Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy

Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recru

Hepatitis C in Hemophilia

Hepatitis is a major cause of morbidity and mortality in patients with hemophilia. In our study with a follow-up of 35 years, we found that the risk for end-stage liver disease (liver failure, hepatocellular carcinoma, liver-related death) was 12% for HIV negative, and 35% for HIV coinfected patients. Although a significant proportion of hemophilia patients is at risk for long-term complications of hepatitis, many patients still have not been treated. In the Dutch hemophilia population, approximately 30-40% were not treated mainly due to fear of side effects, lack of clinical symptoms, and expected low efficacy of treatment. However, health-related quality of life was reduced in hemophilia patients with chronic hepatitis C. Thus providing an additional argument in favor of treatment, as health-related quality of life will improve after successful treatment for hepatitis C. Liver biopsies are rarely performed in hemophilia patients because of risk of bleeding, and high costs of clotting factor replacement. In order to assess liver fibrosis in the hemophilic population and identify patients eligible for antiviral therapy, we were the first to use a new, non-invasive device: the Fibroscan®. With this new technique we found an unexpected high proportion of patients with severe fibrosis or cirrhosis of approximately 35%. Many patients had significant liver damage that would not have been detected with the conventional methods like laboratory tests and ultrasonography. Based on the results of the Fibroscan® examination, approximately 25% of patients started antiviral therapy within three months. The majority of these patients had postponed antiviral therapy for years despite therapy had frequently been offered. These results indicate that the Fibroscan® may play an important role in persuading patients with significant fibrosis to start therapy. Furthermore, this technique may be used to follow patients in order to assess progression of fibrosis and determine prognosis. Conflicting data exist about the efficacy of IFN-based therapy in the hemophilic population. For many years, it was thought that patients with hemophilia would respond worse to IFN-based therapy than patients in the general population. Patients with hemophilia are often infected with HCV genotype 1, are predominantly male, have long-lasting infection, and have often high levels of viraemia. However, in our review of IFN-based therapies in the hemophilic population responses were similar to that seen in the general population. This was also corroborated in our pilot study of patients who were treated with Pegylated IFN combined with ribavirin. The sustained virological response for HIV negative and treatment naïve patients was 70%. This high response may be due to the high compliance to therapy in this population. The direct responses to antiviral therapy are precisely defined, but what are the long-term effects of this therapy? In a cohort study of approximately 300 patients, we found that all patients who achieved a sustained response after IFN-based therapy remained HCV RNA negative up to 15 years after treatment. Furthermore, none of the successfully treated patients developed liver failure or hepatocellular carcinoma. This was in contrast with patients who failed to eradicate HCV: the risk for developing end-stage liver disease was approximately 13%. In conclusion, these findings indicate that successful therapy postpones or may even prevent long-term complications of chronic hepatitis C during the first 10-15 years after therapy. However, longer follow-up is required to assess whether this favorable effect is sustained over the next decades

An 86-year-old man with acute abdominal pain

An 86-year-old man presented with severe pain in the upper abdomen along with fever. On physical examination, we found an arterial blood pressure of 84/43 mm Hg, a heart rate of 80 bpm and a temperature of 38.3°C. The abdomen was painful and peristalsis was absent. Empiric antibiotic therapy for sepsis was started with amoxicillin/clavulanate and gentamicin. CT scan of the abdomen revealed an emphysematous cholecystitis. Percutaneous ultrasound-guided cholecystostomy was applied. Bile cultures revealed Clostridium perfringens. Emphysematous cholecystitis is a life-threatening form of acute cholecystitis that occurs as a consequence of ischaemic injury to the gallbladder, followed by translocation of gas-forming bacteria (ie, C. perfringens, Escherichia coli, Klebsiella and Streptococci). The mortality associated with emphysematous cholecystitis is higher than in non-emphysematous cholecystitis (15% vs 4%). Therefore, early diagnosis with radiological imaging is of vital importance.2016 BMJ Publishing Group Ltd

Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study

The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes.We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-na?ve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight (<18.5), normal (18.5-25), overweight (25-30) and obese (> 30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year.A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and 125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18 (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction > 0.05).Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI.? 2015 British HIV Association

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naive HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

ObjectivesLamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients.MethodsAn observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression &lt;400 copies/mL, and time to treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models.ResultsA total of 1582 ART-naive HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements &lt;400 copies/mL within 48 weeks (HR 0.94; 95% CI 0.78-1.16) and the time to treatment failure after suppression &lt;400 copies/mL (HR 0.94; 95% CI 0.36-2.50) were not significantly influenced by the use of 3TC in TDF/PI-containing cART.ConclusionsThe virological responses were not significantly different in treatment-naive HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI.</p

Intentional overdose of dolutegravir/abacavir/lamivudine (Triumeq) in a 26-year-old man

Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless. As Triumeq will be used on a regular basis as treatment for patients with HIV-1 infection, these intoxications are expected to be encountered more often