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Background Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete, long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. Here, we report the antiretroviral therapy as long acting suppression (ATLAS)-2M study week 152 results. Methods ATLAS-2M is a phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA every 8 weeks (Q8W) versus every 4 weeks (Q4W). Virologically suppressed (HIV-1 RNA Results A total of 1045 participants received CAB+RPV LA (Q8W, n = 522; Q4W, n = 523). CAB+RPV LA Q8W demonstrated noninferior efficacy versus Q4W dosing, with 2.7% (n = 14) and 1.0% (n = 5) of participants having HIV-1 RNA ≥50 copies/mL, respectively, with adjusted treatment difference being 1.7% (95% CI: 0.1–3.3%), meeting the 4% noninferiority threshold. At week 152, 87% of participants maintained HIV-1 RNA Conclusions These data demonstrate virologic suppression durability with CAB+RPV LA Q8W or Q4W for ∼3 years and confirm long-term efficacy, safety, and tolerability of CAB+RPV LA as a complete regimen to maintain HIV-1 virologic suppression.

Mantle shear-wave velocity models derived from seismic full waveform inversion methods reveal a very heterogeneous lithosphere-asthenosphere system beneath intracontinental Western and Central Europe north of the Alps. To better understand the physical state of the upper mantle in this region, we convert shear-wave velocity models to thermodynamically consistent temperature and density configurations using a Gibbs's free energy minimization approach. The inferred physical state of the lithosphere-asthenosphere system is then investigated for its consequences on past and present-day crustal deformation. For instance, a thermal lithosphere-asthenosphere boundary that varies in depth between > 200 km in the southern North Sea and

We present the second generation of the Collaborative Seismic Earth Model (CSEM), a multi-scale global tomographic Earth model that continuously evolves via successive regional and global-scale refinements. Harvesting the distributed human and computation power across the tomography community, the CSEM framework allows to systematically build on previously accumulated knowledge. This is achieved by providing the current version of the CSEM as a starting model for regional tomographic studies and incorporating these findings into the following version of the CSEM. The CSEM hosts 21 refinements from full seismic waveform inversion with diverse regional scales ranging from hundreds of km to entire continents. Noticeable changes since the first generation include detailed local updates for the Central Andes, Iran, South-east Asia, and the Western US, and continental scale refinements for Africa and Asia. A global long-period model improves the resolution int areas that have not been covered by other refinements. The current CSEM combines three-component waveform data from 1,637 events and over 700,000 unique source-receiver pairs across all regional updates.To complete the model, we perform a global full waveform inversion over multiple period bands to a minimum period of 50 s. With this approach we ensure waveform prediction across regional model boundaries and that the resolved Earth structure is part of a single coherent model. We demonstrate seismic waveform prediction of minimum periods of 50 s on the global scale and for 20 s to 30 s in selected areas. Active participation in the project is encouraged., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Purpose To describe the humoral immune response to COVID-19 vaccines in people living with HIV and identify factors associated with the magnitude of anti-SARS-CoV-2 antibody concentrations. Methods Retrospective analysis of electronic patient files in a big single HIV center in Munich, Germany. Non-parametric methods were used for descriptive and comparative statistics. Generalized linear models were used to analyze associations of general and HIV-specific variables with anti-SARS-CoV-2 antibody concentrations after standard vaccination. Result Overall, 665 people living with HIV were included into the analysis (median age: 53 [IQR: 43; 59]), 560 [84.2%] males). Median concentration of anti-SARS-CoV-2-antibodies was 1400 (IQR 664; 2130) BAU/mL. In 18 (2.7%) subjects, antibody concentrations below the threshold of 34 BAU/mL were found. Among PLWH with CD4 cell count

Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p Interpretation: A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.

in press Background Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. Methods This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. Conclusions In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

