., Redfield, R. R., Fichtenbaum, C. J., Zingman, B. S., Patel, M. C., Murga, J. D., Pemrick, S. M., D'Ambrosio, P., Michael, M., Kroger, H., Ly, H., Rotshteyn, Y., Buice, R., Morris, S. A., ... Olson, W. C. (2008). Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults. Journal of Infectious Diseases, 198(9), 1345-1352. https://doi.org/10.1086/592169