Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029.
Clin Microbiol Infect
; 21(1): 103.e1-6, 2015 Jan.
Article
in En
| MEDLINE
| ID: mdl-25636934
ABSTRACT
We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrug-experienced subjects were sequenced and the HIV-1-env gene cloned into pNL4.3Δenv to obtain recombinant viruses. The V3 region was sequenced by the Sanger method and ultradeep sequencing. By analysing subjects having a weighted optimized background therapy susceptibility (wOBT) score of <1, 3/7 subjects were characterized by good in vivo and in vitro response to maraviroc therapy. Molecular docking simulations allowed us to rationalize the maraviroc susceptibility of dual/mixed tropic viruses. A subset of subjects with dual/mixed tropic viruses responded to maraviroc. Further investigations are warranted of CCR5 antagonists in subjects carrying dual/mixed tropic virus that explore the feasible use of maraviroc in subjects that is potentially larger than those infected with a pure R5 virus.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triazoles
/
HIV Infections
/
HIV-1
/
Cyclohexanes
/
CCR5 Receptor Antagonists
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Clin Microbiol Infect
Journal subject:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Italia