BACKGROUND: Many cases of monkeypox have been reported across Europe from early May 2022 onward. Initial publications suggest that nearly all of the affected persons to date have been men who have sex with men (MSM). METHODS: To characterize the German cases, an anonymous questionnaire was sent via the mailing lists of the German AIDS Society (Deutsche AIDS-Gesellschaft, DAIG) and the German Association of Outpatient Physicians for Infectious Diseases and HIV Medicine (Deutsche Arbeitsgemeinschaft ambulant tätiger Ärztinnen und Ärzte für Infektionskrankheiten und HIV-Medizin e.V., DAGNAE). RESULTS: 301 PCR-verified cases had been registered as of 23 June 2022. All of the affected persons were MSM, including 141 (46.7%) with HIV infection and 135 (44.7%) with pre-exposure prophylaxis (PrEP). The great majority of skin lesions were in the anal and genital areas. The most common general symptoms were fever, headache, limb pain, and, often, painfully swollen lymph nodes. Most infections to date have taken a relatively mild course: 5.0% of the patients were hospitalized, and none died. A high frequency of sexually transmitted infections (STI) was noted: only 41.0% of the patients had not been given a diagnosis of an STI in the six months before their monkeypox infection. CONCLUSION: Monkeypox seems to be establishing itself as a new type of STI among MSM. In view of the rising case numbers, there is a need for a rapid information and vaccination campaign in the population at risk. Heightened alertness among physicians is needed as well.

In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America. With the first two German cases, we are providing clinical and virological findings, including the detection of monkeypox virus DNA in blood and semen. It is important to raise awareness among health professionals of the rapid and correct identification and diagnosis of this disease, which is probably still under-reported in Europe. We describe the first two cases of monkeypox (MPX) infections in Germany to highlight the importance of recent developments for health professionals worldwide and to share further observations related to human-to-human transmission in these cases. MPX is an orthopoxvirus infection that, with the exception of a few imported cases in the past, was previously thought to be endemic only in West and Central African countries [1, 2]. Beginning in 2018, the United Kingdom (UK) Health Security Agency has reported several imported cases associated with travellers from these countries [3]. One case reported on May 7, 2022, had a travel history to Nigeria. However, the two other cases within a family reported on May 13, 2022, neither had a travel history nor an epidemiological link to the previous case. On May 17, 2022, four additional UK cases were reported involving individuals who described themselves as belonging to the group of men who have sex with men (MSM). Subsequent testing for monkeypox virus (MPXV) in symptomatic MSM patients reporting to sexual health and sexually transmitted disease (STD) clinics in the UK and elsewhere revealed an increasing number of confirmed MPX cases in Europe [1].

Introduction HIV infection has become a chronic, well-treatable disease and the focus of caretakers has shifted to diagnosis and treatment of comorbidities. Hypogonadism in elderly men with HIV might be of particular relevance, however, little is known about its epidemiology in contrast to non-infected peers and men with other chronic medical conditions, such as type 2 diabetes. This study aimed at comparing the prevalence of testosterone deficiency and functional hypogonadism in men ≥ 50 years in these three groups. Patients and Methods Multi-center, cross-sectional substudy of the German-wide 50/2010 study, including men aged 50 years or older with HIV-infection, type 2 diabetes, and controls. Results Altogether, 322 men were included (mean age: 62 years (SD±7.9)). The prevalence of testosterone deficiency in men living with HIV, type 2 diabetes, and controls was 34.5, 44.9, and 35.0%, respectively; the prevalence of functional hypogonadism was 7.7, 14.3 and 3.5%, respectively. Single-factor ANOVA demonstrated significant differences between the groups for total testosterone (p Discussion Despite a comparable prevalence of testosterone deficiency, functional hypogonadism was more frequent in men living with HIV when compared to non-infected controls. This was the result of a higher burden of symptoms that might, however, also be secondary to other conditions. Number of comorbidities was a more important factor than belonging to one of the groups.

