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

Academic Article

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 HIV-1 RNA levels of >5000 copies/mL, CD4(+) cell counts of >300 cells/microL, no receipt of antiretroviral therapy for >or=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 log(10) 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 .
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    Keywords

  • Adult, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, Female, HIV Antibodies, HIV Fusion Inhibitors, HIV Infections, HIV-1, Humans, Injections, Subcutaneous, Male, Middle Aged
  • Digital Object Identifier (doi)

    Author List

  • Jacobson JM; Thompson MA; Lalezari JP; Saag MS; Zingman BS; D'Ambrosio P; Stambler N; Rotshteyn Y; Marozsan AJ; Maddon PJ
  • Start Page

  • 1481
  • End Page

  • 1487
  • Volume

  • 201
  • Issue

  • 10