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Additional file 1. Description of study questionnaire.

Macrophages play important roles during HIV-infection, reflected by changes in macrophage-activation biomarker sCD163. Here, we present data on the novel macrophage-activation biomarker soluble mannose receptor/CD206 (sMR/sCD206) in HIV-infection.We investigated sCD206 blood levels at baseline and follow-up with/without ART, in 212 patients with HIV-1, HIV-2, or dual infection.At baseline, there was no difference in sCD206 level between HIV-types, and sCD206 was unchanged at follow-up without ART. However, contrary to sCD163, sCD206 levels decreased significantly for both HIV-1 and HIV-2, but not for HIV-1/2 patients, during ART. Further investigations are needed to establish sCD206 as biomarker in HIV-infection.

OBJECTIVES: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark.MATERIALS AND METHODS: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause.RESULTS: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91).CONCLUSIONS: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.

Background: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection.Methods: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression.Results: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively (P < .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively.Conclusions: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.

People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was undetectable HCV RNA (CONCLUSION: Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor-containing therapy. This article is protected by copyright. All rights reserved.

Background:CNS infection caused by Actinomyces spp. is rare and the subtype Actinomyces meyeri even rarer. Risk factors include periodontal disease and alcohol overuse. We present a case report of a 54-year-old female with dental and lung foci. Case history:A female was hospitalised with tonic-clonic convulsions. She reported a week of headaches, dizziness, fever, respiratory chest pain, and productive cough, following six months of night sweats and an unintended weight loss of 7-8 kg. She appeared dyspnoeic, and fatigued, with a temperature of 37.7°C, leucocytosis, thrombocytosis, and CRP at 68. Lobar pneumonia was suspected and penicillin treatment initiated. Chest x-ray showed a pulmonary nodule; CT-scan of chest and abdomen without tumour-suspicion showed bilateral basal atelectasis. Tonic-clonic seizures were observed. CT-cerebrum revealed a tumour in the left frontotemporal region with surrounding oedema. By MRI an abscess was suspected and the patient was transferred to the department of neurosurgery, where drainage was performed. Microscopy revealed gram-positive cocci and gram-negative rods and iv. treatment with ceftriaxone 4g x 1 and metronidazole 1g x 1 was commenced. Pus cultures showed Prevotella spp. and A. meyeri and the initial treatment was changed to penicillin G 5 MIU x 4 and metronidazole 500 mg x 3 for four weeks followed by oral amoxicillin 500 mg x 3 for three months. The abscess regressed on this treatment and there were no CNS related symptoms at three months follow-up. The source of infection was most likely periodontitis with spread to the lungs from aspiration or oropharyngeal secretion into the respiratory tract, alternatively from haematogenous spread. Conclusions:We report of the successful treatment of a cerebral abscess caused by A. meyeri with narrow spectrum antibiotics. The optimal treatment of A. meyeri CNS infection has not yet been established – case reports are important in reaching this goal.

The members of the Bissau HIV cohort study group are: Amabelia Rodrigues, David da Silva, Zacarias da Silva, Candida Medina, Ines Oliviera-Souto, Lars ∅stergaard, Alex Laursen, Morten Sodemann, Peter Aaby, Anders Fomsgaard, Christian Erikstrup, Jesper Eugen-Olsen and Christian Wejse (chair). Background: Co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) may lead to accelerated hepatic disease progression with higher rates of liver cirrhosis and liver-related mortality compared with HBV mono-infection. Co or super-infection with hepatitis Delta virus (HDV) may worsen the liver disease and complicate treatment possibilities. Methods: In this cross-sectional study we included HIV-infected individuals who had a routine blood analysis performed at an HIV clinic in Bissau, Guinea-Bissau between the 28th of April and 30th of September 2011. All patients were interviewed, had a clinical exam performed and had a blood sample stored. The patients' samples were tested for HBV and HDV serology, and HBV/HDV viral loads were analyzed using in-house real-time PCR methods. Results: In total, 576 patients (417 HIV-1, 104 HIV-2 and 55 HIV-1/2) were included in this study. Ninety-four (16.3%) patients were HBsAg positive of whom 16 (17.0%) were HBeAg positive. In multivariable logistic regression analysis, CD4 cell count

As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated 3 rapid tests for discrimination between HIV-1, HIV-2, and dual infections among 219 patients from Guinea-Bissau by comparing with the gold standard (INNO-LIA). Genie III HIV-1/HIV-2 was the best performer with regard to discriminatory capacity (agreement 91.8%), followed by Immunoflow HIV1-HIV2 (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation.

Endothelial dysfunction and inflammation have been demonstrated to be markers of cardiovascular risk. We investigated the effects of HIV infection per se and the antiretroviral treatment prescribed on the levels of risk factors of cardiovascular disease.