Purpose This study aimed to determine the proportion of people living with HIV with anti-SARS-CoV-2 IgG antibodies in a sample from a large single HIV center in Munich, Germany, after the first phase of the coronavirus pandemic and to infer the prevalence of SARS-CoV-2 co-infection in people living with HIV. Methods Prospective sub-study of the ongoing ArcHIV cohort between May and July 2020. Anti-SARS-CoV-2 IgG antibodies were measured using the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Neuried, Germany); positive and borderline results were re-tested using the recomLine SARS-CoV-2 IgG immunoassay (Mikrogen, Neuried, Germany). Demographic and medical data were extracted from the electronic patient files. Results Overall, 500 people living with HIV were included in the study (83% male, median age 51 years). Three participants had been diagnosed with COVID-19 prior to study inclusion. Of those, nine were confirmed positive for SARS-CoV-2 IgG antibodies, resulting in an estimated seroprevalence (accounting for sensitivity and specificity of the test) of 1.5% (CI 95%: 0.69; 3.13) for the entire study sample, and 2.2% (CI 95%: 1.1; 3.9) for the subset of the Munich citizens. There were no marked differences for people living with HIV with and without SARS-CoV-2 co-infection. Conclusion The seroprevalence of SARS-CoV-2 co-infection in people living with HIV as found in our study does not seem to exceed previous reports from general populations of ‘hot-sport’ areas; comparative data from the Munich population can be expected to be published soon. Our data also highlight, once more, the need to do confirmatory testing on positive samples to minimize the impact of false-positive results.

Die meisten Menschen mit HIV-Infektion konnen derzeit gut behandelt werden, oftmals mit nur einer Tablette taglich, bestehend aus zwei oder drei antiviralen Wirkstoffen. Dank kontinuierlicher Forschung macht der Fortschritt nicht Halt. Zu den neuen Entwicklungen der antiretroviralen Therapie zahlen sowohl Substanzen mit neuen Wirkmechanismen als auch langwirksame Medikamente mit neuen Applikationsformen.

Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. 80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine ( 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding. Angiodysplasien (AD) sind häufig Ursache von gastrointestinalen Blutungen. Wir wissen wenig über Risikofaktoren, die Blutungen aus diesen Gefäßmissbildungen begünstigen können. Die gegenwärtige Studie hatte zum Ziel, Faktoren zu bestimmen, die nur bei Patienten mit symptomatischen, nicht aber bei Patienten mit asymptomatischen AD eine Rolle spielen. Fallkontrollstudie mit AD-Patienten entweder mit oder ohne Nachweis einer gastrointestinalen Blutung. Die beiden Gruppen wurden hinsichtlich klinischer, laborchemischer und endoskopischer Parameter verglichen. 80 Patienten mit blutenden (58, f 31, mitt. Alter 72) oder nicht blutenden AD (22, f 12, mitt. Alter 61) aus vier Krankenhäusern in München wurden eingeschlossen. Eine Blutung aus AD war signifikant mit der absoluten Zahl der AD (OR 1,4 (95 %-KI 1,1–1,7) P = 0,01) und der Verschlusszeit im PFA/Adrenalin-Test (OR 6,6 (95 %-KI 1,8–23,4) P = 0,004) assoziiert. Die absolute Zahl von AD korrelierte signifikant mit dem Alter (r = 0,369, P = 0,001). Die Mehrzahl der AD wurde im oberen Dünndarm ( 30 %) diagnostiziert. Obwohl Patienten mit Aortenstenose nicht signifikant häufiger aus AD bluteten, wiesen sie einen Verlust der hochmolekularen Multimere des Von-Willebrand-Faktors auf. Die Zahl der AD korreliert signifikant mit dem Alter der Patienten. Eine höhere Zahl von AD und eine Hemmung der primären Hämostase sind Hauptrisikofaktoren für eine mit AD assoziierte Blutung.

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Background: Small experimental studies suggest that PTH-secretion following hypocalcemia might be blunted in people living with HIV. Objective: The aim of the study was to estimate the frequency of inadequately low concentrations of parathyroid hormone in the presence of hypocalcemia in people living with HIV. Methods: This was a retrospective study that was conducted among PLWH enrolled in the ongoing ArcHIV study between 2016 and 2017. PLWH with routine measurements for both calcium and parathyroid hormone levels were included in this analysis. The proportion of patients with a combination of low levels of both calcium and parathyroid hormone was the primary endpoint of this analysis. Result:: 496 PLWH were included (mean age 47.1 (± 10.2) years, 393 (79.2 %) men). In 14 (2.8 %) PLWH, low calcium levels with low levels of PTH were observed in the assessment conducted in both years. Undergoing a tenofovir disoproxil-containing treatment in both years was the only explanatory variable significantly associated with inadequately low levels of PTH in the presence of hypocalcemia in both years (OR 4.3 [CI95: 1.4; 16.0]). Conclusion: The combination of low levels of both calcium and PTH was found more frequent in our study sample when compared to what is expected from the general population. Interestingly, undergoing a tenofovir disoproxil-containing therapy was associated with this combination throughout both the years.

