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Kappa opioid ligands as underexploited treatments of HIV-1 infection For those aged 25-44, HIV dropped from the leading cause of death in 1995 to third leading in 1996 and fifth leading in 1997. The age-adjusted HIV death rate of 5.9 deaths per 100,000 is the lowest rate since 1987; the first year mortality data were available for the disease. This dramatic reduction in AIDS related deaths has largely been due to the advent of anti-retroviral agents which prolong AIDS-free HIV infection as well as life-expectancy once AIDS has developed. Unfortunately the down side of this success is the appearance of drug resistance and consequently viral load eventually increases after prolonged and effective therapeutic intervention. Second line treatments should therefore be able to reduce the ability of HIV-1 to infect and replicate within host cells when viral load increases. Likewise treatments should also limit the development of HIV-related symptomology such as such as AIDS dementia. A small but convincing body of evidence suggests that kappa-opioid receptor agonists may meet both of these requirements. In 1996, kappa opioid ligands were reported to prevent HIV-1 expression in microglia.and consequent neurotoxic neural cell death. Kappa opioid ligands have also been shown to alter IL-6-induced HIV-1 expression in chronically infected promonocytes and HIV-1 expression in CD4 lymphocytes. Moreover opioid treatment has been shown to potentiate the efficacy of antiretroviral drugs. Most recently, kappa opioid ligands have been reported to inhibit HIV-1 entry into CD4 cells via down-regulation of CXCR4. Thus kappa opioid ligands demonstrate an exciting antiviral profile, blocking the ability of HIV-1 to infect and replicate within host cells and also preventing the neurotoxic effects of infection. This data suggests that kappa opioid ligands represent candidate adjuncts or back ups to standard antiviral therapies. Link to journal abstract:
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