Publications by authors named "Christoph Boesecke"

92 Publications

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART).

EClinicalMedicine 2021 Oct 5;40:101116. Epub 2021 Sep 5.

Department of Internal Medicine I, University Hospital Frankfurt, Germany.

Background: De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD.

Methods: This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates.

Findings: 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m (OR: 4·238, 95% CI: 2·078-8·938; < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362-10·899); < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370-4·048;  = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315-24·981; < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12-0·64;  = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101-0·945;  = 0·04).

Interpretation: Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis.

Funding: There was no additional funding received for this project. All funders mentioned in the 'declaration of interests' section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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http://dx.doi.org/10.1016/j.eclinm.2021.101116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427211PMC
October 2021

Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance.

AIDS Res Ther 2021 09 8;18(1):58. Epub 2021 Sep 8.

School of Medicine, University Hospital Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Objective: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.

Design: Post hoc analysis of a randomized trial.

Methods: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).

Results: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.

Conclusions: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.

Trial Registration: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE .
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http://dx.doi.org/10.1186/s12981-021-00384-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425038PMC
September 2021

Factors associated with testing for HIV and hepatitis C among behaviorally vulnerable men in Germany: a cross-sectional analysis upon enrollment into an observational cohort.

AIDS Res Ther 2021 08 16;18(1):52. Epub 2021 Aug 16.

Institute of Virology, Medical Faculty, University Bonn, Bonn, Germany.

Background: HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM.

Methods: From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months.

Results: Among 1017 participants with median age 33 (interquartile range 28-39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing.

Conclusion: Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.
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http://dx.doi.org/10.1186/s12981-021-00378-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365908PMC
August 2021

CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies.

Clin Infect Dis 2021 07;73(1):50-59

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.

Background: A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.

Methods: PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.

Results: We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL).

Conclusions: Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
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http://dx.doi.org/10.1093/cid/ciaa1137DOI Listing
July 2021

SARS-CoV-2 seroconversions and chains of infection in healthcare professionals in a German maximum care provider (The CoSHeP study).

Infection 2021 Oct 18;49(5):1039-1043. Epub 2021 Jun 18.

Department of Medicine I, Bonn University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany.

Introduction: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants.

Methods: Single-center, longitudinal observational study investigating rate of SARS-CoV-2 IgG seroconversion in HP at 2 time-points. SARS-CoV-2 IgG was measured with Roche Elecsys Anti-SARS-CoV-2 assay.

Results: Overall, 150 HP were included. Median age was 35 (range: 19-68). Main operational areas were intensive care unit (53%, n = 80), emergency room (31%, n = 46), and infectious disease department (16%, n = 24). SARS-CoV-2-IgG was detected in 5 participants (3%) at inclusion in May/June 2020, and in another 11 participants at follow-up (December 2020/ January 2021). Of the 16 seropositive participants, 14 had already known their SARS-CoV-2 infection because they had performed a PCR-test previously triggered by symptoms. Trailing chains of infection by self-assessment, 31% (n = 5) of infections were acquired through private contacts, 25% (n = 4) most likely through semi-private contacts during work. 13% (n = 2) were assumed to result through contact with contagious patients, further trailing was unsuccessful in 31% (n = 5). All five participants positive for SARS-CoV-2 IgG at inclusion remained positive with a median of 7 months after infection.

Discussion: Frontline HP caring for hospitalized patients with COVID-19 are at higher risk of SARS-CoV-2 infections. Noteworthy, based upon identified chains of infection most of the infections were acquired in private environment and semi-private contacts during work. The low rate of infection through infectious patients reveals that professional hygiene standards are effective in preventing SARS-CoV-2 infections in HP. Persisting SARS-CoV-2-IgG might indicate longer lasting immunity supporting prioritization of negative HP for vaccination.
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http://dx.doi.org/10.1007/s15010-021-01641-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211969PMC
October 2021

Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal.

Health Sci Rep 2021 Jun 4;4(2):e290. Epub 2021 Jun 4.