Cardiovascular disease is an important contributor to morbidity and mortality in people living with HIV . The immature platelet fraction (IPF) is increased in HIV-negative patients with cardiovascular disease and evidence suggests that an enlarged IPF is associated with adverse cardiovascular events. In this multi-center observational study, we aimed to investigate how the IPF in people living with HIV is influenced by antiretroviral therapy and cardiovascular disease. Subjects without cardiovascular disease that received antiretroviral therapy showed a smaller IPF accompanied by lower D-dimer and C-reactive protein (CRP) levels compared to therapy-naïve subjects (mean IPF: 2.9% vs. 3.9%

Eine Vielzahl zellularer und nicht-zellularer (humoraler) Entzundungsparameter konnen heute von Laboratorien — teilweise auch vor Ort — und meist in kurzer Zeit bestimmt werden. Sie eignen sich daher dazu, klinische Verdachtsdiagnosen zu erharten oder auszuschliesen. Zusammen mit weiteren klinischen Befunden konnen Sie die Grundlage zur Veranlassung weiterfuhrender Diagnostik sein. Welcher Entzundungsparameter der „nutzlichste“ ist, hangt dabei masgeblich von der klinischen Fragestellung ab. Durch unterschiedliche Eigenschaften der Entzundungszeichen kann besonders die Kombination verschiedener Parameter sehr hilfreich sein. Mittlerweile konnen Entzundungsparameter auch die Indikationsstellung einer antibiotischen Therapie unterstutzen und fur deren Erfolgskontrolle herangezogen werden. Dies dient nicht nur der adaquaten Versorgung einzelner, betroffener Patienten sondern auch der Rationalisierung des Einsatzes von Antibiotika.

Hyperparathyroidism has been described in people living with HIV undergoing tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART), but differences in calcium levels have never been investigated in detail. We aimed to compare the prevalence of hypocalcemia between patients with and without TDF-containing ART. The patients and methods were a retrospective cohort study in HIV-infected adult patients receiving dolutegravir and either abacavir (ABC)/lamivudine (3TC) or TDF/emtricitabine in a single center in Munich, Germany. Of 172 patients, 126 (73.3%) were male and the median age was 48.5 years (interquartile range 42–54). Average calcium levels were 2.24 (2.21–2.29) mmol/l and 2.21 (2.16–2.26) mmol/l (P

