Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection.
Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4(+) T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.
Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY 10016, USA.
Saurabh
S
Mehandru
Brigitta
B
Vcelar
Terri
T
Wrin
Gabriela
G
Stiegler
Beda
B
Joos
Hiroshi
H
Mohri
Daniel
D
Boden
Justin
J
Galovich
Klara
K
Tenner-Racz
Paul
P
Racz
Mary
M
Carrington
Christos
C
Petropoulos
Hermann
H
Katinger
Martin
M
Markowitz
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000008:administration & dosage; D001780:Blood Coagulation Tests; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D024882:Drug Resistance, Viral; D041981:Gastrointestinal Tract; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D008297:Male; D055502:Secondary Prevention; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral