Sabrina Audagnotto

A short course of pegylated interferon-alpha in acute HCV hepatitis

Summary.  Acute hepatitis C virus (HCV) infection evolves to chronicity in 50–84% cases. Treatment with interferon‐α (IFN‐α) was repeatedly found to provide sustained cure rates higher than that in chronic HCV infection, but the optimal treatment strategy has not yet been defined. In a multicentre open‐label study, we investigated the therapeutic performance of a short course of pegylated (peg) IFN‐α in patients with acute HCV hepatitis. Peg IFN‐α2b, 1.0–1.5 μg/kg weekly, was administered for 12 weeks. Forty‐six patients were enrolled; 26 of them were intravenous drug users. Eleven patients had jaundice. Treatment was started within 1–90 days from the peak alanine aminotransferase. Treatment was well tolerated with a single dropout (2%). Thirty‐three of 46 patients (72%) had a sustained virological response (SVR) after a 6 months post‐treatment follow‐up, 8 (17%) relapsed after treatment and 4 were nonresponders (9%). A lower peak viraemia, receiving at least 1.2 μg/kg of peg IFN‐α, and a negative HCV‐RNA at week 4 and week 12 were predictors of SVR. Thus, in patients with early (week 4) viral response, a short course of peg IFN‐α at a weekly dose >1.2 μg/kg, may be a valuable option for the treatment of acute HCV hepatitis.

Twelve-Week Treatment of Acute Hepatitis C Virus with Pegylated Interferon-α-2b in Injection Drug Users

Injection drug use is the leading risk factor for infection with hepatitis C virus, and interferon (IFN) treatment in this context is associated with a poor rate of adherence. In this article, we review our experience with injection drug users with acute hepatitis C who are treated with pegylated IFN- alpha -2b for 12 weeks. Acute hepatitis C was diagnosed according to standardized criteria, and patients were treated with a median dosage of IFN- alpha -2b of 1.33 microg/kg per week. A sustained virological response was achieved in 17 (74%) of 23 patients. A sustained virological response was achieved in 14 (87%) of 16 patients treated with a dosage of >or=1.33 microg/kg per week and in 3 (43%) of 7 patients treated with a lower dosage. Sustained virological response was significantly associated only with a pegylated IFN- alpha -2b dosage >or=1.33 microg/kg per week (P=.022). A 12-week regimen of pegylated IFN to treat injection drug users with hepatitis C has a compliance that is much higher than that reported with a 24-week regimen. Adverse effects are minimal if patients are carefully selected.

Infective endocarditis in intravenous drug users from Italy: the increasing importance in HIV-infected patients.

Background:Intravenous drug users (IDUs) are at increased risk of infective endocarditis (IE).Patients and Methods:Episodes of IE in IDUs were retrospectively analyzed in this multicenter study. Cases were collected between 1986 and 1999. Only definite diagnosis according to the Duke criteria were analyzed.Results:Two hundred and sixty-three cases, including 100 cases in HIV-positive patients, were observed in IDUs. Any right-sided involvement was detected in 167 out of 263 cases (63.5%) and any left-sided involvement in 115 out of 263 cases (43.7%). The tricuspid valve (TV) alone was affected in 135 cases (51.3%), the mitral valve alone in 32 patients (12.1%), the aortic valve alone in 41 cases (15.6%) and the pulmonic valve alone in 3 cases. Staphylococcus aureus was isolated in 156 cases (59.3%) and Streptococcus spp. in 33 cases (12.5%). No major differences were observed between HIV-negative and HIV-positive patients. Any TV valve involvement was significantly associated with female rather than male gender (p = 0.02). There was a significant association between S. aureus etiology and TV involvement (p < 0.0001). The mortality rate was 16%. On multivariate analysis, only left-side IE (p = 0.0006; OR 5.2; 95% CI 2.0–13.5) and age greater than 35 years (p = 0.0068; OR 3.6; 95% CI 1.4–9.0) were independently associated with mortality.Conclusions:Infective endocarditis in IDUs is significantly associated with right-side localization (63.5% for any rightsided heart involvement vs 43.7% for any left-sided heart involvement; OR 2.24; 95% CI 1.55–3.23; p < 0.001). S. aureus is the microorganism most frequently isolated and is significantly associated with TV involvement. Any left-side involvement and age greater than 35 years are independently associated with mortality. HIV infection does not appear to have a significant effect on mortality.

High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis.