First Department of Medicine University Medical Centre of the Johannes Gutenberg-University Mainz Germany.

Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV-related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct-acting antivirals-highly effective and well-tolerated therapies for HCV-many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country-specific barriers and challenges, particularly in at-risk populations such as people who inject drugs or men who have sex with men, has the potential to create tailored programs and strategies to increase access to screening or treatment and engage at-risk populations. This review aims to report the current steps toward HCV elimination in Germany, the country-specific barriers and challenges that will potentially prevent reaching the 2030 HCV elimination goal and describe good practice examples to overcome these barriers.
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http://dx.doi.org/10.1002/hsr2.290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177898PMC
June 2021

Cardiac MRI in Suspected Acute COVID-19 Myocarditis.

Radiol Cardiothorac Imaging 2021 Apr 4;3(2):e200628. Epub 2021 Mar 4.

Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (J.A.L., A.I., N.M., M.R., A.F., D.D., U.A.); Quantitative Imaging Lab Bonn (QILaB) (J.A.L., A.I., N.M., M.R., A.F., D.D.); Department of Internal Medicine II - Cardiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (C.O., S.Z.); Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (M.M., S.S., C.B., C.P.S., J.N.); Department of Internal Medicine III-Oncology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (A.H.); Department of Anesthesiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (M.V.); Department of Cardiac Surgery, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany (G.D.D.).

COVID-19; coronavirus; myocarditis; cardiac MRI; T1 mapping; T2 mapping.
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http://dx.doi.org/10.1148/ryct.2021200628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098091PMC
April 2021

Health-related quality-of-life in people living with HIV after switching to dual therapy with ritonavir-boosted darunavir + dolutegravir: a DUALIS sub-study.

AIDS Care 2021 Apr 25:1-10. Epub 2021 Apr 25.

Department of Psychosomatic Medicine and Psychotherapy, Klinik Barmelweid AG, Barmelweid, Switzerland.

The DUALIS study demonstrated efficacy and safety of switching to dolutegravir plus ritonavir-boosted darunavir (DRV/r) (2DR) as compared to standard-of-care-therapy with two nucleoside reverse transcriptase inhibitors + DRV/r (3DR) in pretreated people living with HIV (PLWH), 48 weeks after switching. This DUALIS sub-study investigates health-related-quality-of-life (HrQoL) in this study-population. The Hospital Anxiety and Depression Scale (HADS) and the Medical Outcome Survey-HIV (MOS-HIV) were used assessing anxiety and depression symptoms, respectively HrQoL. Data were collected at baseline, 4, 24, and 48 weeks after randomization. Outcome scores were dichotomized and used as criteria in longitudinal models identifying differential developments. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed as main measures of effects. ORs<1 indicate better results for HADS, and worse for MOS-HIV scores in the 2DR compared to 3DR group. In total, 263 subjects were randomized and treated (2DR n=131, 3DR n=132; median age 48 years). Significant different progressions could only be found for HADS-Depression scores (OR=.87, 95% CI: .78, .98, =.02). While HADS-Depression scores decreased in the 2DR group, they increased in 3DR group. This sub-study showed no disadvantages regarding HrQoL in PLWH after switching to DTG+DRV/r. Considering lifelong requirements for antiretroviral medication, close attention to HrQL is required.
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http://dx.doi.org/10.1080/09540121.2021.1916873DOI Listing
April 2021

Communicable and noncommunicable liver disease in HIV.

Curr Opin HIV AIDS 2021 05;16(3):152-155

Department of Medicine I, University Hospital Bonn, Bonn, Germany.

Purpose Of Review: The aim of this study was to highlight the profound changes in the cause in chronic liver disease in HIV-infected individuals.