Background: The prevalence of SARS-CoV-2 coinfection in people living with HIV has not been investigated systematically. Based on several considerations it is, however, unclear if data from general populations can serve as a reference. This study aimed to determine the proportion of people living with HIV with anti-SARS-CoV-2 IgG-antibodies in a sample from a large single HIV center in Munich, Germany, after the first phase of the coronavirus pandemic and to infer about the prevalence in people living with HIV. Methods: Prospective sub-study of the ongoing ArcHIV cohort between May and July 2020. Anti-SARSCoV-2 IgG-antibodies were measured using the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Neuried, Germany). Demographic and medical data were extracted from the electronic patient files. Findings: Overall, 500 people living with HIV were included in the study (83% male, median age: 51 years). Of those, 22 were found to be positive for SARS-CoV-2 IgG antibodies (0.044), resulting in an estimated seroprevalence (considering sensitivity ans specificity of the test) of 5.1 % (CI95%: 3.17; 7.02) for the entire study sample, and 5.2 % (CI95%: 2.62; 7.69) for the subset of Munich citizens. Only two out of 22 PLWH (9.1%) with positive SARS-CoV-2 serology had previously been diagnosed with SARS-CoV-2 coinfection. The proportion of Caucasian people living with HIV was significantly smaller in the group with positive when compared to the group of negative test results (68.2% vs. 88.1%, p=0.021). Interpretation: Anti-SARS-CoV-2 antibodies are frequently found in people living with HIV. Many people are olig- or asymptomatic but probably still able to pass the infection to others. Racial disparities seem to play a role in the risk of exposure to SARS-CoV-2 even in high-income areas. Funding: Mikrogen GmbH (Neuried, Germany) provided the test kits used in this study. The funding source was not involved in any aspects of the study. Declaration of Interests: All authors declare support for the study from Mikrogen GmbH (Neuried, Germany) by providing test kits used in this study. SN reports honoraria and/or grants for research or travel from Gilead Sciences, GSK, MSD Sharp & Dohme, Hexal, Hormosan Pharma, HRA Pharma, Ipsen Pharma, Janssen-Cilag, Shire Pharmaceuticals, and ViiV Healthcare. FS reports honoraria and/or grants for research or travel from Abbvie, Gilead Sciences, Hexal, Janssen-Cilag, and MSD Sharp & Dohme. SH reports honoraria and/or grants for research or travel from Abbvie, Gilead Sciences, and Janssen-Cilag. KR reports grants for travel from Abbvie and Gilead Sciences. CJ reports honoraria and/or grants for research or travel from Abbvie, Gilead Sciences, GSK, Janssen-Cilag, and ViiV Healthcare. HJ reports honoraria and/or grants for research or travel from Abbvie, Gilead Sciences, GSK, Janssen-Cilag, and ViiV Healthcare. EW reports honoraria and/or grants for research or travel from Abbvie, Gilead Sciences, GSK, Janssen-Cilag, and ViiV Healthcare. WM, FT, AK, CW, AB, and EG have nothing else to disclose. Ethics Approval Statement: This study was performed as a prospective, cross-sectional sub-study of the Munich ArcHIV cohort, an ongoing cohort in PLWH in Munich, Germany, with approval of the local ethic’s committee dating May 28th, 2020.

Secondary hyperparathyroidism (sHPT) might be a contributor to increased risk of osteoporosis in adult HIV patients but there is little data available on this issue in this particular population. The aim of the study was to investigate the prevalence of sHPT in an HIV-infected population with normal kidney function and to evaluate its risk factors in HIV patients. This cross-sectional study was carried out in a single HIV center in Germany using routine data from patients with normal kidney function attending the clinic between January 1st and December 31st, 2016. In total, 1263 patients were included [998 (79.0%) male, median age 48 (IQR 38–54) years]. In 214 patients (16.9%) elevated PTH levels with low or normal calcium levels were found. Multivariate logistic regression modeling showed significant associations with elevated PTH for African ethnicity [OR: 2.12 (95% CI: 1.42–3.16); p

Johanna Boretzki,1,2 Eva Wolf,3 Carmen Wiese,4 Sebastian Noe,4 Annamaria Balogh,3 Anja Meurer,5 Ivanka Krznaric,6 Alexander Zink,7 Christian Lersch,1 Christoph D Spinner1,2 1Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, 2German Center for Infection Research, Partner Site Munich, 3MUC Research, Munich, 4MVZ Karlsplatz, HIV Clinical Care Center, Munich, 5Center for Infectiology and Internal Medicine, Munich, 6Center for Infectiology Prenzlauer Berg, Berlin, 7Department of Dermatology and Allergology, University Hospital Klinikum rechts der Isar, Munich, Germany Background: Reasons for and frequency of nonadherence to antiretroviral therapy (ART) may have changed due to pharmacological improvements. In addition, the importance of known non-pharmacologic reasons for nonadherence is unclear.Methods: We performed a cross-sectional, noninterventional, multicenter study to identify current reasons for nonadherence. Patients were categorized by physicians into the following adherence groups: good, unstable, or poor adherence. Co-variables of interest included age, sex, time since HIV diagnosis, ART duration, current ART regimen, HIV transmission route, comorbidity, HIV-1 RNA viral load (VL), and CD4 cell count. Patients self-reported the number of missed doses and provided their specific reasons for nonadherent behavior. Statistical analyses were performed using Fisher’s extended exact test, Kruskal–Wallis test, and logistic regression models.Results: Our study assessed 215 participants with good (n=162), unstable (n=36), and poor adherence (n=17). Compared to patients with good adherence, patients with unstable and poor adherence reported more often to have missed at least one dose during the last week (good 11% vs unstable 47% vs poor 63%, p

Sinus rhythm (SR) and controlled mechanical ventilation (CV) are mandatory for the applicability of respiratory changes of the arterial curve such as stroke volume variation (SVV) to predict fluid-responsiveness. Furthermore, several secondary limitations including tidal volumes

Background The potential toxicity of long-term anti-retroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infected patients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse. Methods Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level Results We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained Conclusions De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG mono-therapy failure. In the meanwhile, caution is warranted.

