Journal article
Interactive selective pressures of HLA-restricted immune responses and antiretroviral drugs on HIV-1
Antiviral Therapy, Vol.10, pp.551-555
2005
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.
Details
- Title
- Interactive selective pressures of HLA-restricted immune responses and antiretroviral drugs on HIV-1
- Authors/Creators
- M. John (Author/Creator)C.B. Moore (Author/Creator)I.R. James (Author/Creator)S.A. Mallal (Author/Creator)
- Publication Details
- Antiviral Therapy, Vol.10, pp.551-555
- Publisher
- International Medical Press
- Identifiers
- 991005546342807891
- Copyright
- © 2005 International Medical Press
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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