Recent Findings: Hepatitis C virus (HCV) has been transformed into a curable viral infection by highly effective treatments. This has resulted in elimination of chronic hepatitis C in HIV-coinfected individuals at least in resource-rich settings. Hepatitis B virus (HBV) has become a chronic infection, which is easily controlled by long-term therapy with HBV polymerase inhibitors. As a result, nonalcoholic steatohepatitis (NASH) has gained clinical importance. The obesity epidemic in the general population has also included people with HIV and weight gain has been associated with some newer antiretroviral drugs, such as HIV integrase inhibitors and tenofovir alafenamide fumarate. Medical treatment for obesity is a focus of intense research efforts, but currently, the only convincing therapeutic option in morbidly obese patients is bariatric surgery, which can also improve liver outcomes. The wider use of this approach has included HIV-infected individuals allowing to assess at least the safety aspects of bariatric surgery in this special population.

Summary: The shift from communicable to noncommunicable liver disease is changing the clinical practice in HIV-infected individuals. Research activities are focusing more on treatment of NASH and obesity, although a curative therapy for HBV infection would have a great clinical impact.
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http://dx.doi.org/10.1097/COH.0000000000000675DOI Listing
May 2021

Communicable and noncommunicable liver disease in HIV.

Curr Opin HIV AIDS 2021 05;16(3):152-155

Department of Medicine I, University Hospital Bonn, Bonn, Germany.

Purpose Of Review: The aim of this study was to highlight the profound changes in the cause in chronic liver disease in HIV-infected individuals.

Recent Findings: Hepatitis C virus (HCV) has been transformed into a curable viral infection by highly effective treatments. This has resulted in elimination of chronic hepatitis C in HIV-coinfected individuals at least in resource-rich settings. Hepatitis B virus (HBV) has become a chronic infection, which is easily controlled by long-term therapy with HBV polymerase inhibitors. As a result, nonalcoholic steatohepatitis (NASH) has gained clinical importance. The obesity epidemic in the general population has also included people with HIV and weight gain has been associated with some newer antiretroviral drugs, such as HIV integrase inhibitors and tenofovir alafenamide fumarate. Medical treatment for obesity is a focus of intense research efforts, but currently, the only convincing therapeutic option in morbidly obese patients is bariatric surgery, which can also improve liver outcomes. The wider use of this approach has included HIV-infected individuals allowing to assess at least the safety aspects of bariatric surgery in this special population.

Summary: The shift from communicable to noncommunicable liver disease is changing the clinical practice in HIV-infected individuals. Research activities are focusing more on treatment of NASH and obesity, although a curative therapy for HBV infection would have a great clinical impact.
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http://dx.doi.org/10.1097/COH.0000000000000675DOI Listing
May 2021

Obstacles to HBV functional cure: Late presentation in HIV and its impact on HBV seroconversion in HIV/HBV coinfection.

Liver Int 2020 12 14;40(12):2978-2981. Epub 2020 Oct 14.

Bonn University Hospital, Bonn, Germany.

Several cohorts have shown that long-term tenofovir-containing combination antiretroviral therapy (cART) leads to higher HBsAg seroclearance rates in HIV/HBV coinfected patients vs HBV-monoinfected patients under tenofovir disoproxil fumarate (TDF)-based therapy. We have analysed data on determinants of HBsAg loss in a retrospective multicentric cohort of 359 HIV/HBV coinfected patients. Median CD4 T-cell count at baseline was 359/ul (321-404), CDC stage was C in 20% (n = 70). Most patients (68%) were ART-naïve when TDF- or tenofovir alafenamide (TAF)-containing cART was initiated (baseline). After a median follow-up of 11 years HBsAg loss had occurred in 66/359 (18%) patients. However, patients with stage CDC C (P ≤ .001), lower CD4 gain (P = .043) and not receiving TDF/FTC (P = .008) were less likely to lose HBsAg. Long-term TDF-containing cART appears to achieve higher rates of HBsAg seroclearance compared to published data for HBV monoinfected subjects. However, late presentation for HIV and poor immune recovery significantly impair HBV seroconversion rates.
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http://dx.doi.org/10.1111/liv.14684DOI Listing
December 2020

Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study.

