In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients.
J Antimicrob Chemother
; 75(9): 2547-2553, 2020 09 01.
Article
em En
| MEDLINE
| ID: mdl-32464638
ABSTRACT
OBJECTIVES:
Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry.METHODS:
Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein.RESULTS:
Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55 years (52-61), time since HIV-1 diagnosis was 27 years (24-30), time on ART was 26 years (23-27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility.CONCLUSIONS:
These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Fármacos Anti-HIV
Limite:
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália