Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.
AIDS Res Hum Retroviruses
; 31(10): 1032-7, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26258548
ABSTRACT
Around 2.5 million HIV-infected individuals failing first-line therapy qualify for boosted protease inhibitor (bPI)-based second-line therapy globally. Major resistance mutations are rarely present at treatment failure in patients receiving bPI and the determinants of failure in these patients remain unknown. There is evidence that Gag can impact PI susceptibility. Here, we have sequenced Gag-Protease before and following failure in 23 patients in the SARA trial infected with subtypes A, C, and D viruses. Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I and L63P. Following PI failure, previously described mutations in Protease and Gag were observed, including those at the cleavage sites such as R361K and P453L. However, the emergence of clear genetic determinants of therapy failure across patients was not observed. Larger Gag sequence datasets will be required to comprehensively identify mutational correlates of bPI failure across subtypes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Protease de HIV
/
Inibidores da Protease de HIV
/
Evolução Molecular
Limite:
Humans
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article