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The ongoing monkeypox virus outbreak includes at least 7553 confirmed cases in previously non-endemic countries worldwide as of July 2022. Clinical presentation has been reported as highly variable, sometimes lacking classically described systemic symptoms, and only small numbers of cutaneous lesions in most patients. The aim of this study was to compare clinical data with longitudinal qPCR results from lesion swabs, oropharyngeal swabs and blood in a well characterized patient cohort.16 male patients (5 hospitalized, 11 outpatients) were included in the study cohort and serial testing for monkeypox virus-DNA carried out in various materials throughout the course of disease. Laboratory analysis included quantitative PCR, next-generation sequencing, immunofluorescence tests and virus isolation in cell culture.All patients were male, between age 20 and 60, and self-identified as men having sex with men. Two had a known HIV infection, coinciding with an increased number of lesions and viral DNA detectable in blood. In initial- and serial testing, lesion swabs yielded viral DNA-loads at, or above 10The data presented underscore the reliability of lesion swabs for monkeypox virus-detection, even in later stages of the disease. Oropharyngeal swabs and blood samples alone carry the risk of false negative results, but may hold value in pre-/asymptomatic cases or viral load monitoring, respectively.

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of observation was 451 days (IQR 357-488), totaling 5132 py.Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the covid-19 pandemic period.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Objectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.Anonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357-488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period.We found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Many patients infected with HIV are diagnosed at an advanced stage of illness. These late presenters are individuals with a CD4 cell count of less than 350 cells/µL and/or an AIDS defining disease at initial HIV diagnosis. Purpose of FindHIV is to develop and distribute a questionnaire/scoring system aimed at a reduction in late presentation. FindHIV uses a mixed methods approach. In a first step, primary data of patients were collected. Inclusion criteria were: age ≥ 18 years, cognitive ability and language skills to participate in the study, initial HIV diagnosis within the past 6 months, and patient informed consent. Descriptive methods and regression models are used to identify: (1) patient characteristics associated with late presentation and (2) contacts to the healthcare system with indicator diseases that did not lead to HIV testing. Secondly, a questionnaire/scoring system is created by an expert panel. Afterwards the questionnaire/scoring system is to be disseminated. The greatest challenge was in reaching an adequate sample size. Another risk may be a recall bias. Nevertheless, FindHIV is devised as an in-depth study of the phenomenon of late presentation with potential to significantly improve HIV detection.

Objectives The purpose of the prospective clinical and pharmacoeconomic outcomes study of different first-line antiretroviral treatment strategies (PROPHET) was to examine the healthcare costs of human immunodeficiency virus (HIV)–infected persons in Germany treated with different antiretroviral therapy (ART) strategies and to identify variables associated with high costs. Methods The setting was a 24-month prospective multicenter observational cohort study in a German HIV-specialized care setting from 2014 to 2017. A microcosting approach was used for the estimation of healthcare costs. Data were obtained via electronic case report forms. The costs were calculated from both the societal and the statutory health insurance perspective. Regression models were performed that took into consideration the impact of several independent variables. Results Four hundred thirty-four patients from 24 centers throughout Germany were included. Average annual healthcare costs were €20 118 (standard deviation [SD] €6451) per patient from the societal perspective (n = 336) and €17 306 (SD €4106) from the statutory health insurance perspective (n = 292). Expenditures for the ART medication had the highest impact. Total costs declined in the second year of therapy. There was a significant association between the amount of total cost and clinical or therapeutic variables from both perspectives; a diagnosis of acquired immune deficiency syndrome (AIDS) led to higher costs as well as the chosen ART strategy. Age also increased cost from the statutory health insurance perspective. Conclusions The main cost driver of the healthcare costs for HIV-positive patients was antiretroviral drug expenses. Further variables that influenced the costs were identified. The results provide a detailed overview of the resource use of patients in the PROPHET cohort.

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.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.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 (P0.0001), CD4 ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P0.001), and time since diagnosis (P=0.007). In the multivariable binary logistic regression analysis GT3, age above 45 years and being diagnosed2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease.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.

