TY - JOUR
T1 - Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults
AU - Jacobson, Jeffrey M.
AU - Saag, Michael S.
AU - Thompson, Melanie A.
AU - Fischl, Margaret A.
AU - Liporace, Ralph
AU - Reichman, Richard C.
AU - Redfield, Robert R.
AU - Fichtenbaum, Carl J.
AU - Zingman, Barry S.
AU - Patel, Mahesh C.
AU - Murga, Jose D.
AU - Pemrick, Suzanne M.
AU - D'Ambrosio, Paul
AU - Michael, Marti
AU - Kroger, Hans
AU - Ly, Hieu
AU - Rotshteyn, Yakov
AU - Buice, Robert
AU - Morris, Stephen A.
AU - Stavola, Joseph J.
AU - Maddon, Paul J.
AU - Kremer, Alton B.
AU - Olson, William C.
N1 - Funding Information:
Financial support: National Institutes of Health (Public Health Service grant AI066329).
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
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U2 - 10.1086/592169
DO - 10.1086/592169
M3 - Article
C2 - 18771406
AN - SCOPUS:54249125999
SN - 0022-1899
VL - 198
SP - 1345
EP - 1352
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -