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa356. Epub 2020 Aug 13.

Bonn University Hospital, Bonn, Germany.

Background: Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH).

Methods: DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA <50 copies/mL taking 2NRTI + bDRV (3DR) for ≥24 weeks (1 accepted blip <200 copies/mL) were randomized to either switch to DTG 50 mg + DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR. The primary end point (PE) was the proportion of HIV RNA <50 copies/mL at week (W) 48. Change in NRTI backbone was not classified as failure. The estimated sample size for PE analysis was 292; the noninferiority margin was ≤-10.0%.

Results: In total, 263 subjects were randomized and treated (2DR n = 131, 3DR n = 132; 90.1% male; 89.7% Caucasian; median age [interquartile range], 48 [39-54] years). At W48, 86.3% (n = 113/131) of the 2DR subject and 87.9% (n = 116/132) of the 3DR subjects had HIV RNA <50 copies/mL; the difference between arms was -1.6% (95.48% CI, based on the adjusted alpha level accounting for the interim analysis at W24, -9.9% to +6.7%; discontinuations due to adverse events: 2DR, 4.6% [n = 6]; 3DR, 0.8% [n = 1]). Kaplan-Meier estimates of confirmed HIV RNA ≥50 copies/mL at W48 were 1.6% (n = 2) in the 2DR and 3.1% (n = 4) in the 3DR group. Development of treatment-emergent resistance was not observed.

Conclusions: Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.
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http://dx.doi.org/10.1093/ofid/ofaa356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491710PMC
September 2020

Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons.

AIDS 2020 08;34(10):1485-1495

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen, Denmark.

Background: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.

Methods: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata.

Results: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.

Conclusion: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.
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http://dx.doi.org/10.1097/QAD.0000000000002570DOI Listing
August 2020

Adequate plasma levels of dolutegravir in combination with ritonavir-boosted darunavir: a pharmacokinetic subgroup analysis of the DUALIS study.

J Antimicrob Chemother 2020 10;75(10):3082-3084

Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Department of Medicine II, Ismaninger Str. 22, 81675 Munich, Germany.

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http://dx.doi.org/10.1093/jac/dkaa234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678892PMC
October 2020

Combination of phosphodiesterase-5-inhibitors and beta blockers improves experimental portal hypertension and erectile dysfunction.

Liver Int 2020 09 22;40(9):2228-2241. Epub 2020 Jul 22.

Department of Internal Medicine I, Hospital of the Goethe University, Frankfurt, Germany.

Background & Aims: Phosphodiesterase-5 inhibitors (PDE-5-I) are used for treatment of erectile dysfunction (ED), which is common in patients with cirrhosis. They may improve portal hypertension (PH), but contradictory data on efficacy and side-effects have been reported. Non-selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE-5-I with NSBB and its impact on PH and ED in experimental cirrhosis.

Methods: ED was assessed in cirrhotic patients (n = 86) using standardized questionnaire. Experimental cirrhosis was induced by bile-duct-ligation or carbon-tetrachloride intoxication in rats. Corpus cavernosum pressure - a surrogate of ED -, as well as systemic and portal haemodynamics, were measured in vivo and in situ after acute administration of udenafil alone or in combination with propranolol. mRNA and protein levels of PDE-5 signalling were analysed using PCR and western Blot.

Results: ED in humans was related to severity of liver disease and to NSBB treatment. PDE-5 was mainly expressed in hepatic stellate cells and upregulated in human and experimental cirrhosis. Propranolol reduced corpus cavernosum pressure in cirrhotic rats and it was restored by udenafil. Even though udenafil treatment improved PH, it led to a reduction of mean arterial pressure. The combination of udenafil and propranolol reduced portal pressure and hepatic resistance without systemic side-effects.

Conclusions: ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE-5-I and NSBB improves ED and PH in experimental cirrhosis.
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http://dx.doi.org/10.1111/liv.14586DOI Listing
September 2020

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005-2017.

Infection 2020 Oct 1;48(5):723-733. Epub 2020 Jul 1.

Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Herderstraße 52-54, 50931, Cologne, Germany.

Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.

Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.

Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR).

Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
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http://dx.doi.org/10.1007/s15010-020-01469-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519003PMC
October 2020

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

Int J Colorectal Dis 2020 Jun 26;35(6):1103-1110. Epub 2020 Mar 26.

Department of Surgery, University Hospital of Bonn, Sigmund-Freud-Str. 25, Bonn, Germany.

Purpose: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality.

Material And Methods: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires.

Results: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032).

Conclusion: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.
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http://dx.doi.org/10.1007/s00384-020-03567-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245587PMC
June 2020

Prediction of Esophageal Varices by Liver Stiffness and Platelets in Persons With Human Immunodeficiency Virus Infection and Compensated Advanced Chronic Liver Disease.

Clin Infect Dis 2020 12;71(11):2810-2817

McGill University Health Centre, Montreal, Quebec, Canada.

Background: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH.

Methods: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/μL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/μL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%.

Results: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/μL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively.

Conclusions: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.
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http://dx.doi.org/10.1093/cid/ciz1181DOI Listing
December 2020

Hepatitis C reinfection with protease inhibitor-resistant hepatitis C virus in an HIV-coinfected MSM.

Liver Int 2020 01 31;40(1):47-50. Epub 2019 Oct 31.

Department of Medicine I, University Hospital Bonn, Bonn, Germany.

There is an ongoing global hepatitis C virus (HCV) epidemic mainly related to high-risk behaviour in persons who inject drugs (PWID) and in HIV-infected men who have sex with men (MSM) which continues to fuel the HCV epidemic. Treatment of HCV infection with direct antiviral therapy (DAA) has been very successful in the last decade. Main obstacles for HCV elimination are HCV reinfections observed in PWID and HIV-infected MSM. We present here an HIV-infected MSM patient who has been reinfected thrice with HCV. The virus which was investigated from his last reinfection episode reveals transmission of a newly acquired HCV protease inhibitor (PI) resistance, despite not having been exposed to HCV-PIs during his last DAA therapy.
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http://dx.doi.org/10.1111/liv.14275DOI Listing
January 2020

Reinfection With the Hepatitis C Virus in Men Who Have Sex With Men After Successful Treatment With Direct-acting Antivirals in Germany: Current Incidence Rates, Compared With Rates During the Interferon Era.

Clin Infect Dis 2020 08;71(5):1248-1254

Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.

Background: Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era.

Methods: Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (using data from the European Acquired Immunodeficiency Syndrome Treatment Network [NEAT]).

Results: Between January 2014 and April 2018, 48 HCV reinfections occurred in 2298 individuals (2%), with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16-1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (py; 95% confidence interval [CI], 1.41-2.48). In a multivariate analysis, the transmission risk in MSM was the only independent risk factor of HCV reinfection (odds ratio, 39.3; 95% CI, 4.57-334.40; P = .001). The incidence rate in MSM was 9.02 (95% CI, 6.48-12.26) per 100 py, compared to 1.14 per 100 py in PWID (95% CI, .56-2.09). The incidence rate for a first HCV reinfection in MSM was similar in the direct-acting antiviral era, compared to the interferon era, with a hazard ratio of 1.05 (95% CI, .64-1.74; P = .831).

Conclusions: HCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.
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http://dx.doi.org/10.1093/cid/ciz949DOI Listing
August 2020

The German National Registry of Primary Immunodeficiencies (2012-2017).

Front Immunol 2019 19;10:1272. Epub 2019 Jul 19.

Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.

The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
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http://dx.doi.org/10.3389/fimmu.2019.01272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659583PMC
October 2020

Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis.

J Infect Dis 2019 10;220(10):1635-1644

Center for Infectiology, Berlin, Germany.

Background: Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin.

Methods: An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM).

Results: Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM.

