TY - JOUR
T1 - Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody
AU - Jacobson, Jeffrey M.
AU - Thompson, Melanie A.
AU - Lalezari, Jacob P.
AU - Saag, Michael S.
AU - Zingman, Barry S.
AU - D'Ambrosio, Paul
AU - Stambler, Nancy
AU - Rotshteyn, Yakov
AU - Marozsan, Andre J.
AU - Maddon, Paul J.
AU - Morris, Stephen A.
AU - Olson, William C.
N1 - Funding Information:
Financial support: National Institutes of Health (Public Health Service grant AI066329).
PY - 2010/5/15
Y1 - 2010/5/15
N2 - 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.
AB - 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.
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U2 - 10.1086/652190
DO - 10.1086/652190
M3 - Article
C2 - 20377413
AN - SCOPUS:77951916324
SN - 0022-1899
VL - 201
SP - 1481
EP - 1487
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -