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence and prevalence of infections with HIV, Chlamydia, Gonorrhea, Syphilis, Hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with Chlamydia/Gonorrhea and Syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Logistic regression was used to analyze risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), PrEP indication 98.6% men who have sex with men (MSM). Duration of PrEP use were 5132 py; median duration 451 days (IQR 357-488).Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for Chlamydia, 23.7/100py for Gonorrhea, 10.1/100py for Syphilis and 55.4/100py for any STI and decreased significantly. 65.5% of Syphilis, 55.6% of Chlamydia and 50.1% of Gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for Chlamydia/Gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for Chlamydia/Gonorrhea and Syphilis.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were likely influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Background Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. Methods To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. Results Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015–2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. Conclusions HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.

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.

Background Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination bictegravir plus emtricitabine and tenofovir alafenamide (BIC/F/TAF) has shown comparable NPAE rates but some favourable patient-reported outcomes in RCTs compared with DTG. We were interested in its neuropsychiatric tolerability in clinical practice. Methods All patients starting BIC/F/TAF from June 2018 in a single centre (two subcentres) were followed retrospectively. Discontinuation rates due to any AEs and NPAEs were compared with those of patients initiating DTG-based regimens. Results As of May 2019, a total of 943 patients (852 males, 76 females, 15 transgender and gender diverse) initiated BIC/F/TAF outside RCTs. After a median follow-up of 6.2 months, 50 (5.3%) and 31 (3.3%) patients had discontinued BIC/F/TAF due to any AEs or to NPAEs, respectively. In multivariate analysis, a pre-existing depression and subcentre remained predictive for NPAEs, but not age, gender, ethnicity or prior DTG-related AEs. Compared with 1,043 patients treated with DTG-based regimens, the estimated NPAE-related discontinuation rate with BIC/F/TAF was comparable during the first 6 months ( P=0.36). Cross-intolerance was low, and only 5/55 patients with prior DTG intolerability had to discontinue BIC/F/TAF due to NPAEs. Conclusions Short-term tolerability of BIC/F/TAF was comparable to DTG-containing regimens. As seen with DTG, discontinuation rates were higher than in RCTs. A pre-existing depression but also physician's awareness may have an impact on tolerability and continuation of BIC/F/TAF. In contrast, prior intolerability of DTG was of limited predictive value.

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. 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. 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. 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. Alanin-Aminotransferase (ALT)-Spiegel bei Hepatitis-C-Virus (HCV) infizierten Patienten werden durch die Krankheitsaktivität der Hepatitis C, aber auch durch Demografie, Lebensstil und Komorbiditäten beeinflusst. Direkt wirkende antivirale Agenzien (DAA) erzielen eine virologische Ausheilung in 90 % der Patienten, unabhängig von HCV-Genotyp und Fibrose-Stadium. Dies ermöglicht festzustellen, welche Faktoren ALT-Spiegel vor und nach der Eliminierung von HCV determinieren. Die GECCO-Kohorte ist eine prospektive Kohorte aus HCV- und HIV/HCV-infizierten Patienten, die in neun deutschen Zentren mit DAA behandelt wurden. Wir analysierten alle konsekutiven Patienten mit anhaltender virologischer Remission (SVR) in Woche 12 (SVR12) und/oder 24. Eine normale ALT wurde definiert als ≤ 35 U/L, unabhängig vom Geschlecht. Zu Studienbeginn hatten 1477 von 1774 Patienten (83 %) eine ALT 35 U/L, und 297 (17 %) zeigten eine ALT ≤ 35 U/L. Baseline ALT 35 U/L war unabhängig mit männlichem Geschlecht, höherem Body-Mass-Index (BMI), Leberzirrhose und fehlender Opiat-Substitution assoziiert. Nach der SVR normalisierten 80 % der Patienten die ALT, und sogar Patienten mit niedriger Baseline-ALT senkten die ALT-Werte weiter. ALT blieb jedoch nach SVR12 bei 15 % (221/1477) bei 35 U/L. In einer multivariaten Analyse war ALT 35 U/L nach SVR12 mit männlichem Geschlecht, höherem BMI, Leberzirrhose, Ausgangs-ALT, HCV-Genotyp 2 und jüngerem Alter assoziiert. Adipositas, Zirrhose und ALT waren bei Patienten mit normaler ALT zu Studienbeginn ebenfalls unabhängige Faktoren, die mit ALT 15 U/L bei SVR12 assoziiert waren. Männliches Geschlecht, fortgeschrittene Leberfibrose und Adipositas sind Hauptrisikofaktoren für das Fehlen von ALT Normalisierung und/oder ALT Rückgang nach SVR, was auf eine Fettleber als relevante Komorbidität bei Hepatitis C hinweist.

