BACKGROUND:More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern. The third-generation smallpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox. METHODS:We did a prospective, multicentre, observational study, enrolling men who have sex with men and transgender people aged 18 years or older with changing sexual partners in Germany (Safety and Effectiveness of MVA-BN Vaccination Against MPXV Infection [SEMVAc]) between July 7, 2022, and Dec 31, 2023, evaluating safety and reactogenicity of one and two doses of subcutaneous MVA-BN. Vaccine effectiveness was estimated using risk ratios from the Kaplan-Meier estimator in an emulated retrospective target trial (Emulated Target Trial for Effectiveness of MVA-BN Vaccination Against mpox Infection in At-risk Individuals [TEMVAc]) from 3027 vaccinated individuals matched (1:1) to 3027 unvaccinated controls. SEMVAc and TEMVAc were registered in the HMA-EMA Catalogue, EUPAS50093, and the German Clinical Trials Register, DRKS00029638, and are complete. FINDINGS:6459 individuals were prospectively enrolled in SEMVAc. Adverse reactions were infrequent (first dose: 0·35% [95% CI 0·20-0·60] and second dose: 0·14% [0·06-0·33]). Local reactions were more frequent after the first dose (70·2% [95% CI 68·5-71·8]) compared with the second dose (56·8% [54·6-59]), as were systemic reactions (first dose, 22·3% [95% CI 20·9-23·9]; second dose, 17·6% [15·9-19·4]). In TEMVAc, 16 mpox cases were reported in vaccinated individuals versus 32 cases in matched unvaccinated individuals (median follow-up 55 days [IQR 23-89]). Effectiveness by 14 days or later after one dose was 57·8% (95% CI 11·8 to 83·0) overall, 84·1% (42·0 to 100) in people without HIV, but 34·9% (-72·8 to 79·0) in people living with HIV. Breakthrough infections were associated with reduced symptoms, compared with infections in unvaccinated individuals. INTERPRETATION:MVA-BN vaccination was safe and well tolerated. One dose of MVA-BN offered protection against mpox but effectiveness was reduced in people living with HIV. Although randomised controlled trials remain the preferred approach for assessing vaccine efficacy, combining prospective and retrospective study designs can be valuable during dynamic public health emergencies. FUNDING:European Medicines Agency. TRANSLATION:For the German translation of the abstract see Supplementary Materials section.

PURPOSE:Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS:We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS:In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION:The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.

OBJECTIVES:To identify sexual/sex-associated risk factors for hepatitis C transmission among men who have sex with men (MSM) and visualise behavioural trajectories from 2019 to 2021. METHODS:We linked a behavioural survey to a hepatitis C cohort study (NoCo), established in 2019 across six German HIV/hepatitis C virus (HCV) treatment centres, and performed a case-control analysis. Cases were MSM with recent HCV infection, and controls were matched for HIV status (model 1) or proportions of sexual partners with HIV (model 2). We conducted conditional univariable and multivariable regression analyses. RESULTS:In all, 197 cases and 314 controls completed the baseline questionnaire and could be matched with clinical data. For regression models, we restricted cases to those with HCV diagnosed since 2018 (N = 100). Factors independently associated with case status included sex-associated rectal bleeding, shared fisting lubricant, anal douching, chemsex, intravenous and intracavernosal injections, with population-attributable fractions of 88% (model 1) and 85% (model 2). These factors remained stable over time among cases, while sexual partner numbers and group sex decreased during COVID-19 measures. CONCLUSIONS:Sexual/sex-associated practices leading to blood exposure are key factors in HCV transmission in MSM. Public health interventions should emphasize the importance of blood safety in sexual encounters. Micro-elimination efforts were temporarily aided by reduced opportunities for sexual encounters during the COVID-19 pandemic.

