Serum trimethylamine-N-oxide concentrations in people living with HIV and the effect of probiotics supplementation

Abstract Background: Cardiovascular disorders show a higher incidence in people living with HIV (PLWH). Traditional and specific risk factors have been described but the role of the gut microbiota-dependent choline metabolite trimethylamine-N-oxide (TMAO) is still unclear. Methods: A cross-sectional analysis and a longitudinal analysis (with high-dose probiotics supplementation) were performed measuring serum TMAO concentrations through UHPLC- MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used. Results: In 175 participants serum TMAO concentrations were 165 ng/mL (103-273). An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed: at linear logistic regression analysis, multimorbidity was theonly independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 mm (0.71-1.21); we observed a trend towards higher TMAO concentrations in patients with IMT >0.9 mm (p=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significant changed after 24 weeks (Wilcoxon paired p 0.220). Conclusion: Serum TMAO levels in PLWH are associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis; no effect of six months of high-dose probiotics supplementation was observed

Antiretroviral concentrations in the presence and absence of valproic acid

Objectives: An unexpected drug–drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. Methods: We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. Results: One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45–56) and 23.4 kg/m2 (20.8–26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62–227) in individuals on valproic acid versus 760 ng/mL (333–1407) in those not receiving valproic acid]. Conclusions: Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug–drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction

The value of combining the information content of analyst recommendations and target prices

10.1016/j.finmar.2009.07.002Journal of Financial Markets124754-77

Vitamin D in the COVID 19 prevention and treatment: emerging evidence

The significantly higher incidence of COVID-19 on mortality and morbidity observed in the northern Italian regions as compared to the southern ones, could be partly explained by geographic variations of the prevalence of vitamin D deficiency. The present opinion paper discusses this hypothesis. The immunomodulatory effects of vitamin D have been widely established and its benefits on viral and bacterial replication have been attributed to its ability to modulate gene expression by activating the vitamin D receptor in many target cells, including immune cells, and by promoting the expression of antimicrobial peptides such as cathelicidins and beta-defensins, which are also endowed with antiviral and immunomodulatory properties. Recently, following the onset of the COVID-19 pandemic situation, many studies have shown a high prevalence of very low levels of vitamin D in patients with severe manifestations of the disease, and that high dose vitamin D administration appeared able to favourably modify the evolution of the infection. Although these studies, mainly based on cross- sectional analyses and small-scale randomized clinical studies, could not provide a definitive proof of a cause-effect relationship, it is possible to suggest that hypovitaminosis D might be considered “guilty by association” as one of the factors able to worsen the pandemic spread and its clinical impact