Introduction Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. Methods Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. Results Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. Conclusions This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

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.

Background Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for men-who-have-sex-with-men (MSM). The high cost of PrEP has until recently been a primary barrier to its use. In 2017, generic PrEP became available, reducing the costs by 90%. Aim Our objective was to assess cost-effectiveness and costs of introducing PrEP in Germany. Methods We calibrated a deterministic mathematical model to the human immunodeficiency virus (HIV) epidemic among MSM in Germany. PrEP was targeted to 30% of high-risk MSM. It was assumed that PrEP reduces the risk of HIV infection by 85%. Costs were calculated from a healthcare payer perspective using a 40-year time horizon starting in 2018. Results PrEP can avert 21,000 infections (interquartile range (IQR): 16,000–27,000) in the short run (after 2 years scale-up and 10 years full implementation). HIV care is predicted to cost EUR 36.2 billion (IQR: 32.4–40.4 billion) over the coming 40 years. PrEP can increase costs by at most EUR 150 million within the first decade after introduction. Ten years after introduction, PrEP can become cost-saving, accumulating to savings of HIV-related costs of EUR 5.1 billion (IQR: 3.5–6.9 billion) after 40 years. In a sensitivity analysis, PrEP remained cost-saving even at a 70% price reduction of antiretroviral drug treatment and a lower effectiveness of PrEP. Conclusion Introduction of PrEP in Germany is predicted to result in substantial health benefits because of reductions in HIV infections. Short-term financial investments in providing PrEP will result in substantial cost-savings in the long term.

HIV infection has evolved from a fatal to a treatable condition, leading to an increase in the rate of elderly People Living with HIV (PLWH). However, little is known about the psychosocial burden of elderly PLWH. Thus, the aim of this longitudinal multi-center cohort study was to investigate whether elderly PLWH experience more anxiety and depression and reduced health related quality of life (HRQOL) compared to elderly patients with other chronic conditions. PLWH were compared to diabetes patients (DM) and patients with minor health conditions (MHC), e.g. patients with hypertension or allergic conditions. All patients were over 50 years old. Anxiety and depression (HADS) as well as HRQOL (SF-36) were assessed at baseline and after 12 months. 218 PLWH, 249 DM and 254 MHC were included. At baseline, the study groups did not differ in anxiety, depression, and physical HRQOL. However, PLWH indicated lower mental HRQOL than DM and MHC patients (p = 0.001). We did not obtain any moderating effects showing a differential effect of patient characteristics on anxiety, depression, and HRQOL in the three patient groups. At follow-up, the level of anxiety, depression, and HRQOL did not change significantly. The prevalence of anxiety ranged between 27 and 35%, and that of depression between 17 and 28%. Thus, the results of our investigation tentatively suggest that the psychosocial adaptation to HIV among elderly PLWH resembles those of other chronic diseases. There may be some subtle impairments, though, as PLWH experienced lower mental HRQOL.

Background Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. Aim To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. Methods In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. Results A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. Conclusion Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.

To examine current risk behavior, awareness, experience, and attitudes towards pre-exposure-prophylaxis (PrEP), and to estimate a potential impact on the prevention of HIV transmission among HIV-negative MSM in Germany. PrEP was not officially licensed at the time of survey. Web-based questionnaire from 03–06/2016. Potential participants were informed through social media, flyers, and advertisements. Risk contacts were defined as unprotected sexual intercourse under the influence of recreational drugs in the past 6 months. In total, 1208 subjects participated, 342 subjects were excluded for being HIV-infected or non-MSM, leaving 866 subjects to be evaluated in this analysis. Mean age was 37.0 ± 10.4 years. 593 participants (68.5%) were tested for HIV within the past 12 months. A total of 206 STDs in the past 6 months were reported by 144 (16.6%). Aware of PrEP was 748 (86.4%) respondents, while 65.1% reported willingness to use it. Risk behavior was significantly associated with higher PrEP acceptance (OR 2.90, 95% CI 2.14–3.90), as was a history of STDs (OR 1.85, 95% CI 1.17–2.91). The use of condoms would forgo 52.3% of subjects if taking PrEP. Sixty-five respondents (7.5%) reported PrEP use. Only 19 (29.2%) had accessed PrEP under medical supervision. PrEP use was reported by 14.8% with > 5 risk contacts in the past 6 months, compared to 6.3% with one risk contact (p

Current hepatitis C virus (HCV) treatment guidelines recommend treating HCV/human immunodeficiency virus (HIV)-coinfected individuals similar to HCV-monoinfected individuals. Recently inferior response rates to direct acting antiviral (DAA) therapy in HCV/HIV coinfection have been reported. Our German hepatitis C cohort (GECCO) cohort data show that coinfected patients with liver cirrhosis are less likely to achieve viral eradication.

There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. 342 chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37.1%], 38 HCV/HIV co-infected patients [11.1%]). SVR12 rates in the “intention-to-treat” analysis were as follows: sofosbuvir/ribavirin 69.4% (75/108), sofosbuvir/peginterferon/ribavirin 80.6% (58/72), sofosbuvir/daclatasvir ± ribavirin for 12 weeks 88.3% (53/63), sofosbuvir/daclatasvir ± ribavirin for 24 weeks 79.3% (23/29), sofosbuvir/ledipasvir ± ribavirin for 12 weeks 71.4% (10/14) and sofosbuvir/ledipasvir ± ribavirin for 24 weeks 86.7% (26/30). Forty patients were lost to follow-up, 23 patients had a relapse, 4 patients stopped treatment prematurely and 1 patient died. Female sex (P = 0.038) and treatment with two different DAAs (P = 0.05) were predictors for SVR12 in the multivariate analysis. In conclusion, sofosbuvir/daclatasvir ± ribavirin for 12 weeks and sofosbuvir/ledipasvir ± ribavirin for 24 weeks are effective for the treatment of HCV genotype 3 infected patients including cirrhotic, treatment-experienced or HIV/HCV co-infected patients. This article is protected by copyright. All rights reserved

Background HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon (IFN) therapy has been shown to decrease cholesterol even further. With the availability of second-generation direct-acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation. Methods Prospective German multicentre cohort on HCV- and HIV–HCV-infected patients treated with direct-antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy. Wilcoxon test corrected for multiple testing was used. Results For the analysis, 520 patients with chronic hepatitis C were available. Patients with chronic hepatitis C were treated as follows: sofosbuvir (SOF)/pegylated IFN (PEG-IFN)/ribavirin (RBV; HCV=34, HIV–HCV=36), SOF/ RBV (HCV=47, HIV–HCV=16), SOF/simeprevir (HCV=9, HCV–HIV=2), SOF/daclatasvir +/- RBV (HCV=27, HIV–HCV=47), SOF/ledipasvir +/- RBV (HCV=147, HCV–HIV=100) and ombitasvir/paritaprevir/ritonavir +/-dasabuvir +/- RBV (2D, HCV=2, HCV–HIV=6; 3D, HCV=39, HCV–HIV=8). On treatment there was a statistically significant increase in total cholesterol for any IFN-free DAA regimen, which was maintained after end of therapy. Changes of total cholesterol were driven by changes in low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol remained unchanged. In contrast, total cholesterol decreased on SOF/PEG-IFN/RBV and increased after end of therapy above baseline levels. Triglycerides increased during treatment with SOF/PEG-IFN/RBV, but not on DAA-only regimens. Conclusions Suppressing and eliminating HCV with IFN-free DAA regimens increased cholesterol levels, but had no effect on triglycerides. In contrast IFN-based therapy decreased cholesterol and increased triglycerides during treatment and led to increases in cholesterol after achieving sustained virological response.

Background Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. Methods Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. Results Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. Conclusions SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting.

