Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir.
J Antimicrob Chemother
; 73(10): 2716-2720, 2018 10 01.
Article
en En
| MEDLINE
| ID: mdl-30032194
ABSTRACT
Background:
Fostemsavir belongs to the new class of attachment inhibitors (AIs); it inhibits the entry of HIV into CD4+ T-lymphocytes by blocking conformational changes in gp120. This is a promising AI, but previous phenotypic data showed that genetically divergent HIV-1 group O could present natural resistance to this drug. These data were obtained from only two strains, which are not representative of the high intra-group genetic diversity. Moreover, no data are available concerning the other divergent HIV-1 groups (N and P).Objectives:
To further investigate the natural genotypic susceptibility of HIV-1 groups O, N and P (HIV-1 non-M) to fostemsavir, using a large set of sequences.Methods:
The frequency of eight substitutions associated with decreased susceptibility to fostemsavir (L116P, A204D, S375M/H, M426L, M434I, M475I and V506M), was investigated in 111 gp120 sequences from groups O (n = 100), N (n = 9) and P (n = 2).Results:
All HIV-1 group N sequences harboured the three substitutions S375M, M426L and M434I, whereas only 1% and 10% of HIV-1 group O sequences harboured the S375Hâ+âM426L and S375Hâ+âM434I patterns, respectively. The main genetic profile of HIV-1 groups P and O combined S375H with two atypical substitutions (M426S and M434L). Five group O sequences did not display any of the eight substitutions, but had atypical residues with unknown impact.Conclusions:
The genetic polymorphisms in the gp120 of HIV-1 non-M viruses support the hypothesis that these viruses could largely be resistant to inhibition by fostemsavir. Only 5% of group O strains could display full genetic susceptibility. Extensive phenotypic studies are now required.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Organofosfatos
/
Piperazinas
/
Polimorfismo Genético
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VIH-1
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Fármacos Anti-VIH
/
Farmacorresistencia Viral
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia