Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy.

OBJECTIVES: To assess the prevalence of hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) resistance mutations in HCV genotype 1-infected PI-naive individuals in Italy. PATIENTS AND METHODS: One hundred and twelve patients infected with HCV genotype 1a or 1b (based on Versant HCV Genotype 2.0 or 5'UTR/core sequencing) and never treated with any HCV PI were evaluated. The whole NS3 region was analysed by population sequencing and mutations related to resistance to linear and macrocyclic PIs were recorded. RESULTS: Forty-six HCV-monoinfected and 66 HCV/HIV-coinfected subjects were studied. Complete NS3 sequence information was obtained for 109 (97.3%) samples: 67 subtype 1a and 42 subtype 1b. Subtype assignment by NS3 sequencing was concordant in 100.0% and 83.9% of cases with the original 5'UTR sequencing and Versant result, respectively. At least one mutation related to PI resistance was detected in 21 (19.3%) isolates. However, 11 of these had only Q80K, expected to confer resistance to one investigational macrocyclic compound, and were detected only in subtype 1a. Boceprevir and telaprevir resistance-related mutations were detected in 10 (9.2%) isolates and included V36L, T54S and V55A. Only one isolate harboured two mutations (V36L and T54S). There was no association between HCV PI resistance and HIV coinfection or exposure to HIV PIs. CONCLUSIONS: A minority of untreated HCV genotype 1 patients in Italy harbour a virus population carrying HCV PI resistance-related mutations. The clinical implications of this finding warrant further analysis.

A novel approach to HIV therapy: highly active antiretroviral therapy and autologous hematopoietic cell transplantation.

Highly active antiretroviral therapy dramatically decreases in vivo viral replication to levels below the level of clinical detection, but does not eradicate HIV-1 infection on the basis of persistent low-level or cryptic viral replication and latent provirus in resting CD4+ T lymphocytes. Immune activation therapy has begun to be used in attempts to increase the turnover rate of the latent virus reservoir through activation of infected cells that comprise this reservoir, in order to promote cell death and accelerate virus clearance. Recent reports have not demonstrated complete virus ablation. Autologous hematopoietic cell transplantation now appears as a safe, feasible, and reasonable approach for Aids-related lymphoma in patients who meet criteria for transplantation. The hypothesis is based on the possibility that hematopoietic stem cells from a HIV-positive patient could be collected before the patient becomes infected with HIV. Then, the proposed treatment consists of the following assumptions. HAART keeps viral replication below the level of detection, limiting the infection to latent provirus in resting CD4+ T lymphocytes. It is presumed here that myeloablative conditioning regimen can lead to the killing of all the cells that, in theory, harbour the virus. The following transplantation of the autologous hematopoietic stem cells, collected before HIV infection, would allow the complete recovery. The hypothesis is to be tested on a suitable animal model. After the collection of hematopoietic stem cells, the animal is experimentally infected with the immunodeficiency virus. HAART is given after plasma viral RNA becomes detectable. By myeloablative conditioning regimen all the cells harbouring the virus are supposed to be killed. Then, as the viral load is kept undetectable by HAART, the animal undergoes autologous hematopoietic stem cell transplantation. Antiretroviral therapy is interrupted a month after engraftment has taken place. Although hematopoietic stem cells from man before infection with HIV are unlikely to be available, a successful test on the animal would suggest a new approach which could allow the cure of HIV in future.

Hepatotoxicity of Teucrium chamaedrys L. decoction: role of difference in the harvesting area and preparation method.

AIM: Two recurrent cases of severe acute liver injury attributed to the use of a wild germander decoction, prepared with some variation in traditional method has been reported. The aim of the present study was to correlate the hepatotoxic effect observed in patients who consumed germander decoction with teucrin A levels. Antioxidant properties were analyzed to assess any possible differences between the decoction used traditionally by the family (without negative consequences) and the decoction taken by the patients. MATERIALS AND METHODS: Different types of germander decoctions were prepared in the laboratory by simulating the same conditions for preparing the decoction by the patients and their family members. The levels of teucrin A, the polyphenols and the antioxidant power were determined. One-way analysis of variance was used to test for differences between the groups. RESULTS AND CONCLUSIONS: The extract consumed by the patients had higher concentration of teucrin A, lower antioxidant activity and lower content of polyphenols compared with the traditional decoction, revealing an inverse relationship between teucrin A content and antioxidant capacity. These case reports emphasize that more information is needed on the safety and quality of these natural products.

Imported dengue fever in Tuscany, Italy, in the period 2006 to 2012.

This report focuses on epidemiological and clinical features of dengue fever (DF) in Tuscany (Italy) between 2006 and 2012. Sixty-one DF cases were diagnosed, 32 of which were in the period of Aedes albopictus activity. Some clinical (arthralgia/myalgia, nausea/vomiting, and skin rash), laboratory (leukopenia and thrombocytopenia), and epidemiological characteristics (travel in a continent other than Africa) significantly distinguished DF cases from other febrile illnesses. Our data stress the importance of increasing awareness on dengue in Italy among clinicians in order to reach an early diagnosis in returning travelers and to implement appropriate clinical and public health interventions.