The aims of this study were to estimate the expenditure for HIV-care in Germany and to identify variables associated with resource use. We performed an 18-month prospective multi-center study in an HIV specialized ambulatory care setting from 2006 to 2009. Patients were eligible for study participation if they (1) were HIV-positive, (2) were ≥18 years of age, (3) provided written consent and (4) were not enrolled in another clinical study; 518 patients from 17 centers were included. Health care costs were estimated following a micro-costing approach from two perspectives: (1) costs incurred to society in general, and (2) costs incurred to statutory health insurance. Data were obtained using questionnaires. Several empirical models for identifying the relationship between health care costs and independent variables, including age, gender, route of transmission and CD4 cell count at baseline, were developed. Average annual health care costs were €23,298 per patient from the societal perspective and €19,103 from the statutory health insurance perspective. Most expenses are caused by antiretroviral medication (80 % of the total and 89 % of direct costs), while hospital costs represented 7 % of total expenditure. A statistically significant association was found between health care costs and clinical variables, with higher CD4 count and female gender generating lower costs, while increased antiretroviral experience and injection drug use led to higher expenditures (P

Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.

The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500-mg filmcoated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of antiretroviral therapy (ART)-naive and pretreated but protease inhibitor (PI)-naive patients. This was a multicenter, prospective, open-label, 48-week observational cohort study. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. Efficacy assessments included changes in the proportion of patients with HIV-1 RNA

Hepatitis C virus (HCV)/human immunodeficirency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-α. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P < 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P < 0.05) and chronic (66% versus 33%; P < 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd′s ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. Conclusion: Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation. (HEPATOLOGY 2007.)

To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use. A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF. The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance. The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk

Background: Data on the relative contribution of HIV-infection to aging and age-related diseases remains inconclusive, and the total burden of disease has not been compared to other chronic diseases associated with premature aging. The purpose of this study was to investigate aging with HIV-infection and to compare it to aging with diabetes mellitus (DM) type 2 and aging without severe chronic disease. Methods: This was a prospective multi-center cohort study evaluating differences in the total burden of disease between different groups of older patients (≥ 50 years). HIV-infected patients were compared to HIV-negative patients with DM type 2 and to a control group of patients without severe chronic disease. Physical constitution and activity, symptoms of aging, cardiovascular risk profile and comorbidities were analyzed. Clinical variables and patient questionnaires were assessed during 18 months follow-up. Results: Among 761 participants (255 HIV, 249 DM, and 257 controls), weakness was most frequently found in HIV-infected patients. The perceived severity of symptoms of aging was significantly higher in patients with HIVinfection or DM than in the control group. Several comorbidities such as renal, neurological and cardiovascular disorders were more common in patients with HIV-infection or DM than in the control group. After adjusting for smoking and non-modifiable risk factors, the prevalence odds of a high cardiovascular risk remained markedly increased for patients with DM and, to a lesser extent, also for patients with HIV-infection. Malignancy incidence rates were highest in HIV-infected patients, followed by patients with DM and lowest in the control group. Conclusions: This large cohort study in aging patients showed a considerable burden of disease associated with antiretrovirally treated HIV-infection as well as DM when compared to a control population without severe chronic disease – reflecting the need for specific prevention strategies and screening tools.

Background Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. Methods Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. Results Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. Conclusions Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.

CRANIum, a cross-sectional epidemiology study in Western Europe and Canada, was conducted to describe and compare the prevalence of a positive screen for neurocognitive impairment (NCI), depressive symptoms, and anxiety in an HIV-positive population either receiving combination antiretroviral therapy (cART) or who were naive to antiretroviral therapy (ART). HIV-positive patients ≥18 years of age attending a routine medical follow-up visit and able to complete the designated screening tools were eligible for study inclusion. The Brief Neurocognitive Screen was used to assess NCI; depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale. The evaluable patient population (N = 2863) included 1766 men (61.7%) and 1096 (38.3%) women. A total of 1969 patients were cART-experienced (68.8%), and 894 were ART-naive (31.2%). A positive screen for NCI was found in 41.5% of patients (cART-experienced, 42.5%; ART-naive, 39.4%; p = 0.12). A positive screen for depressive symptoms was found in 15.7% of patients (cART-experienced, 16.8%; ART-naive, 13.3%; p = 0.01), whereas 33.3% of patients screened positive for anxiety (cART-experienced, 33.5%; ART-naive, 32.8%; p = 0.71). A greater percentage of women compared with men screened positive for NCI (51.78% vs. 35.1%; p < 0.0001) and depressive symptoms (17.9% vs. 14.3%; p = 0.01). These data suggest that neurocognitive and mood disorders remain highly prevalent in HIV-infected patients. Regular mental health screening in this population is warranted.