Background: Decisions about when to start anantiretroviral therapy (ART) are normally based on CD4cell counts and viral load (VL). However, thesemeasurements require equipment beyond the capacityof most laboratories in low-income and middle-incomesettings. Thus, there is an urgent need to identify andtest simple markers to guide the optimal time forstarting and for monitoring the effect of ART indeveloping countries.Objectives: (1) To evaluate anthropometricmeasurements and measurement of plasma-solubleform of the urokinase plasminogen activator receptor(suPAR) levels as potential risk factors for earlymortality among HIV-infected patients; (2) to assesswhether these markers could help identify patients towhom ART should be prioritised and (3) to determineif these markers may add information to CD4 cell countwhen VL is not available.Design: An observational study.Setting: The largest ART centre in Bissau, Guinea-Bissau.Participants: 1083 ART-naïve HIV-infected patients.Outcome measures: Associations between baselineanthropometric measurements, CD4 cell counts,plasma suPAR levels and survival were examined usingCox proportional hazards models.Results: Low body mass index (BMI≤18.5 kg/m2),low mid-upper-arm-circumference (MUAC≤250 mm),low CD4 cell count (≤350 cells/μl) and high suPARplasma levels (>5.3 ng/ml) were independentpredictors of death. Furthermore, mortality amongpatients with low CD4 cell count, low MUAC orlow BMI was concentrated in the highest suPARquartile.Conclusions: Irrespective of ART initiation andbaseline CD4 count, MUAC and suPAR plasma levelswere independent predictors of early mortality inthis urban cohort. These markers could be useful inidentifying patients at the highest risk of short-termmortality and may aid triage for ART when CD4 cellcount is not available or when there is shortness ofantiretroviral drugs. BACKGROUND: Decisions about when to start an antiretroviral therapy (ART) are normally based on CD4 cell counts and viral load (VL). However, these measurements require equipment beyond the capacity of most laboratories in low-income and middle-income settings. Thus, there is an urgent need to identify and test simple markers to guide the optimal time for starting and for monitoring the effect of ART in developing countries. OBJECTIVES: (1) To evaluate anthropometric measurements and measurement of plasma-soluble form of the urokinase plasminogen activator receptor (suPAR) levels as potential risk factors for early mortality among HIV-infected patients; (2) to assess whether these markers could help identify patients to whom ART should be prioritised and (3) to determine if these markers may add information to CD4 cell count when VL is not available. DESIGN: An observational study. SETTING: The largest ART centre in Bissau, Guinea-Bissau. PARTICIPANTS: 1083 ART-naïve HIV-infected patients. OUTCOME MEASURES: Associations between baseline anthropometric measurements, CD4 cell counts, plasma suPAR levels and survival were examined using Cox proportional hazards models. RESULTS: Low body mass index (BMI≤18.5 kg/m(2)), low mid-upper-arm-circumference (MUAC≤250 mm), low CD4 cell count (≤350 cells/μl) and high suPAR plasma levels (>5.3 ng/ml) were independent predictors of death. Furthermore, mortality among patients with low CD4 cell count, low MUAC or low BMI was concentrated in the highest suPAR quartile. CONCLUSIONS: Irrespective of ART initiation and baseline CD4 count, MUAC and suPAR plasma levels were independent predictors of early mortality in this urban cohort. These markers could be useful in identifying patients at the highest risk of short-term mortality and may aid triage for ART when CD4 cell count is not available or when there is shortness of antiretroviral drugs.

The Danish Society of Infectious Diseases and Danish Society of Gastroenterology and Hepatology set up a committee in 2007 to produce national guidelines for treatment of viral hepatitis B and C. The 2011 version of the guidelines have been endorsed by the scientific societies and are presented below. Annual updates will be available at the websites of the societies. As this present English version has been written six months after the Danish 2011 version, it contains minor changes that will be integrated in the Danish 2012 version, available at the end this year. Epidemiology: Viral hepatitis is not common in Denmark. The prevalence has not been determined by national surveys, but it is estimated that 10,000-15,000 patients are chronically infected with hepatitis B and 15,000-20,000 with chronic hepatitis C. The majority of patients with HBV infection in Denmark are emigrants from high endemic countries, probably infected at birth or early childhood in their country of origin, while the majority of patients with HCV infection have been infected by drug use. For both groups it is estimated that only half of the patients have been diagnosed, of whom only 20% attends specialized care for their chronic viral hepatitis. Clinical care: According to the Danish National Board of Health, patients with chronic viral hepatitis should be followed with regular intervals, at clinics specialized in either infectious diseases or gastroenterology/hepatology. The primary aim is to identify patients with significant liver disease to initiate treatment in order to prevent development of cirrhosis and death. This is primarily done by liver biopsy, but screening for fibrosis with non-invasive methods such as elastography may be sufficient in some patients. Patients with established cirrhosis should enter screening programs for complications such as esophageal varices and hepatocellular carcinoma.