M.G. Milia

Sequential therapy with entecavir and PEG-INF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes

Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa‐2a (PEG‐IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG‐IFN for 12 weeks, lastly PEG‐IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG‐IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti‐HBe seroconversion rate were 76.9% vs 15%, and anti‐HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes – genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG‐IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies.

HIV-1 Very Low Level Viremia is Associated with Virological Failure in HAART-treated Patients

Abstract The aim of this study was to evaluate the impact of HIV-1 very low-level viremia (<50 copies/ml) on the 2-year risk of virological failure. A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/ml (outpatient clinic in Italy, first semester of 2010) was performed. HIV RNA was measured through real time polymerase chain reaction (PCR) assay CAP/CTM HIV-1 version 2.0 (detection limit: 20 copies/ml) and stratified as undetectable RNA (“Target Not Detected”, TND), <20 copies/ml, 20–50 copies/ml. After 96 weeks virological failure was defined as two consecutive viral loads above 50 copies/ml. Log-rank tests and a multivariate Cox proportional hazard model were used for univariate and multivariate analysis. A total of 1,055 patients (71.4% male, 87.4% white, aged 46.7 years) were included: nadir and current CD4 cell counts were 203 cells/mm3 (106–292) and 554 cells/mm3 (413–713.5). HIV RNA was undetectable in 781 patients (74%), <20 copies/ml in 190...

Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009–2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.

Seminal pharmacokinetics and antiviral efficacy of once-daily maraviroc plus lopinavir/ritonavir in HIV-infected patients

mend a value of .100 for optimal fluconazole exposure when the MIC is tested using EUCAST methodology. Rough estimates of minimum AUC/MIC ratios of fluconazole against C. albicans isolated from bile and/or ascites [expressed as (bile or ascites Cmin.24 h)/MIC for Candida isolate in bile or ascites] were well above this threshold (.600) in our patients. We recognize that the absence of real AUC measurements may be a limitation, since our approach led to gross underestimation of drug exposure. However, the findings confirm the valuable role that fluconazole may have in the treatment of Candida cholangitis and/or peritonitis caused by susceptible strains in LTx patients, and supports the usefulness of TDM for optimizing fluconazole exposure in this setting.

A filter-based cross-sectional analysis of an HIV-positive, HAART-treated cohort in rural Burundi: pharmacokinetics, pharmacogenetics and viral load

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK