Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients with hepatitis C recurrence: safety, efficacy and long-term outcome.

BACKGROUND: There is limited information on the long-term outcome in liver transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to full dose pegylated interferon/ribavirin (peg-IFN/RBV). METHODS: Retrospective review of eight LT subjects after PSE and antiviral therapy. RESULTS: Baseline platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and 50%. Mean splenic infarction volume was 85 +/- 13%. PSE produced major complications in three (37.5%): recurrent sterile netrophilic ascites and renal insufficiency (n = 2), and splenic abscess (n = 1). Full-dose peg-IFN/RBV was started in seven (87.5%), with two early withdrawals (28.6%) despite early virological response (toxicity and infection); both subjects died. Anemia led to RBV dose-adjustment in six (86%), with human recombinant erythropoietin (EPO) use in four (57%). No peg-IFN adjustments or granulocyte-colonies stimulating factor were needed. Two patients reached sustained virological response (SVR) (28.6%). Two non-responders maintained prolonged therapy with biochemical/histological improvement. After a median follow-up of 151 wk, we observed significant improvements in hematological parameters, aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and prothrombin activity. CONCLUSIONS: Extensive PSE after LT produced significant morbidity (37.5%). Peg-IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV adjustement due to anemia was high despite EPO use. Only patients able to complete or maintain antiviral therapy survived, with long-term significant benefits in hematological parameters and liver function tests.

Long-term improvement in renal, bone, lipid parameters, and CD4/CD8 ratio in HIV-infected patients switching to a dual therapy with lamivudine plus boosted darunavir.

BACKGROUND: Dual therapies have been tested in selected patients, but there is no evidence for its advantages in clinical practice. The aim of this study was to evaluate in the clinical setting the long-term outcomes and the impacts on comorbidities of a dual therapy based on lamivudine plus darunavir boosted with ritonavir (DRV/r). METHODS: A prospective cohort study of 106 patients who were switched to this dual regimen from April 2014 to December 2017 because of renal and bone toxicity, intolerance, or physician's decision was conducted. The primary study endpoint was the proportion of patients who were free of treatment failure at 48 and 96 weeks. RESULTS: The mean age was 50 years, and 64% were hepatitis C virus-coinfected. At 48 weeks, the efficacy was 95% (95% confidence interval, 91-99%; ITT-e analysis; two changes due to toxicity, three because of drug-drug interactions -DDIs-). At week 96, 26 patients (25%) had discontinued this therapy (two virologic failures, one additional adverse event, 18 therapy changes to avoid DDIs). An increase in lipid parameters was observed during the first 6-12 months in the group discontinuing tenofovir disoproxil fumarate (p < .01), which was partly corrected at 96 weeks. Improvements in CD4/CD8 ratio (p = .04), bone mineral density (+1.17%; p = .07), estimated glomerular filtration rate (+7.7 mL/min in CKD patients; p = .02), urinary parameters (proteinuria, -23%), and overall cost (-43%) were observed. CONCLUSIONS: Our results demonstrated the long-term efficacy and safety of an antiretroviral regimen based on dual therapy with lamivudine plus boosted darunavir in the clinical setting.

Dolutegravir and rilpivirine for the maintenance treatment of virologically suppressed HIV-1 infection.

INTRODUCTION: Triple combinations of antiretroviral therapy (ART) drugs are the standard treatment for human immunodeficiency virus (HIV) infection, but the challenges include long-term side effects, high costs, and adherence. The recent advent of potent and well-tolerated ART has renewed the interest for newer ART strategies. A dual regimen with the combination of dolutegravir (DTG) and rilpivirine (RPV), two well-tolerated, metabolic-friendly, and potent drugs could offer additional benefits. Areas covered: A review of recent randomized trials and observational cohorts concerning the use of a dual therapy with DTG plus RPV as a switching strategy in patients with viral suppression. Expert commentary: Currently, data of more of 900 patients switched to this dual regimen are available. This combination shows a high rate of virological suppression, above 90% at 48 weeks, few discontinuations due to adverse events, improvement in bone and kidney parameters for patients discontinuing tenofovir disoproxil fumarate, lack of loss of the inflammatory control achieved with triple therapy, and a neutral effect on lipid parameters. Thus, for the first time, a dual regimen without protease inhibitors is effective, avoiding metabolic side effects and drug interactions. Longer follow-up is needed, but this dual regimen appears as a promising strategy for aging HIV-infected patients.

