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. Stavola & 3 others Paul J. Maddon, Alton B. Kremer, William C. Olson

Research output: Contribution to journalArticle

86 Citations (Scopus)

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

Fingerprint

Antiviral Agents
HIV-1
Monoclonal Antibodies
HIV
Placebos
RNA
Anti-Retroviral Agents
Antibodies, Monoclonal, Humanized
Chemokine Receptors
Therapeutics
CD4 Lymphocyte Count
Viral Load
PRO-140 monoclonal antibody
Safety
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Jacobson, J. M., Saag, M. S., Thompson, M. A., Fischl, M. A., Liporace, R., Reichman, R. C., ... 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

Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults. / Jacobson, Jeffrey M.; Saag, Michael S.; Thompson, Melanie A.; Fischl, Margaret A.; Liporace, Ralph; Reichman, Richard C.; Redfield, Robert R.; Fichtenbaum, Carl J.; Zingman, Barry S.; Patel, Mahesh C.; Murga, Jose D.; Pemrick, Suzanne M.; D'Ambrosio, Paul; Michael, Marti; Kroger, Hans; Ly, Hieu; Rotshteyn, Yakov; Buice, Robert; Morris, Stephen A.; Stavola, Joseph J.; Maddon, Paul J.; Kremer, Alton B.; Olson, William C.

In: Journal of Infectious Diseases, Vol. 198, No. 9, 01.11.2008, p. 1345-1352.

Research output: Contribution to journalArticle

Jacobson, JM, Saag, MS, Thompson, MA, Fischl, MA, Liporace, R, Reichman, RC, Redfield, RR, Fichtenbaum, CJ, Zingman, BS, Patel, MC, Murga, JD, Pemrick, SM, D'Ambrosio, P, Michael, M, Kroger, H, Ly, H, Rotshteyn, Y, Buice, R, Morris, SA, Stavola, JJ, Maddon, PJ, Kremer, AB & Olson, WC 2008, 'Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults', Journal of Infectious Diseases, vol. 198, no. 9, pp. 1345-1352. https://doi.org/10.1086/592169
Jacobson JM, Saag MS, Thompson MA, Fischl MA, Liporace R, Reichman RC et al. Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults. Journal of Infectious Diseases. 2008 Nov 1;198(9):1345-1352. https://doi.org/10.1086/592169
Jacobson, Jeffrey M. ; Saag, Michael S. ; Thompson, Melanie A. ; Fischl, Margaret A. ; Liporace, Ralph ; Reichman, Richard C. ; Redfield, Robert R. ; Fichtenbaum, Carl J. ; Zingman, Barry S. ; Patel, Mahesh C. ; Murga, Jose D. ; Pemrick, Suzanne M. ; D'Ambrosio, Paul ; Michael, Marti ; Kroger, Hans ; Ly, Hieu ; Rotshteyn, Yakov ; Buice, Robert ; Morris, Stephen A. ; Stavola, Joseph J. ; Maddon, Paul J. ; Kremer, Alton B. ; Olson, William C. / Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults. In: Journal of Infectious Diseases. 2008 ; Vol. 198, No. 9. pp. 1345-1352.
@article{2f3a1242ae0b47c5afe57202f5b699e2,
title = "Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults",
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.",
author = "Jacobson, {Jeffrey M.} and Saag, {Michael S.} and Thompson, {Melanie A.} and Fischl, {Margaret A.} and Ralph Liporace and Reichman, {Richard C.} and Redfield, {Robert R.} and Fichtenbaum, {Carl J.} and Zingman, {Barry S.} and Patel, {Mahesh C.} and Murga, {Jose D.} and Pemrick, {Suzanne M.} and Paul D'Ambrosio and Marti Michael and Hans Kroger and Hieu Ly and Yakov Rotshteyn and Robert Buice and Morris, {Stephen A.} and Stavola, {Joseph J.} and Maddon, {Paul J.} and Kremer, {Alton B.} and Olson, {William C.}",
year = "2008",
month = "11",
day = "1",
doi = "10.1086/592169",
language = "English (US)",
volume = "198",
pages = "1345--1352",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "9",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=54249125999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54249125999&partnerID=8YFLogxK

U2 - 10.1086/592169

DO - 10.1086/592169

M3 - Article

VL - 198

SP - 1345

EP - 1352

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 9

ER -