Discussion: HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.
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http://dx.doi.org/10.1093/infdis/jiz367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360352PMC
October 2019

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART.

PLoS One 2019 11;14(7):e0219526. Epub 2019 Jul 11.

Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.

Background And Aims: Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.

Methods: 116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.

Results: Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.

Conclusion: The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219526PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622522PMC
February 2020

Treatment of acute hepatitis C in HIV coinfection: Is this a chance for achieving microelimination?

United European Gastroenterol J 2019 05 26;7(4):465-466. Epub 2019 Apr 26.

Department of Medicine I, University Hospital Bonn, Bonn, Germany.

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http://dx.doi.org/10.1177/2050640619843735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488798PMC
May 2019

Fibroblast growth factor 21 is independently associated with severe hepatic steatosis in non-obese HIV-infected patients.

Liver Int 2019 08 5;39(8):1514-1520. Epub 2019 Apr 5.

Department of Medicine I, University of Bonn, Bonn, Germany.

Background: Severe hepatic steatosis shows a high prevalence and contributes to morbidity and mortality in human immunodeficiency virus (HIV) infected patients. Known risk factors include obesity, dyslipidaemia and features of metabolic syndrome. Fibroblast growth factor 21 (FGF-21) is involved with hepatic glucose and lipid metabolism. This study aimed to evaluate FGF-21 as a biomarker for severe hepatic steatosis in non-obese HIV-infected patients.

Methods: This is a prospective, cross-sectional, monocentric study including HIV-infected out-patients. Hepatic steatosis was measured via controlled attenuation parameter (CAP) using FibroScan 502 touch (ECHOSENS, France). Severe hepatic steatosis was defined at CAP ≥ 253 dB/m. Peripheral blood samples were collected and plasma was analysed for FGF-21. Demographic and clinical characteristics were collected from patient's health records.

Results: In total, 73 non-obese HIV-monoinfected patients were included in this study. Prevalence of severe hepatic steatosis was 41%. Patients with severe hepatic steatosis showed significantly higher levels of FGF-21. Univariate analysis revealed FGF-21, BMI, hyperlipidaemia, ALT levels and arterial hypertension as significant, while multivariate analysis showed only FGF-21, arterial hypertension and ALT levels as significant independent risk factors for severe hepatic steatosis.

Conclusion: This study presents FGF-21 as an independent and stronger predictor of severe hepatic steatosis than blood lipids in HIV-infected patients. Moreover, arterial hypertension and ALT levels predict severe steatosis even in non-obese HIV-monoinfected patients. Furthermore, this study supports existing metabolic risk factors and expands them to non-obese HIV-infected patients.
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http://dx.doi.org/10.1111/liv.14107DOI Listing
August 2019

Has Increased Rollout of Direct Acting Antiviral Therapy Decreased the Burden of Late Presentation and Advanced Liver Disease in Patients Starting Hepatitis C Virus Therapy in Germany?

J Clin Gastroenterol 2020 02;54(2):192-199

Department of Medicine I, University Hospital Bonn, Bonn.

Goals And Background: International guidelines recommend prioritized treatment initiation in hepatitis C virus (HCV)-infected patients with advanced liver disease. We aimed to evaluate whether the widespread usage of direct acting antivirals (DAAs) has led to a decrease in late presentation for care.

Study: Data derived from the multicenter German Hepatitis C Cohort (GECCO) was analyzed. Treatment naive HCV-infected patients initiating DAA-based treatment between January 2014 and September 2017 were included. Advanced liver disease was defined by aspartate aminotransferase to platelet ratio index score ≥1.5, METAVIR≥F3, or FibroScan ≥9.5 kPa. Period prevalence and risk factors for late presentation were evaluated.

