Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice.
Cell
; 158(5): 989-999, 2014 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-25131989
ABSTRACT
Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
HIV Infections
/
HIV-1
/
Virus Latency
/
Antibodies, Neutralizing
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell
Year:
2014
Type:
Article
Affiliation country:
United States