Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody

Jeffrey M. Jacobson, Melanie A. Thompson, Jacob P. Lalezari, Michael S. Saag, Barry S. Zingman, Paul D'Ambrosio, Nancy Stambler, Yakov Rotshteyn, Andre J. Marozsan, Paul J. Maddon, Stephen A. Morris, William C. Olson

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Background. PRO 140 is a humanized CCR5 monoclonal antibody that has demonstrated potent antiviral activity when it is administered intravenously to adults infected with CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1). This study is the first to evaluate subcutaneous administration. Methods. A randomized, double-blind, placebo-controlled study was conducted among 44 subjects with HIV1 RNA levels of >5000 copies/mL, CD4+ cell counts of >300 cells/μL, no receipt of antiretroviral therapy for ≥ 12 weeks, and only R5 HIV-1 detectable. Subjects received placebo, 162 mg of PRO 140, or 324 mg of PRO 140 weekly for 3 weeks or 324 mg of PRO 140 every other week for 2 doses by means of subcutaneous infusion. Subjects were monitored for 58 days for safety, antiviral effects, and PRO 140 serum concentrations. Results. Subcutaneous PRO 140 demonstrated potent and prolonged antiretroviral activity. Mean log10 reductions in HIV-1 RNA level were 0.23, 0.99 (P = .009), 1.37 (P<.001), and 1.65 (P<.001) for the placebo, 162 mg weekly, 324 mg biweekly, and 324 mg weekly dose groups, respectively. Viral loads remained suppressed between successive doses. Treatment was generally well tolerated. Conclusions. This trial demonstrates proof of concept for a monoclonal antibody administered subcutaneously in HIV-1 infected individuals. Subcutaneous PRO 140 offers the potential for significant dose-dependent HIV-1 RNA suppression and infrequent patient self-administration. Trial registration. ClinicalTrials.gov identifier: NCT00642707.

Original languageEnglish (US)
Pages (from-to)1481-1487
Number of pages7
JournalJournal of Infectious Diseases
Volume201
Issue number10
DOIs
StatePublished - May 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody'. Together they form a unique fingerprint.

Cite this