Abstract Introduction During the mpox outbreak in 2022, the highest number of cases in Germany were registered in Berlin, almost all of them in men who have sex with men (MSM). However, the frequency of clinically undiagnosed infections is unknown. Methods A cross-sectional study was conducted among MSM in Berlin, Germany. Participants were recruited from private practices and community-based checkpoints specialised in HIV and STI care for MSM. They were asked to complete an online questionnaire on socio-demographic data, mpox diagnosis, vaccination history and sexual behaviour, and to provide a blood sample for serological analysis. The samples were tested for antibodies against a range of antigens to distinguish between antibodies induced by mpox infection and MVA vaccination, with pre-immune sera from childhood smallpox vaccination as a confounding factor. Associations of behavioural variables with reported and suspected mpox diagnosis as the outcome were tested using univariable and multivariable logistic regression models. Results Between the 11th April and 1st July 2023, 1,119 participants were recruited in eight private practices and two community-based checkpoints in Berlin. All participants provided a blood sample for serological testing. Information for the online questionnaire was provided by 728 participants; core data on age and mpox history for participants who did not provide questionnaire data were provided by the practices for an additional 218 participants. A previous diagnosis of mpox was reported for/by 70 participants (7.4%). Using a conservative and strict case definition, we serologically identified an additional 91 individuals with suspected undiagnosed mpox infection. Individuals with reported or suspected mpox infections reported more condomless anal sex partners in the past 3 months (OR = 5.93; 95% CI 2.10-18.35 for 5–10 partners; OR = 9.53; 95% CI 2.72–37.54 for > 10 partners) and were more likely to report sexual contact with partners diagnosed with mpox (OR = 2.87; 95% CI 1.39–5.84). Conclusion A substantial proportion of mpox infections were clinically undiagnosed. The number of condomless anal sex partners was strongly associated with both confirmed and suspected undiagnosed mpox infection. Therefore, mpox control measures based on clinical diagnosis of mpox are likely to have limited effectiveness in preventing mpox transmission in outbreak situations because many infections remain unrecognised and undiagnosed.

INTRODUCTION:Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. METHODS:The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented. RESULTS:A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis. CONCLUSIONS:High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m(2) (IQR, 23.6-28.7 kg/m(2)); metabolic syndrome (67%); and CD4 cell count, 630/mm(3) (IQR, 510-832/mm(3)). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF >= 5%). Among them, 11.3% had a liver stiffness >= 9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23; 95% CI, 1.07-1.42; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operating characteristic curve = 0.86; 95% CI, 0.82-0.90) for the diagnosis of moderate to severe steatosis. CONCLUSIONS: In a large cohort of HIV-moninfected patients at risk of NAFLD, steatosis is present in two-thirds of cases, and around 10% have AF. The CAP technique is accurate for screening steatosis in this population.

Abstract Introduction Directly-acting antivirals (DAA) are the cornerstone to reach HCV elimination. In men who have sex with men (MSM) with HIV coinfection, recently acquired HCV infection (RAHCV) is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. Methods The cohort included MSM with RAHCV from 2014 to 2021. The patients’ demographic, clinical, behavioral, and laboratory data were documented, as well as treatment and reinfection outcomes. Results 237 men with RAHCV were included, 216 (91%) were PLWH. Median age was 46 years (IQR: 39–52), median CD4 count was 660/mm3 (IQR: 527–835). The annual incidence of RAHCV remained between 0.28% and 0.43%, but dropped to 0.02% in 2021 during the onset of the COVID-pandemic almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95%-CI: 12.6-18.8), reinfection was associated with use of crystal methamphetamine (p=0.032) and ketamine (p=0.042). 31.3% had multiple reinfections, four reinfections occurred in PrEP users. Conclusions High treatment and cure rates did not lead to HCV elimination. A change in sexual behavior, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As RAHCV is prevalent in HIV-positive and -negative MSM, surveillance is necessary to consolidate elimination goals.

Background The transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory. Method From 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports. Results Among all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse-transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (p Trend =0.024) during 2017–2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (p Trend =0.049) while the frequency of minority subtypes (each < 1%) increased (p Trend =0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%). Conclusion The percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.

Background Instruments controlling statutory healthcare medical supply have long been a topic of debate in health policy reform discussions. Over the years, a variety of tools have been developed, most of which are aimed at controlling drug expenditure. The instruments controlling regional prescriptions primarily focus on controlling behavioural patterns of the prescribing physicians. Important to note is the increased use of indication-directed quotas, primarily of drug leads and/or generics/biosimilars. These are now also available in the area of the human immunodeficiency virus (HIV), such as the generic quotas for HIV medications introduced in Bavaria and Berlin in 2020. Objective The aim of this article is to analyse the benefits and limitations of generic quota solutions in HIV care using statutory health insurance drug prescription data and to outline recommendations for action. Results It was observed that the quota potential for generics in the area of patent-free drugs in HIV care has already been largely exhausted. This can be explained by HIV prescribers supporting product exchange on the prescription. Discussion The best-case scenario in terms of regulation has almost been reached. This is due to a suitable set of instruments, including the framework agreement for medical supply as well as prescribing according to guidelines - in conjunction with the Pharmaceuticals Market Reorganisation Act (AMNOG) and reference prices for drugs. Conforming with guidelines and (existing) single-tablet regimens play an integral role in maintaining good quality of care.