Results: Six hundred fifty-three HCV-monoinfected and 210 HIV/HCV-coinfected patients (mean age, 48.6±12.7 y; 65.5% male) were included. Overall 32.5% of patients had advanced liver disease. In 2014 39.4% of patients presented with advanced liver disease, decreasing to 30.1%, 34.4%, and 26.4% in the years 2015, 2016, and 2017 (P=0.057), respectively. Patients with and without advanced liver disease differed in age (P<0.0001), CD4 ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P<0.001), and time since diagnosis (P=0.007). In the multivariable binary logistic regression analysis GT3, age above 45 years and being diagnosed >2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease.

Conclusions: Overall 32.5% of patients presented with advanced liver disease. We observed a trend toward a lower proportion of patients starting treatment late.GT3, age, years since HCV diagnosis and HCV transmission route were identified as risk factors for presentation with advanced liver disease.
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http://dx.doi.org/10.1097/MCG.0000000000001189DOI Listing
February 2020

Risk factors for remaining liver injury in patients with virological elimination of chronic hepatitis C.

Z Gastroenterol 2019 Feb 12;57(2):139-147. Epub 2019 Feb 12.

Department of Medicine III, University-Hospital Aachen, Aachen, Germany.

Background And Aims:  Disease activity, but also demographics, lifestyle, and comorbidities, may influence alanine aminotransferase (ALT) levels in hepatitis C virus (HCV)-infected patients. Direct-acting antiviral agents (DAA) achieve virological cure in > 90 % of patients, regardless of HCV genotype and fibrosis stage. This allows assessing determinants for ALT levels before and after elimination of HCV.

Methods:  Our prospective cohort included HCV- and HIV/HCV-infected patients treated with DAA at 9 German centers (GECCO cohort). We analyzed all consecutive patients with sustained virological response (SVR) at week 12 (SVR12) and/or 24. Normal ALT was defined as ≤ 35 U/L, regardless of sex.

Results:  At baseline, 1477 out of 1774 patients (83 %) had ALT > 35 U/L, and 297 (17 %) had ALT ≤ 35 U/L. Baseline ALT > 35 U/L was independently associated with male sex, higher body mass index (BMI), liver cirrhosis, and not being on opioid substitution. After SVR, > 80 % of patients normalized ALT, and even patients with low baseline ALT further reduced ALT levels. However, ALT remained > 35 U/L in 15 % (221/1477) after SVR12. By multivariate analysis, ALT > 35 U/L at SVR12 was associated with male sex, higher BMI, liver cirrhosis, baseline ALT, HCV genotype 2, and younger age. Obesity, cirrhosis, and ALT were also independent factors associated with ALT > 15 U/L at SVR12 in patients with normal ALT at baseline.

Conclusions:  Male sex, advanced liver fibrosis, and obesity are main risk factors for the lack of ALT normalization and/or ALT decline after SVR, indicative of fatty liver disease as a relevant comorbidity in hepatitis C.
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http://dx.doi.org/10.1055/a-0752-0514DOI Listing
February 2019

[Opportunistic infections: What's new?]

Dtsch Med Wochenschr 2018 12 3;143(24):1755-1758. Epub 2018 Dec 3.

Klinische Arbeitsgemeinschaft AIDS Deutschland (KAAD), Sektion der Deutschen AIDS-Gesellschaft (DAIG).

Guidelines from 3 clinical societies and peer-reviewed publications have been reviewed for recent changes in the management of opportunistic infections. Trimethoprim and sulfamethoxazol administered intravenously is an option to treat cerebral toxoplasmosis if oral therapy is not feasible. CD4 T cell cut-off for starting prophylaxis with trimethoprim and sulfamethoxazole is now 200/µl. For prophylaxis and treatment of Pneumocystis pneumonia trimethoprim and sulfamethoxazole still are recommended. Liposomal amphotericin B + fluconazole is a new treatment option for cryptococcosis. Addition of steroids can be considered in the treatment of tuberculosis to avoid immune reconstitution inflammatory syndrome. A new syndrome associated with HHV8 has been described: Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS). Localization and dissemination of herpes zoster have to be considered for treatment determination.
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http://dx.doi.org/10.1055/a-0641-9456DOI Listing
December 2018
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