A retrospective chart analysis of 66 human immunodeficiency virus type 1 (HIV-1)— infected patients whose treatment was switched from stavudine to tenofovir without any other treatment changes was conducted. The mean total cholesterol values decreased significantly within 3 months after the tenofovir substitution and remained significantly less than baseline values during 18 months of follow-up (mean decrease, 36 mg/dL; P =.002). Regimens containing tenofovir provided effective control of HIV-1 infection, with stable CD4 + cell counts and continued suppression of plasma HIV-1 level following the treatment switch from stavudine.

There is increasing evidence that shigellosis is a predominantly sexually transmitted disease among men who have sex with men (MSM) and that infection with the human immunodeficiency virus (HIV) is a risk factor for shigellosis.Retrospective analysis of antibiotic resistance profiles of Shigella species isolated from stool specimens of patients presenting with diarrhea from January 2010 to July 2012 in three German outpatient clinics specialized in HIV care.Among 79 cases of Shigella sonnei, 56 occurred in HIV-infected MSM, while 23 were observed in HIV-negative MSM. High resistance rates (90%) were found for doxycycline, tetracycline, aminoglycosides, all cephalosporins of first and second generations tested, and trimethoprim/sulfamethoxazole. In total, 54% of cases were resistant to ciprofloxacin. Compared to negative subjects, HIV-infected MSM had a significantly higher rate of quinolone resistance. For ciprofloxacin, the resistance rates were 66 versus 24%, respectively (p = 0.0016). Individual resistance patterns did not indicate that this was due to a limited outbreak. Rates of resistance to other antibiotics than quinolones showed no differences between HIV-infected and HIV-negative cases. No resistance was found for carbapenems or newer cephalosporins such as ceftriaxone.The high rates of S. sonnei isolates resistant to quinolones and other traditional antibiotics are of concern. Innovative prevention efforts are urgently needed. The empirical use of quinolones in HIV-infected patients presenting with S. sonnei infection is no longer recommended.

Hitherto, studies on highly active antiretroviral therapy (HAART) initiation have shown partly inconsistent results. Our study investigated the clinical course and course of immune status after HAART initiation at CD4-cell-count/μl of treated patients between 250 and 349 (group 1), compared to 350-449 (group 2), on the basis of the cohort of the Competence Network for HIV/AIDS (KompNet cohort).Patients had to be HAART-naïve. Medication had to start at the earliest in 1996, being at least triple combination therapy. The primary endpoints of death, first AIDS-defining illness and first drop of CD4-cell-count/μl below 200 were evaluated as censored event times between the initiation of HAART (t (0)) and the date of the first event/date of last observation. Probabilities of event-free intervals since t (0) were calculated by Kaplan-Meier estimation, compared by logrank tests. The results were adjusted for confounders using Cox regression. Additionally, incidences were estimated.A total of 822 patients met the inclusion criteria (group 1: 526, group 2: 296), covering 4,133 patient years (py) overall. In group 1, 0.64 death cases/100 py were found, with the corresponding vale being 0.17 in group 2. In group 1, 1.38 AIDS-defining events/100 py occurred, whereas it was 0.78 in group 2. In group 1, 2.64 events of first drop of CD4-cell-count/μl below 200 occurred per 100 py, compared to 0.77 in group 2. Kaplan-Meier estimations showed borderline significant differences regarding death (p = 0.063), no differences regarding first AIDS-defining illness (p = 0.148) and distinct differences regarding the first drop of CD4-cell-count/μl below 200 (p = 0.0004).The results gave a strong hint for a therapy initiation at higher CD4-cell-count/μl regarding the outcome of death in treated patients. A distinct benefit was shown regarding the first decline of CD4-cell-count/μl below 200.

Poster presentation: Purpose of the study The aim of the Rainbow Cohort is to assess the tolerability and efficacy of initiating treatment with, or switching treatment to saquinavir (SQV) 500 mg film-coated tablet formulation. We present the final 48-week subgroup analysis of antiretroviral therapy (ART)-naive patients. ...

Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic.Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy.Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks.Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.