Antiviral therapy
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Comparative Study Clinical Trial
The influence of HIV infection and antiretroviral therapy on the mitochondrial membrane potential of peripheral mononuclear cells.
Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We analysed delta psi m, of peripheral blood mononuclear cells (PBMCs) in HIV-negative, healthy subjects (n=8), HIV-infected, treatment-naive patients (n=30), and HIV-infected patients on ART (n=58). The influence of ART was analysed in six patients who started their first regimen. ⋯ In HIV-infected persons delta psi m is significantly reduced. Patients with lipoatrophy have significantly reduced delta psi m. This is the first study showing that the delta psi m of PBMCs is highly correlated with CD4+ T-cell count in HIV infection.
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The VII International Symposium on Respiratory Viral Infections was a multidisciplinary forum for the presentation of recent advances in respiratory virus research with special emphasis on antiviral therapies and vaccine strategies. Topics covered in invited lectures included detection of novel respiratory viral pathogens and viral evolution, characterization of the 1918 pandemic virus, human metapneumovirus infections, human respiratory epithelial cultures for studying viral pathogenesis, the role of respiratory viruses in the pathogenesis of asthma, influenza-bacterial interactions, advances in generating vaccine candidates against global respiratory threats like avian influenza and SARS, antiviral resistance surveillance in influenza viruses, and a mini-symposium on advances in viral diagnostics. Other talks covered the live, attenuated intranasal influenza vaccine, monoclonals for respiratory syncytial virus (RSV), mechanisms of antiviral resistance in influenza B, and novel inhibitors for influenza, RSV and rhinovirus infections.
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To determine if the expression of CD38 on CD8+ T-cells could be used as a marker of viral replication <50 copies/ml in peripheral blood. ⋯ T-cell activation in patients on long-term successful ART is not due to residual low-level viral replication in the blood compartment of HIV-1. CD8+ T-cell activation in this patient group appears to be associated with poor CD4+ T-cell recovery.
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Oseltamivir phosphate is a prodrug of oseltamivir carboxylate, a highly specific inhibitor of influenza virus neuraminidases. Given that oseltamivir carboxylate binds to highly conserved, essential amino acids in the catalytic site of the enzyme, and that the activity of neuraminidase is critical for virus release from infected cells and subsequent virus spread, the drug was expected to have a low propensity to select for viable resistant mutants. Indeed, viruses with neuraminidase (and haemagglutinin) substitutions conferring reduced susceptibility to oseltamivir have been generated with difficulty in vitro, and these mutants generally have reduced infectivity and transmissibility compared with wild-type virus in animal models. ⋯ Higher incidences of resistance were observed in two small Japanese studies, in which children received a different dosing schedule from their Western counterparts. In summary, the overall incidence of influenza virus resistance associated with the seasonal use of oseltamivir is currently low and resistant viruses might be of little clinical significance, except perhaps in immunocompromised individuals. However, continued vigilance, especially of emerging avian H5N1 strains, combined with careful, systematic laboratory-based monitoring, is essential.
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Highly pathogenic H5N1 influenza viruses have become endemic in poultry populations throughout Southeast Asia and continue to infect humans with a greater than 50% case fatality rate. So far, human-to-human transmission of these viruses has been limited. Here, we discuss the molecular features of H5N1 influenza viruses that might affect their pathogenicity, and explain the current lack of efficient human-to-human transmission. Such knowledge is critical in evaluating the pandemic risk these viruses pose.