Chronic infection with Hepatitis C virus (HCV) may lead to B-cells activation and transformation into non-Hodgkin lymphomas (NHL). Molecular mechanisms of B-cells transformation by HCV are poorly understood. One of the most common lymphoproliferative disorders in HCV-infected patients is splenic marginal zone lymphoma (SMZL). A case of a 42-years old man affected by HCV-related SMZL effectively treated with an IFN-free, NS3-NS4A inhibitor-based regimen is hereby described. The patient was treated for 16 weeks with faldaprevir, deleobuvir and ribavirin achieving a very rapid viral eradication without relevant toxicities. A rapid hematologic response was noted as well, with a statistically significant correlation between viral decay and lymphocyte improvement (coefficient r=0.55, p=0.042). The viral clearance led to SMZL cure even without the use of IFN. Thus, the causative role played by HCV in SMZL development is once again reinforced, whereas antiviral rather than anti-proliferative activity of IFN is indirectly proven. A regimen including DAAs should be considered when treating a HCV-related extra-hepatic disease.
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 patients motivation, and the sustainability of current and future therapies.
The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)-infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer-free, HIV-infected patients.
Cytomegalovirus (CMV) is a frequently encountered infection following hematopoietic cell transplantation, and tissue invasive pneumonia is a dreaded complication of the virus in this population. In this review of CMV pneumonia, we address epidemiology, pathogenesis, diagnostics, current therapy, and strategies to prevent the development of CMV. We also review emerging treatment and prevention options for this challenging disease.
Few data are available regarding the 10-year survival among subjects with HIV and cancer. The aim of this study was to evaluate the 10-year survival of HIV-infected subjects with AIDS-defining malignancies (ADM) or non-AIDS-defining malignancies (NADM). This was a single center, retrospective, observational study of subjects with HIV infection and a subsequent cancer diagnosis; the data were collected from January 1991 to April 2010. Malignancies were divided into ADM or NADM on the basis of the Centre of Diseases Control-1993 classification. Survival curves were estimated using Kaplan-Meyer method and compared by the log-rank test. Six hundred and fifteen (9.5%) of the 6,495 subjects recorded in the San Raffaele Infectious Diseases Database developed a malignancy: 431 (70%) an ADM and 184 (30%) a NADM. In the case of ADM, survival was more favorable when cancer was diagnosed during post-highly active antiretroviral therapy (HAART) era (10-year survival: 43.2% ± 4.4%) than when diagnosed during the pre-HAART era (10-year survival: 16.4% ± 2.7%; log-rank test: p < 0.001). The same was true in the case of NADM (10-year survival: 44.7% ± 5.5% vs. 33.3 ± 9.6%; log-rank test: p = 0.03). An evaluation of survival probability by cancer type showed higher survival rates during the post-HAART era in the case of non-Hodgkin lymphoma (10-year survival: 42.1% ± 5.3% vs. 11.4% ± 3.3%; log-rank test: p = <0.001), Kaposis sarcoma (10-year survival: 44.0% ± 8.4% vs. 23.5% ± 3.9%; log-rank test: p < 0.001) and Hodgkins disease (10-year survival: 49.5% ± 14.5% vs. 40.0% ± 12.7%; log-rank test: p = 0.005). Despite the better cancer prognosis during the post-HAART era, the 10-year survival of HIV-infected subjects with an ADM or NADM is poor.
In vitro studies have shown possible antiviral effects of tyrosine kinase inhibitors. In a retrospective study, we show that use of the tyrosine kinase inhibitor imatinib does not appear to reduce cytomegalovirus reactivation during the first 100 days after transplantation in a cohort of hematopoietic cell transplant recipients.
A significant improvement in the rate of eradication of Hepatitis C Virus Genotype 1 has been achieved with the addition of Boceprevir and Telaprevir to pegylated interferon and ribavirin. These two drugs are the heralds of a new wave of antivirals that will improve the efficacy of pegylated interferon or even will substitute this drug in interferon free combinations. The results of phase II studies in patients naïve to treatment seem to be very promising strongly supporting the possibility of a large success for a first line all oral antiviral combination in interferon naïve. However, data observed in interferon experienced patients are less exciting and probably more complex treatment regimens will be needed to treat this patients population.
Tenofovir disoproxil fumarate (TDF) is widely used in HIV-infected patients. It is associated with tubular toxicity, but its management is controversial. A possible strategy is to switch to a dual therapy based on lamivudine or emtricitabine (XTC) and protease inhibitors (PIs). A case-control study was designed to evaluate the switch to XTC + PI therapy in patients with TDF-related renal toxicity. A case was defined as a patient who was on TDF/XTC + PI and who switched to XTC + PI. A control was defined as a patient with the same clinical features who remained on TDF/XTC + PI. Twenty-one cases and 21 controls were included. After 48 weeks, no differences in efficacy were observed. No improvement in the glomerular filtration rate as estimated with the Cockroft-Gault formula (eGFR) was seen, but the number of times that patients had values below 60 ml/min was higher with standard TDF/XTC 1 PI treatment than with dual XTC + PI treatment. A switch to dual therapy could be an option for patients at risk of TDF-related renal damage with no relevant risk of virological or immunological failure.
Introduction of effective combined antiretroviral therapy has made human immunodeficiency virus (HIV) infection a chronic illness. Substantial reductions in the number of acquired immunodeficiency syndrome- (AIDS-) related deaths have been accompanied by an increase in liver-related morbidity and mortality. Liver diseases rank in the first three most-common causes of death in HIV-infected persons. Mortality is mainly due to cirrhosis and hepatocellular carcinoma induced by hepatitis C virus and hepatitis B virus coinfection. However, antiretroviral drugs toxicity also plays a role. Nonalcoholic fatty liver disease is a common cause of liver injury as well. Nevertheless, alcohol consumption probably plays a pivotal role. Noncirrhotic portal hypertension, an uncommon condition observed in less than 1% of patients, is increasingly described. Finally, acute hepatitis A virus (HAV) and acute and even chronic hepatitis E virus infection have also been reported as causes of liver damage in HIV. Anti-HAV vaccination is thus recommended in persons at risk living with HIV.
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