Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults.
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 or =5000 copies/mL, CD4(+) cell counts > or =250 cells/microL, 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 log(10), 1.20 log(10) (P= .0002) and 1.83 log(10) (P= .0001) were observed for the 0.5-, 2-, and 5-mg/kg dose groups, respectively. Reductions in mean viral load of > or =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.


BACKGROUND
ISRCTN Register: ISRCTN45537485 .
Jacobson
Jeffrey M
JM
Drexel University College of Medicine, Philadelphia, PA 19104, USA. jeffrey.jacobson@drexelmed.edu
Saag
Michael S
MS
Thompson
Melanie A
MA
Fischl
Margaret A
MA
Liporace
Ralph
R
Reichman
Richard C
RC
Redfield
Robert R
RR
Fichtenbaum
Carl J
CJ
Zingman
Barry S
BS
Patel
Mahesh C
MC
Murga
Jose D
JD
Pemrick
Suzanne M
SM
D'Ambrosio
Paul
P
Michael
Marti
M
Kroger
Hans
H
Ly
Hieu
H
Rotshteyn
Yakov
Y
Buice
Robert
R
Morris
Stephen A
SA
Stavola
Joseph J
JJ
Maddon
Paul J
PJ
Kremer
Alton B
AB
Olson
William C
WC
D019380:Anti-HIV Agents / Q000097:blood / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5; D013997:Time Factors
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015483:HIV Antibodies; D012367:RNA, Viral; D019713:Receptors, CCR5; C420063:leronlimab