Background. Tenofovir is one of the most widely used antiretroviral drugs. Tenofovir undergoes renal clearance by a combination of glomerular filtrat

Ribavirin in combination with pegylated interferon α is the current standard treatment for chronic hepatitis C. Adequate exposure to ribavirin seems crucial for achieving the best virological response. However, anaemia is a frequent, dose-dependent limiting side effect of ribavirin use. Therefore, therapeutic drug monitoring of ribavirin plasma concentrations could be a useful tool for individualizing ribavirin dosing. Herein, we review the relationship between ribavirin plasma concentrations and both virological response and toxicity, in order to define an optimal therapeutic range for ribavirin.

Atazanavir seems to be a protease inhibitor (PI) with a more favourable metabolic profile. Information regarding the potential benefit of replacing lopinavir/ritonavir by atazanavir in HIV-infected patients with prolonged viral suppression is scarce. If proved, this strategy could be particularly attractive for the subset of patients with greater cardiovascular risk. SLOAT was a prospective, open, comparative trial in which patients receiving lopinavir/ritonavir-based regimens and having undetectable plasma HIV-RNA for longer than 24 weeks were randomized to continue on the same therapy or switch to atazanavir. Outcomes in viral rebound, CD4 counts, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose were compared in both groups of patients at 48 weeks of follow-up. A total of 189 patients were recruited and took at least the first dose of the assigned treatment arm. Overall, 102 switched to atazanavir (49 on 400 mg once daily, and 53 on 300 mg plus 100 mg of ritonavir once daily due to concomitant tenofovir use) and 87 continued on lopinavir/ritonavir. All patients received the PI along with two nucleoside analogues. Virological failure occurred in 12 patients switched to atazanavir and 9 continuing on lopinavir/ritonavir. A reduction (P < 0.001) in median total cholesterol (−19 mg/dL) and triglycerides (−80 mg/dL) was observed after 48 weeks of atazanavir switching, whereas no significant changes occurred in the lopinavir/ritonavir arm. Greater reductions in total cholesterol and triglycerides were seen in patients switched to atazanavir without ritonavir boosting. The replacement of lopinavir/ritonavir by atazanavir provides an overall significant reduction in total cholesterol and triglycerides, without increased risk of virological failure.

The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.

The activity of raltegravir and etravirine was assessed in vitro in HIV-1 group O isolates. Despite the presence of some natural polymorphisms associated with resistance to raltegravir (V72I, L74I, S153A, V201I, and T206S) and etravirine (G190A), both drugs showed significant antiviral activity. Subsequently, the clinical benefit was shown in an HIV-1 group O-infected individual in whom enfuvirtide was replaced by raltegravir. Therefore, individuals infected with HIV-1 group O might benefit from raltegravir and/or etravirine therapy.

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.