Efficacy of sofosbuvir-based therapies in HIV/HCV infected patients and persons who inject drugs.

In the era of Directly Acting anti HCV Antivirals treatment of hepatitis C is successful in the majority of persons treated. However, treatment of persons with HIV or who inject drugs remains challenging because of special issues: drug-drug interactions with antiretroviral, psychiatric and drug substitution therapies, treatment adherence, impact of treatment on HIV disease course or on risk of bacterial infections. Sofosbuvir induced sustained virologic response in 91% of 23 HIV/HCV coinfected persons treated in combination with ribavirin and pegylated interferon, in 83% of 497 treated in combination with ribavirin and in all 50 patients infected with HCV GT1 treated in combination with ledipasvir and ribavirin. The rates of efficacy in HCV-HIV coinfected were almost the same as those observed in HCV monoinfected suggesting that the efficacy of sofosbuvir is not reduced by HIV coinfection. There are no data on the efficacy of sofosbuvir in injection drugs users. The pangenotypic activity, the high barrier to resistance, the modest potential for drug-drug interactions makes sofosbuvir a reference drug for the treatment of these two special populations.

Optimizing treatment in HIV/HCV coinfection.

Sustained virological response (SVR) to anti-hepatitis C virus (HCV) treatment is an outcome that can improve life expectancy in persons with human immunodeficiency virus (HIV) infection. Results of anti-HCV treatment are poor, and less than 50% of treated patients show SVR to peginterferon plus ribavirin combination therapy; in infections from HCV genotype 1 this proportion is less than 40%. Pilot studies have demonstrated that Boceprevir or Telaprevir in combination with peginterferon plus ribavirin are able to increase the SVR rate from 45% to 74% with Telaprevir, and from 26% to 61% with Boceprevir in persons never treated for hepatitis C. Interim data seem to indicate a high rate of HCV RNA undetectability on treatment also in patients without sustained response to peginterferon plus ribavirin. Both Telaprevir and Boceprevir have drug-drug interactions with antiretrovirals, and options for concurrent antiretroviral therapy are restricted. There are also several new anti-HCV drugs under study with the potential for more tolerable effective future regimens. The indication for treatment in a patient with HCV/HIV coinfection should take into account the priority of treatment, the probability of sustained response, the potential toxicities, the concurrent antiretroviral therapy options, the patient's motivation, and the sustainability of current and future therapies.

Identification of taxine derivatives in biological fluids from a patient after attempted suicide by ingestion of yew (Taxus baccata) leaves.

The yew tree (Taxus baccata) is an evergreen conifer that is widespread over central and southern Europe. The toxic effects of this conifer and its leaves have been known since ancient times. The seeds are generally responsible for accidental intoxications in childhood, whereas the bark and the leaves are mainly used for homicidal or suicidal attempts. We investigated the metabolic pattern of taxines in a healthy 44-year-old male farmer who was admitted to Bergamo Emergency Department after attempting suicide. High-performance liquid chromatography was used to separate and identify taxine metabolites. Data reported in this paper confirmed that the patient attempted suicide by ingesting Taxus baccata leaves, which had been suggested by clinical examination. The most abundant free and conjugated taxine metabolites were characterized. The high concentration of conjugated metabolites found in urine underscores the critical role that conjugation in the liver plays in eliminating taxines and increasing the probability of the patient's survival.

Extracorporeal life support in a severe Taxus baccata poisoning.

INTRODUCTION: Yew (Taxus baccata) is a conifer known to be toxic since ancient times. Taxine A and taxine B, the toxic alkaloids of Taxus, block cardiac sodium and calcium channels causing nausea, vomiting, abdominal pain, cardiac arrhythmias, respiratory distress, coma, seizures, and death in yew poisoning. CASE REPORT: A 44-year-old male farmer was admitted to the hospital because of a suspected myocardial infarction. First bradycardia and then ventricular tachycardia were present and a severe right ventricular dilatation with biventricular dysfunction was observed but with normal coronary arteriography. He was resistant to conventional therapy and, 6 h after hospital admission, extracorporeal support with membrane oxygenation was applied. The patient recovered. Nine days later, a large number of yew leaves were unexpectedly observed in his feces. Botanical and laboratory analysis confirmed the poisoning. Blood (651 ng/mL) and urinary (5.6 mcg/mL) levels of 3,5-dimethoxyphenol (metabolite of taxicatine) were greater than previously reported in lethal cases. The patient was transferred to a psychiatric unit 17 days after admission. CONCLUSIONS: Intensive treatment of severe cardiovascular symptoms with antiarrhythmic drugs, temporary pacemaker, intra-aortic balloon pump, extracorporeal membrane oxygenation, and extracorporeal life support can be life-saving even after a potentially lethal ingestion of T. baccata leaves.