Interactive selective pressures of HLA-restricted immune responses and antiretroviral drugs on HIV-1.
Antivir Ther
; 10(4): 551-5, 2005.
Article
em En
| MEDLINE
| ID: mdl-16038481
ABSTRACT
HIV-specific cytotoxic T lymphocyte (CTL) responses mediated by human leukocyte antigen (HLA) recognition and antiretroviral drugs exert selection pressure on HIV-1 in vivo. The selection of CTL escape mutations strongly underpins the failure of CTL control in most untreated infections whilst drug-resistance mutations predict failure of drug control. These two evolutionary forces share common target residues in HIV-1 at which their selection effects could be synergistic or antagonistic, such that the propensity to develop drug resistance and virological treatment failure may be influenced by HLA type. We examined HIV-1 reverse transcriptase (RT) and protease sequences in a large clinical observational cohort of 487 HIV-infected individuals and found evidence of site-specific interactions between specific antiretroviral drug exposures, HLA alleles and HIV sequence diversity at population level. Such interactions may have general and specific implications for explaining in vivo/in vitro discordance of drug resistance, host-specific susceptibility to drug resistance, individualization of therapy and therapeutic vaccine design.
Buscar no Google
Bases de dados:
MEDLINE
Assunto principal:
Seleção Genética
/
HIV-1
/
Fármacos Anti-HIV
/
Farmacorresistência Viral
/
Antígenos HLA
Limite:
Humans
Idioma:
En
Revista:
Antivir Ther
Assunto da revista:
TERAPIA POR MEDICAMENTOS
/
VIROLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Austrália