Indication for treatment and severity of disease in treatment-naive patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The prevalence of chronic hepatitis B virus (HBV) infection in Europe is poorly defined. Data on the proportion of patients eligible for therapy are lacking but are crucial to meet WHO elimination goals. The aims of our study were to provide an estimate of the need for antiviral treatment and to assess the prevalence of advanced liver disease in treatment-naive, chronic HBV-infected patients. PATIENTS AND METHODS: We performed a retrospective, cross-sectional analysis of all treatment-naive HBV-infected patients. Baseline clinical assessments included sociodemographic data, hepatitis B-specific analyses, and liver stiffness measurement (LSM). RESULTS: Between 2010 and 2017, 465 patients with chronic HBV infection were referred, with 301 (64.7%) being eligible for our analysis. Overall, 40% were female, and the mean age was 39.3±13.1 years. Moreover, 61% of patients were born outside Europe, predominantly in the Asia-Pacific region. The median HBV viral load was 1630 IU/ml (interquartile range: 240-35 000 IU/ml), 145 (48.2%) patients had an HBV viral load above 2000 IU/ml, and 14.3% were HBeAg positive.Median LSM was 5.2 kPa (interquartile range: 4.2-6.6 kPa). LSM indicating clinically significant fibrosis (≥F2) was found in 96/271 (35.0%) patients, including 20/271 (7.4%) patients with suspected advanced fibrosis/cirrhosis. Overall, 26% of patients met EASL 2017 treatment criteria. CONCLUSION: In HBV-infected patients referred to one of the largest ID clinics in Berlin, only 26% met EASL treatment criteria and 7% had suspected cirrhosis at presentation. Only in 4% of all patients, a treatment indication could not be determined by a noninvasive approach.

Evaluation of a temporary vaccination recommendation in response to an outbreak of invasive meningococcal serogroup C disease in men who have sex with men in Berlin, 2013-2014.

Meningococcal serogroup C (MenC) vaccination of men who have sex with men (MSM) was temporarily recommended to control an outbreak of invasive MenC disease among MSM in Berlin in 2012-2013. Vaccination was offered to HIV-infected MSM free of charge; others had to request reimbursement or pay out of pocket. We aimed to assess (i) awareness and acceptance of this recommendation through an online survey of MSM, (ii) implementation through a survey of primary care physicians and analysis of vaccine prescriptions, and (iii) impact through analysis of notified cases. Among online survey respondents, 60% were aware of the recommendation. Of these, 39% had obtained vaccination (70% of HIV-infected, 13% of HIV-negative/non-tested MSM). Awareness of recommendation and vaccination were positively associated with HIV infection, primary care physicians' awareness of respondents' sexual orientation, and exposure to multiple information sources. Most (26/30) physicians informed clients about the recommendation. Physicians considered concerns regarding reimbursement, vaccine safety and lack of perceived disease risk as primary barriers. After the recommendation, no further outbreak-related cases occurred. To reach and motivate target groups, communication of a new outbreak-related vaccination recommendation should address potential concerns through as many information channels as possible and direct reimbursement of costs should be enabled.

Acute hepatitis C virus (HCV) infection in the setting of HIV coinfection: a single-centre 10-year follow-up.

INTRODUCTION: Acute hepatitis C virus (HCV) infection has emerged as a major cause of morbidity in the HIV-infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV-infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long-term analysis on patients with acute HCV. METHODS: Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT) criteria were included in the database at their date of HCV diagnosis and followed-up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®). A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a) liver-related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b) non-liver-related: death, myocardial infarction, AIDS-defining event, psychiatric hospitalisation. RESULTS: A total of 207 cases of acute HCV infection in HIV-infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78%) were on antiretroviral treatment, and the median CD4 cell count was 593/mm(3) (IQR 443-749). At HCV diagnosis, the highest median alanine aminotransferase (ALT) level was 408 IU/mL (159-871), the HCV viral load was 800,000 IU/mL (45x103-2.8x106). 22 cases (11%) cleared their infection spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were followed-up over an interval of 806 patient-years. The median liver stiffness was 5.3 kPa (4-7) after a median interval of 34 months. 33 patients developed significant fibrosis, and 11 patients (6%) developed cirrhosis. Nine (5%) patients died during follow-up, and 11 developed non-liver-related endpoints. All but one deceased patients had interferon-based treatment. CONCLUSIONS: Severe hepatic disease and death rarely occurs in a highly treated HCV population. As interferon-based treatment may induce side effects, it is from now on justified to await new HCV treatment options.

New dolutegravir resistance pattern identified in a patient failing antiretroviral therapy.

INTRODUCTION: The most recently approved antiretroviral, the integrase inhibitor dolutegravir (DTG), is described to be a very potent drug with a unique resistance profile, but a certain degree of cross-resistance to RAL or EVG induced drug resistance, which is mediated mainly by integrase mutations at positions 140 and 148. The impact of a single N155H mutation to DTG resistance is described to be minor. However, there is only rare data available about the impact of N155H in the context of secondary site integrase mutations. Here, we present a case of virological failure in a DTG treated patient based on N155H mutation background. METHODS: Therapy monitoring of an HIV-HCV co-infected patient harbouring already an omni-drug-class resistant HIV-1 in consequence of more than 20 years ART history. Drug susceptibility testing was performed by RT-PCR from plasma and subsequent Sanger sequencing. Tropism testing was done from proviral DNA with FPR cut-offs according to the German recommendations. RESULTS: In 2013, the patient harbouring a virus with high level resistance to all RTI and PI received a regimen containing FTC, TDF, DRV/r, RPV, T20, and RAL to handle a viral load of 5000 RNA copies/mL, but never achieved fully suppressed viral load. In June 2013, after S119R, N155H and E157Q mutations in viral integrase were detected, the patient received DTG, and RAL was stopped. One month later, when viral load was undetectable for the first time since 2007, ART was de-escalated by removing T20. Since February 2014, low-level viral load was re-detectable. Two new mutations T97A and S147G in the integrase and no other new resistance associated mutations in protease and reverse transcriptase in comparison to the sample analyzed in June 2013 were detected. CONCLUSIONS: Highly resistant HIV-1 strains have been a common problem in the past. Their frequencies were pushed back by highly potent ART, but the virus is still able to become resistant against all available antiretrovirals at once. The here documented strain became resistant to DTG without carrying mutations at the described positions 140 and 148, but in the context of integrase N155H. Since N155H alone is described not to contribute sufficient resistance to DTG, there seems to be a need to re-check viruses with N155H plus minor mutations (like T97A, S119R, S147G and E157Q) potentially contributing to DTG resistance.