Chronic liver disease due to hepatitis C virus (HCV) infection is a major public health burden with an estimated 71 million people worldwide suffering from replicative HCV infection.1 Even if diagnosed in an early stage of disease, missing linkage to care or reluctance to treat might defer treatment until progression to an advanced stage of liver disease. To reduce liver-related morbidity and mortality by 65% by 2030 as targeted by the World Health Organization (WHO) innovative prevention measures, a timely treatment uptake and identification and well-managed care of those with advanced liver disease will be needed.2 In this context, a consensus definition of late presentation for viral hepatitis defining it as significant fibrosis (≥F3; advanced liver disease) or late-stage liver disease (hepatic decompensation or hepatocellular carcinoma (HCC)) in chronic viral hepatitis had been established to improve patient care and disease management across Europe.3 Using a common definition will allow cross-country or regional comparisons and an investigation of temporal trends after targeted interventions. With direct-acting antivirals (DAAs), a highly effective and well-tolerated HCV treatment can be offered almost to every patient. Achieving sustained virological response (SVR) after end of treatment equals HCV cure in most cases and has a beneficial impact on disease progression and liver-related complications. To reduce the burden of chronic viral hepatitis, access to DAAs is unrestricted in Germany. Late presentation (LP) might be different for patients coinfected with HIV and HCV compared to those monoinfected with HCV, as HIV accelerates liver disease progression and different patient populations might be affected, concerning mode of transmission, risk behaviour and genotype (GT). We aimed to investigate the extent of LP since unrestricted access to DAA therapy in Germany for HCV monoinfected and HIV/HCV coinfected patients in the period 2014–2018. The German Hepatitis C-Registry (DHC-R) is a national multicentre real-world cohort currently including about 17,700 patients recruited by more than 250 centres. It is registered at the German Clinical Trails Register (ID DRKS00009717). The study protocol was approved by the Institutional Review Board (Ethics Committee of Aerztekammer Westfalen-Lippe) and conducted in accordance with the Declaration of Helsinki. Treatment-naïve patients infected with HCV and aged ≥18 years, who have been screened and referred for treatment at one of the study-sites between 1 of February 2014 and 31 of December 2018 inclusive were included in our analysis. An informed consent form was mandatory for every patient to be registered. HCV monoinfected and HIV/HCV coinfected participants were analysed separately. In 2016, patients could be enrolled from August to December only, and therefore, data collected in 2016 was not included in our statistical analysis. Advanced liver disease (ALD) was defined according to the consensus definitions of late presentation for care.3 Advanced liver disease was defined as chronic hepatitis C and no previous antiviral treatment in case of an aspartate-aminotransferase-to-platelet-ratio-index (APRI) score ≥1.5, a transient elastography (FibroScan, Echosens, Paris, France) ≥9.5 kPa or a METAVIR stage ≥F3 determined by liver biopsy. Liver cirrhosis was diagnosed using a cirrhosis sum score. The cirrhosis sum score is defined as either one biopsy confirming cirrhosis (METAVIR F4) or one of the following findings: sonographically confirmed cirrhosis, clinical confirmation (e.g., ascites, oesophageal varices or bleeding, jaundice), an APRI-score ≥2 or a FibroScan ≥12.5 kPa. Statistical analysis was performed by e.factum GmbH (Butzbach, Germany) based on a database extract as of 20 January 2019. Summary statistics (mean, median, standard deviation, 25th percentile, 75th percentile, minimum, maximum, number of values) or frequencies and proportions were assessed dependent on the scale level of the data. Proportions of patients presenting with ALD by year were compared using chi-square tests, Mann–Whitney U test and Fisher's exact test. Differences were considered significant at p ≤ .05. All analyses were calculated using SPSS Windows Release 22.0.0.2 (IBM©, USA). Eight thousand three treatment naive patients were referred for DAA treatment in the observational period. 