OBJECTIVES To analyse the determinants of raltegravir CSF penetration, including the pharmacogenetics of drug transporters located at the blood-brain barrier or blood-CSF barrier. METHODS Plasma and CSF raltegravir concentrations were determined by a validated HPLC coupled with mass spectrometry method in adults on raltegravir-based combination antiretroviral therapy undergoing a lumbar puncture. Single nucleotide polymorphisms in the genes encoding drugs transporters (ABCB1 3435, SLCO1A2, ABCC2 and SLC22A6) and the gene encoding hepatocyte nuclear factor 4 α (HNF4α) were determined by real-time PCR. RESULTS In 41 patients (73.2% male, 95.1% Caucasians), the median raltegravir plasma and CSF concentrations were 165 ng/mL (83-552) and 31 ng/mL (21-56), respectively. CSF-to-plasma ratios (CPRs) ranged from 0.005 to 1.33 (median 0.20, IQR 0.04-0.36). Raltegravir trough CSF concentrations (n = 35) correlated with raltegravir plasma levels (ρ = 0.395, P = 0.019); CPRs were higher in patients with blood-brain barrier damage (0.47 versus 0.18, P = 0.02). HNF4α 613 CG genotype carriers had lower trough CSF concentrations (20 versus 37 ng/mL, P = 0.03) and CPRs (0.12 versus 0.27, P = 0.02). Following multivariate linear regression analysis, the CSF-to-serum albumin ratio was the only independent predictor of raltegravir penetration into the CSF. CONCLUSIONS Raltegravir penetration into the CSF shows a large interpatient variability, although CSF concentrations were above the wild-type IC50 in all patients (and above IC95 in 28.6%). In this cohort, blood-brain barrier permeability is the only independent predictor of raltegravir CPR. The impact of single nucleotide polymorphisms in selected genes on raltegravir penetration warrants further studies.

Blackwater fever in children, Burundi.

Blackwater fever is characterized by acute intravascular hemolysis with hemoglobinuria in patients with Plasmodium falciparum malaria. Its pathogenesis and management are still debated. Nine cases of this syndrome occurred in 2003 at Kiremba Hospital in Burundi in children receiving multiple quinine treatments.

Louseborne Relapsing Fever among East African Refugees, Italy, 2015

During June 9–September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Drug-drug interactions and tolerance in combining antituberculosis and antiretroviral therapy.

Worldwide, tuberculosis (TB) is one of the most important infectious diseases in subjects with HIV infection. Although effective therapy is available for both conditions, there are major problems in the concurrent treatment of HIV and TB co-infection. In this article the knowledge available on drug–drug interactions between anti-HIV and anti-TB compounds is analysed, particularly with regard to pharmacological interactions secondary to interference with cytochrome P450 enzymes. Within the same setting, facts and possible interpretations of the problems encountered in terms of tolerance and safety of the concurrent treatment of TB and HIV are also reviewed. Current guidelines, as well as additional possible strategies to be adopted in this particular co-morbidity setting are discussed.

Clearance of 14-3-3 Protein from Cerebrospinal Fluid Heralds the Resolution of Bacterial Meningitis

The 14-3-3 protein, a cerebrospinal fluid (CSF) marker of neuronal damage that was recently adopted for the diagnosis of Creutzfeldt-Jakob disease, is also found in the CSF of patients with a variety of neurological disorders. We prospectively studied 12 consecutive patients with purulent bacterial meningitis and found that 14-3-3 protein was detected in all patients at admission to the hospital. All patients who recovered cleared 14-3-3 protein from the CSF before discharge from the hospital (this was the first CSF marker to clear), whereas those who died never cleared the protein.

Voriconazole and atazanavir: a CYP2C19-dependent manageable drug–drug interaction

AIM To investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype. MATERIALS & METHODS We describe four HIV-positive patients with pulmonary aspergillosis treated with voriconazole and atazanavir-based regimens (with or without ritonavir). They were managed by assessing their CYP2C19 genotype (CYP2C19*2, rs4244285, G>A, real-time PCR) and therapeutic drug monitoring (HPLC-based validation methods). RESULTS & CONCLUSION Voriconazole exposure was variable but Ctrough levels were above 1000 ng/ml in all patients; one CYP2C19 intermediate metabolizer required lower doses of voriconazole (50 mg twice daily) to obtain satisfactory drug concentrations. Atazanavir and ritonavir plasma levels were moderately reduced (area under the curve: -23 and -26%, respectively); raltegravir exposure seemed increased by voriconazole administration (area under the curve: 2.5-fold higher) in a single subject. Coadministration of atazanavir and voriconazole may be feasible in selected HIV-positive patients; therapeutic drug monitoring and CYP2C19 genotyping may optimize exposure of both drugs.

Cerebrospinal fluid biomarkers in patients with plasma HIV RNA below 20 copies/mL

Low level HIV‐1 CSF replication (CsfLLV) is often found even in patients with controlled plasma viraemia. The clinical consequences of such finding are uncertain; however, both symptomatic neurological disturbances and neurocognitive disorders may arise in the context of CSF‐escape. Two reports suggested that low level replication in the CSF may be associated with increased CSF neopterine although the impact on other markers of neuroinflammation/damage is currently unknown.