Insulin resistance (IR) was one of the first reported complications in HIV-positive patients who were receiving antiretroviral therapy (ART). However, the metabolic effects of newer fixed-dose ART combinations are unclear.This Phase I prospective randomized open-label study evaluated the effects on IR in 30 healthy volunteers who were receiving newer fixed-dose combinations of tenofovir disoproxil fumarate, emtricitabine, elvitegravir and cobicistat (E/C/F/TDF, 10 patients) or the established ART regimens, such as tenofovir disoproxil fumarate/emtricitabine with lopinavir/ritonavir (F/TDF+LPV/r, 9 patients) or darunavir/ritonavir (F/TDF+DRV/r, 9 patients). IR was measured before and after the 14-day treatments using the hyperinsulinemic-euglycemic clamp technique, and changes in IR were evaluated using the mean glucose disposal rate that was normalized to body weight (MThe groups exhibited similar pretreatment IR, although MShort-term treatment using fixed-dose combinations of E/C/F/TDF or F/TDF+DRV/r did not affect IR, although IR significantly increased after treatment using F/TDF+LPV/r.

Die Entwicklung von HIV-Medikamenten geht in die nachste Phase. Lang wirksame Depotpraparate fuhrten in klinischen Studien bereits zu ersten Erfolgen. Patienten, die nur alle vier bis acht Wochen ihre Medikamente injizieren mussten, zeigten sich zufrieden.

We present the case of a 58-year-old HIV-infected patient with adrenal insufficiency after local injection of triamcinolone, most likely due to drug–drug interaction with his ritonavir-boosted antiretroviral therapy (ART). This is the first case of adrenal insufficiency occurring without prior symptoms of Cushing’s syndrome in a patient on a booster-containing ART. We want to draw attention to this seemingly rare, but potentially life-threatening medical condition that can occur even in short-term use of glucocorticoids in low doses in patients on booster-containing ART and summarize some considerations for management.

Background. There is still considerable uncertainty in handling vitamin D deficiency in people living with HIV (PLWH), due to a lack of comparative data and the wide range of recommended daily intake. Nondaily supplementation might be preferred in many PLWH, but recommendation on dosing has not been established. We aimed to compare the efficacy of weekly versus monthly supplementation with cholecalciferol 20,000 IU in a group of PLWH with vitamin D deficiency in Western Europe. Study Design. Longitudinal, retrospective nested cohort study of PLWH from two large clinical care centers in Munich, Germany. Results. Of 307 patients with vitamin D deficiency, 124 patients received vitamin D supplementation (weekly supplementation in 84 (67.7%)). 46.4% and 22.5% of patients achieved 25(OH)D levels ≥30 ng/mL after 12 months of weekly and monthly supplementation with cholecalciferol 20,000 IU, respectively (p=0.011). Dosing interval as well as 25(OH)D baseline levels >15 ng/mL were associated with the normalization of 25(OH)D. Conclusion. A higher rate of 25(OH)D level normalization can be achieved via weekly supplementation. For several PLWH, even a weekly dose of cholecalciferol 20,000 IU might not be adequate to maintain 25(OH)D levels >30 ng/mL without an initial “loading” dose. The response to supplementation is poorly predictable at an individual level.