28% (2197/8003) of these patients already suffered from ALD. 62% (4995/8003) were male and the average age was 49.8 ± 13.2 years. HIV coinfection was present in 6.9% (551/8003) of patients. Hepatitis B virus (HBV) coinfection status was documented in 4323 (54%) patients and HBV coinfection was present in 116/4323 (2.7%) of patients. The most frequent GT in the overall study population was GT 1 (68%; 5410/8003) followed by GT 3 (23%; 1846/8003), GT4 (5%; 370/8003) and GT2 (4%; 367/8003). 6872 (86%) patients provided information on alcohol consumption and 1264/6872 (18%) of patients reported alcohol consumption of any amount. Mean BMI at baseline was 25.7 ± 4.8 kg/m2 (n = 7463). 85% (320/376) of HIV/HCV coinfected patients were virally suppressed (<40 cp/ml), and 448/551 (81%) were administered antiretroviral treatment (ART). A detailed description of baseline characteristics by liver disease and HIV/HCV coinfection status can be found in the supplemental digital content Tables S1–S7. LP for viral hepatitis was as high as 37% (439/1184) for treatment naive patients in 2014 and decreased significantly to 29% (873/3055; p < .001), 21% (368/1728; p < .001) and 26% (430/1655; p < .001) in 2015, 2017 and 2018, respectively (Figure 1). Lowest proportions of LP were observed in 2017 with no further decrease in 2018. In 2018, LP was significantly lower in patients being HIV/HCV coinfected compared to HCV monoinfected patients (p = .047). Overall, 28% (2197/8003) of patients presented with ALD, with the highest proportion (37%; 439/1184) in 2014. This finding is in line with results from Denmark and France and confirms our results from the GECCO cohort.4-6 Quite recently, reports from Spain for 2018 and 2019 demonstrated a stable prevalence of LP in the last years.7 Despite the broad availability of DAA treatment, the rate of patients already affected by ALD at time of treatment initiation remained at around 25%, with a significantly lower proportion only in HIV/HCV coinfected patients in 2018. We observed a significant decrease in the proportion of patients presenting late for viral hepatitis comparing 2014 to the following years 2015, 2017 and 2018. The largest drop was observed in the year from 2014 to 2015, which was likely due to the foreseeable approval of first-generation DAAs in 2012/2013 and an associated delay of treatment into the year 2014. Treatment uptake was about 3 times higher in 2015 compared to 2014 (1100 patients vs. 3055 patients), which reflects most likely the effect of the implementation of DAAs for HCV treatment and unrestricted access in Germany. But several reports observed that treatment uptake did not reduce the incidence of HCV infections in all high-risk groups.6, 8 Conceivably, (re-) infections, specifically in HIV-MSM using PrEP might counterbalance the effect of treatment uptake, highlighting the need for intensified prevention measures and behavioural changes.9 Data from several European countries reporting LP in >25% of HCV infected patients despite unrestricted access to DAA treatment is alarming, particularly under consideration that the proportion of LP in low- and middle-income countries might be even higher. Moreover, a possibly more difficult access to HCV treatment and expert service appointments from 2020 onwards due to the corona virus pandemic worldwide might cause a further increase in LP in the next years. Clearly, much greater efforts need to be made in terms of screening and early referral for treatment to achieve the WHO 2030 elimination targets. In our cohort, HIV/HCV coinfected patients presented less often with ALD in 2018 compared to those HCV monoinfected, highlighting the importance of a close linkage to care. The considerably high proportions of patients with ALD should bring the importance of a continued follow-up of these patients in expert centres into focus. In a retrospective analysis from Germany, de novo HCCs occurred in 3.1% of treated patients and all affected patients had underlying cirrhosis at treatment initiation or developed cirrhosis after treatment failure.10 Addressing the burden of severe liver disease is not only a matter of treatment and prevention but also an important task to prevent liver-related complications (decompensations, HCCs) effectively. Our study has some limitations. As there was an enrolment pause between October 2015 and July 2016, we could not evaluate LP in 2016, which would have been quite interesting, as we observed an increase in the proportion of LP in 2016 in the GECCO cohort.6 Furthermore, about 10% of patients might have contributed to the GECCO cohort as well, as there has been an overlap in the founding years of the GECCO registry. To