Antiviral therapy
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Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. ⋯ Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.
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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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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.
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In haematopoietic stem cell transplant (HSCT) recipients, cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in both the early and late post-transplant period. Ganciclovir (GCV) is the treatment of choice for CMV, but requires intravenous administration, a fact that complicates its long-term use. Oral valganciclovir (VGCV) and intravenous GCV were recently shown to have similar efficacy for pre-emptive CMV treatment in solid organ transplant recipients, but relatively limited data are available in HSCT recipients. The objectives of this study were to compare the efficacy of VGCV versus intravenous GCV or foscarnet (FOS) for pre-emptive therapy of active CMV infection in allogeneic HSCT and to determine the incidence of adverse effects and relapses. ⋯ In allogeneic HSCT recipients, VGCV seemed effective and safe in the pre-emptive therapy of active CMV infection.