Antiviral therapy
-
Since the emergence of 2009 H1N1 virus, intravenous (IV) zanamivir has been authorized as an investigational treatment for patients with serious and life-threatening influenza through an Emergency Investigational New Drug application (EIND). This review encompasses the FDA's EIND database from May 2011 to June 2014. ⋯ IV zanamivir EIND authorizations were for treatment of critically ill adult patients with 2009 H1N1, including a substantial number with suspected oseltamivir resistance. Data from prospective, randomized controlled trials are needed and are ongoing to assess the safety and efficacy of IV zanamivir for treatment of hospitalized patients with severe influenza.
-
The incidence of HIV-associated dementia has decreased significantly with the introduction of combination antiretroviral therapy; however, milder or more subtle forms of neurocognitive disorders associated with HIV appear to remain common. There is a lack of consensus on when to screen and on which methods are most appropriate for identifying patients at risk of neurocognitive impairment. ⋯ It is important to identify these factors in order to apply relevant management strategies. In this review, we discuss a series of case studies that address some of the challenges presented by the diagnosis and management of HIV-associated neurocognitive impairment in different patient types.
-
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.
-
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.
-
Bacterial super-infections contribute to the significant morbidity and mortality associated with influenza and other respiratory virus infections. There are robust animal model data, but only limited clinical information on the effectiveness of licensed antiviral agents for the treatment of bacterial complications of influenza. ⋯ Basic and clinical research into viral-bacterial interactions over the past decade has revealed several mechanisms that underlie this synergism. By applying these insights to antiviral drug development, the potential exists to improve outcomes by means other than direct inhibition of the virus.