Background. Higher levels of parathyroid hormone have been associated with the use of tenofovir disoproxil fumarate (TDF) in people with and without HIV infection. Yet, alterations in calcium levels have never been elucidated in detail. Objective. To compare the association of parathyroid hormone with serum calcium levels and other markers of calcium and bone metabolism in people living with HIV on TDF- and non-TDF-containing antiretroviral therapy. Patients and Methods. A retrospective single center cohort study in Munich, Germany. Median and interquartile ranges and absolute and relative frequencies were used to describe continuous and categorical variables, respectively. The Mann–Whitney U test and chi2-test were used for comparisons. Multivariate median regression was performed in a stepwise backward approach. Results. 1,002 patients were included (786 (78.4%) male; median age 48 (40–55) years). 564 patients (56.3%) had a TDF-containing ART regimen. PTH concentrations were 46.9 (33.0–64.7) pg/mL and 35.2 (26.4–55.4) pg/mL (P=0.001), 43.3 (30.8–59.8) pg/mL and 31.8 (22.3–49.6) pg/mL (P<0.001), 46.1 (29.5–65.4) pg/mL and 33.4 (22.6–50.1) pg/mL (P<0.001), and 37.8 (25.3–57.9) pg/mL and 33.8 (20.1–45.3) pg/mL (P=0.012) within the first, second, third, and fourth quartile of corrected calcium levels for patients with and without TDF-containing ART, respectively. In multivariate median regression, PTH concentration was significantly associated with Cacorr. (−32.2 (−49.8 to −14.8); P<0.001), female sex (5.2 (1.2–9.2); P=0.010), 25(OH)D (−0.4 (−0.5 to −0.3); P<0.001), and TDF-use (9.2 (6.0–12.5); P<0.001). Discussion. Higher levels of PTH seem to be needed to maintain normal calcium levels in PLWH on TDF-containing ART compared to non-TDF-containing ART. Optimal concentrations for 25-hydroxy vitamin D and calcium might therefore be different in people using TDF than expected from general populations but also people living with HIV with non-TDF-containing antiretroviral therapy. This might require different supplementation strategies but warrants further investigation.

Purpose: To evaluate efficacy and safety of 20 000 IU cholecalciferol weekly in HIV-infected patients. Methods: Longitudinal data for 243 HIV-infected patients with paired 25-OH-vitamin D3 values for the same month in 2 consecutive years were stratified by the initiation of supplementation in this retrospective study. Results: After 1 year of administration of cholecalciferol 20 000 IU weekly, about 78% of patients with initial vitamin D level 20 µg/L and 42% achieved levels >30 µg/L. Supplemented patients with baseline vitamin D levels Conclusion: The dose of 20 000 IU of cholecalciferol once weekly was found to be safe and effective. Normalization of vitamin D levels within 1 year was observed in 42% to 75% of the patients.

An increased release of serotonin secreted by ileal NETs is thought to be the major factor causing the carcinoid syndrome. However, in acutely arising carcinoid crisis also other vasoactive factors may lead to hazardous fluctuations in blood pressure and bronchial constriction. In rare cases, systemic vasoconstriction can be observed, probably caused by catecholamines or similar acting substances. Here, we report a fatal case of fulminant systemic vasoconstriction possibly caused by catecholamines in a patient with metastasized ileal NET. The vasospasm was detected by CT-angiography, and hemodynamic monitoring revealed a high systemic vascular resistance. Epinephrine, norepinephrine, and chromogranin A levels in plasma were elevated as was the urinary 5-hydroxyindoleacetic acid (5-HIAA). The cause of death was heart failure due to severe circulatory insufficiency. The progression of the tumor disease was confirmed by autopsy.

Neuroendokrine Neoplasien werden immer noch in ihrer Haufigkeit unterschatzt. Fruher teilweise als eher gutartige Tumoren angesehen, betrachtet man sie nun alle als potenziell maligne. Die Kenntnisse „typischer“ Symptome ist wichtig, denn werden diese erkannt, so konnen betroffene Patienten einer adaquaten Diagnostik zugefuhrt werden. Leider lassen selbst die als charakteristisch angesehenen Symptome viele, weitaus haufigere Differenzialdiagnosen zu und sind selten – und dann meist erst in spateren Krankheitsstadien – von vornherein wegweisend. Heute stehen in der Diagnostik hervorragende biochemische, endoskopische, radiologische und nuklearmedizinische Optionen zur Verfugung. Ihre sinnvolle Kombination erlaubt eine fruhe(re) Diagnosestellung, Risikostratifizierung, Festlegung des individuellen Therapiekonzepts und optimale Nachsorge.