Antiviral therapy
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Infection with influenza viruses, including seasonal, avian and pandemic viruses, remains a worldwide public health problem. Although influenza virus infection is both vaccine preventable and drug treatable, high rates of mutation and reassortment of viruses can result in reduced effectiveness of vaccines or drugs. Currently, two classes of drugs, adamantanes (M2 blockers) and neuraminidase (NA) inhibitors (NAIs), are available for treatment and chemoprophylaxis of influenza infections. ⋯ Nevertheless, the precise role of these genetic changes in the efficient transmission and maintenance of resistant viruses in the absence of drug pressure remains poorly understood. In this review, we summarize NAI resistance in influenza viruses and discuss recent challenges in laboratory testing methods. Close monitoring of antiviral resistance among all influenza viruses, both locally and globally, are essential to inform public health strategies for the control of influenza infections.
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Randomized Controlled Trial Multicenter Study
Switching to tenofovir/emtricitabine from abacavir/lamivudine in HIV-infected adults with raised cholesterol: effect on lipid profiles.
The aim of this study was to investigate the effect on fasting lipid parameters of switching to tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) from abacavir (ABC) plus lamivudine (3TC; both fixed-dose combinations), while maintaining ritonavir-boosted lopinavir (LPV/r). ⋯ Switching to TDF/FTC from ABC/3TC was associated with rapid improvements in fasting lipid parameters and continued virological control in patients receiving LPV/r as the third component of antiretroviral therapy. The effect of these changes on clinical end points remains unclear and would need to be evaluated in a longer-term study.
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Randomized Controlled Trial Comparative Study
Effect of oseltamivir, zanamivir or oseltamivir-zanamivir combination treatments on transmission of influenza in households.
The effectiveness of neuraminidase inhibitors to reduce transmission when used as treatment in influenza-infected patients remains debated. ⋯ Our analysis suggests a greater effectiveness of the combination therapy to reduce transmissibility when given to the index patient within 24 h of onset of symptoms. As the finding was obtained from a subgroup analysis, it should be interpreted with caution.
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Randomized Controlled Trial
Lactic acidosis and symptomatic hyperlactataemia in a randomized trial of first-line therapy in HIV-infected adults in South Africa.
Lactic acidosis (LA) is a potentially life-threatening complication of antiretroviral (ARV) therapy. Few randomized prospective studies have compared LA between different ARV regimens. ⋯ Female sex and increased BMI were associated with severe LA in this large randomized trial of first-line ARV in South Africa. While female sex, increased BMI and d4T are previously described risk factors for the development of clinically significant lactate elevations, the independent risk associated with EFV is a novel observation warranting further investigation.
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Boceprevir and telaprevir are the first HCV protease inhibitors to be approved for the treatment of chronic hepatitis C genotype 1 infection. These drugs must be used in combination with pegylated interferon plus ribavirin (P/R) to maximize efficacy and prevent the emergence of resistance-associated variants (RAVs). In randomized, placebo-controlled international studies in treatment-naive and previously treated HCV patients, treatment with either boceprevir- or telaprevir-based triple therapy regimens significantly increased sustained virological response rates compared with placebo plus P/R. ⋯ The emergence of RAVs was associated with an increased risk of virological failure in clinical studies. Although these new drugs bring significant promise, it remains unclear if all genotype 1 patients will need triple therapy. Here, we review some of the complexities uncovered and controversies highlighted by the introduction of HCV protease inhibitors.