conclude, 28% of treatment naïve patients with chronic HCV presented late for care in the years 2014–2018 in Germany. Although we observed a significant decrease of this proportion for HCV monoinfected and HIV/HCV coinfected patients, 27% of HCV monoinfected and 17% of HIV/HCV coinfected patients still presented with ALD in 2018 despite an increase in treatment uptake and unlimited access to DAAs. Our findings should contribute to improvement of diagnostic strategies and prevention measures to reduce the burden of LP and highlight the importance of a close long-term follow-up to prevent liver-related complications. Data were derived from the German Hepatitis C-Registry (Deutsches Hepatitis C-Register, DHCR) a project of the German Liver Foundation (Deutsche Leberstiftung), managed by Leberstiftungs-GmbH Deutschland in cooperation with the Association of German gastroenterologists in private practice (bng). The authors thank all study investigators, study nurses, and participating patients. Special thanks to Heike Pfeiffer-Vornkahl from e.factum GmbH for data analysis and statistics. Financial support was received from German Center for Infection Research (DZIF) and the companies AbbVie Deutschland GmbH & Co. KG, Gilead Sciences GmbH, MSD Sharp & Dohme GmbH as well as Bristol-Myers Squibb GmbH & Co. KGaA and Janssen-Cilag GmbH (each until 2020-07-14) and Roche Pharma AG (until 2017-07-14). Jenny Bischoff has nothing to disclose. Stefan Mauss reports personal fees (consulting or/and speaker fee) from AbbVie, Gilead, Janssen, MSD, MyrPharma, ViiV. Thomas Lutz reports Grants/research support from AbbVie, Gilead Siences, GSK, MSD, Deutsche Leberstiftung e.V., Heidelberger Immunotherapeutix, DAGNÄ e.V. Christiane Cordes has nothing to disclose. Gerd Klausen has nothing to disclose. Stefan Scholten: Advisory Committees or Review Panels: Abbvie, BMS, Gilead, GSK, Janssen-Cilag, MSD, ViiV Healthcare, TAD; Grants/Research Support: Abbvie, BMS, Gilead, Janssen-Cilag, MSD, ViiV Healthcare, Hexal; Speaking and Teaching: Abbvie, BMS, Gilead, Janssen-Cilag, MSD, ViiV Healthcare. Heribert Hillenbrand has nothing to disclose. Markus Cornberg reports personal fees (consulting or/and speaker fee) from Abbvie, Falk Foundation, Gilead, Janssen-Cilag, GSK, MSD, Spring Bank, SOBI, outside the submitted work. Axel Baumgarten has nothing to disclose. Jürgen K. Rockstroh: has received honoraria for consulting or speaking at educational events from Gilead, Janssen, Merck, ViiV and Theratechnologies. The DHC-R is registered at the German Clinical Trails Register (ID DRKS00009717). The study protocol was approved by the Institutional Review Board (Ethics Committee of Aerztekammer Westfalen-Lippe). Stefan Fenske, Katja Deterding, Carsten Zamani, Heribert Knechten, Ulrich Bohr, Christoph Schuler, Ute Merle, Christoph Stephan, Dietmar Schranz, Peter Buggisch, Hartwig Klinker, Ansgar Rieke, Hubert Schulbin, Ramona Pauli, Arend Moll, Pavel Khaykin, Albrecht Stoehr, Ulrich Rausch, Nils Postel, Markus Müller, Andreas Schober, Uwe Naumann, Heiner Busch, Hans Jäger, Rainer Günther, Tobias Glaunsinger, Dorothea Schleehauf, Thomas Heuchel, Stefan Christensen, Christoph Sick, Thomas Berg, Heinz Hartmann, Dietrich Hüppe, Michael PManns, Claus Niederau, Ulla Protzer, Christoph Sarrazin, Peter Schirmacher, Karl-Georg Simon, Heiner Wedemeyer, Stefan Zeuzem The data supporting the findings of this study are available from the corresponding author JKR upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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<0.001), SHBG (p<0.001), as well as for free testosterone concentrations (p=0.006). Comorbidities were, however, most important single factor in multi-factor analysis.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.

Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C. Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines.

BACKGROUND:Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.METHODS:In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm.RESULTS:Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.CONCLUSIONS:Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).

Background: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. Setting: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. Methods: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. Results: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. Conclusion: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

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.