Safe use of pegylated interferon/ribavirin in hepatitis C virus cirrhotic patients with hypersplenism after partial splenic embolization.

BACKGROUND AND AIMS: Partial splenic embolization (PSE) is a non-surgical alternative for the treatment of hypersplenism. Thrombocytopenia precludes the use of pegylated interferon (peg-IFN) and ribavirin in cirrhotic patients with hepatitis C virus (HCV). We aimed to evaluate the role of PSE as a procedure allowing combined HCV therapy in this setting. METHODS: A retrospective analysis of the safety and rate of sustained virological response (SVR) after a full-dose course of peg-IFN plus ribavirin in eight HCV cirrhotic patients with severe hypersplenism undergoing PSE at a tertiary centre in Madrid, Spain, from May 2002 to August 2004. RESULTS: Six patients (75%) were in Child-Pugh class B (median score 7). PSE significantly improved the mean platelet (P = 0.012), leucocyte (P = 0.017) and haemoglobin (P = 0.035) levels, and prothrombin activity (P = 0.012). After a mean of 20 weeks after PSE all patients started weight-adjusted ribavirin plus peg-IFN-alpha2b (n = 6) or 180 microg/week of peg-IFN-alpha2a (n = 2). Six subjects (75%) completed therapy with no peg-IFN dose reductions; the dose of ribavirin was reduced in two patients reaching haemoglobin levels of less than 10 g/dl (one also received erythropoietin and granulocyte colony-stimulating factor because of neutrophil counts < 300 cells/microl). Three patients (38%) achieved SVR. Portal vein thrombosis was observed in 50% of patients, but did not preclude antiviral therapy. The pathogenic mechanism was multifactorial. It was successfully managed with anticoagulant therapy in two cases. CONCLUSIONS: PSE allowed the safe use of peg-IFN plus ribavirin in HCV cirrhotic patients with severe cytopenias who otherwise would never have been treated. The rate of SVR was 38%.

Effect of treatment with efavirenz on neuropsychiatric adverse events of interferon in HIV/HCV-coinfected patients.

BACKGROUND: Mood disorders and other neuropsychiatric disorders are common adverse events limiting tolerability of alpha-interferon (IFN) therapy for hepatitis C virus (HCV). Because efavirenz (EFV) frequently produces neuropsychiatric side effects, we studied the effect of EFV in the incidence of these side effects in HIV/HCV patients receiving IFN. METHODS: Prospective cohort of HIV/HCV patients receiving IFN and ribavirin. Adverse events and concomitant medications were systematically recorded once monthly. RESULTS: Among 266 HIV/HCV patients starting a course of IFN (91% pegylated IFN) plus ribavirin, 53 (20%) received concomitant EFV and 213 (80%) did not. Most EFV patients (92%) were already on EFV before starting IFN (mean 26 months). Neuropsychiatric side effects were frequent, without significant differences between both groups (79% vs 65%, P = 0.051), and only 10 patients discontinued IFN. Mood disorders were reported more frequently in EFV patients (36% vs 23%, P = 0.046), but antidepressant therapy use was similar in both groups. The incidence of anxiety, insomnia, irritability, headache or prescription of anxiolytics or hypnotics was similar. CONCLUSIONS: Neuropsychiatric adverse events are common in HIV/HCV patients receiving IFN, usually mild or moderate. EFV may favor symptoms of mood disorders, although it was not related to an increased risk of significant depression requiring specific treatment.