Antiviral therapy
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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.
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Randomized Controlled Trial Multicenter Study
Effect of an induction period of pegylated interferon-α2a and ribavirin on early virological response in HIV-HCV-coinfected patients: results from the CORAL-2 study.
It is uncertain whether a 4-week induction period of pegylated interferon and ribavirin increases early virological response (EVR) in HIV-HCV-coinfected patients. ⋯ A 4-week induction with pegylated interferon-α2a plus ribavirin was associated with a greater decrease in HCV RNA at week 4; however, this did not translate into higher EVR rates. Higher RBV doses and avoidance of NRTI-sparing antiretroviral regimens might improve HCV treatment efficacy.
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Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. ⋯ In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.
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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.