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Background: Despite the potentially accompanying negative clinical, epidemiologic, and health economic effects, a large proportion of persons living with the human immunodeficiency virus (HIV) are diagnosed late. Internationally, numerous diseases are known to be HIV indicator diseases. Adequate HIV testing in the presence of HIV indicator diseases could help to diagnose unknown HIV infections earlier. The objective of the HeLP study is to validate published HIV indicator diseases for the German setting and to identify guidelines in terms of these indicator diseases in order to reduce knowledge gaps and increase HIV testing when HIV indicator diseases are diagnosed. Methods: A mixed methods approach is used. In a first step, published HIV indicator diseases will be identified in a systematic literature review and subsequently discussed with clinical experts regarding their relevance for the German setting. For the validation of selected indicator diseases different data sets (two cohort studies, namely HIV-1 seroconverter study & ClinSurv-HIV, and statutory health insurance routine data) will be analyzed. Sensitivity analyses using different time periods will be performed. Guidelines of HIV indicator diseases validated in the HeLP study will be reviewed for mentioning HIV and for HIV testing recommendations. In addition, semi-standardized interviews (followed by a free discussion) with guideline creators will identify reasons why HIV testing recommendations were (not) included. Subsequently, a random sample of physicians in medical practices will be surveyed to identify how familiar physicians are with HIV testing recommendations in guidelines and, if so, which barriers are seen to perform the recommended tests in everyday care. Discussion: The HeLP-study adopts the challenge to validate published HIV indicator diseases for the German setting and has the potential to close a knowledge gap regarding this objective. This has the potential to improve targeted HIV testing for patients with HIV indicator diseases and consequently lead to earlier HIV diagnosis. Trial registration: DRKS00028743 [ABSTRACT FROM AUTHOR]

Purpose: Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. Methods: HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. Results: The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. Conclusions: PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM. Methods: From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months. Results: Among 1017 participants with median age 33 (interquartile range 28–39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing. Conclusion: Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objectives: HIV Pre‐Exposure prophylaxis (PrEP) is a strategy to reduce HIV transmission in people at risk. Aim of this first German‐Austrian PrEP guideline is to provide professional guidance on: when and in whom to use PrEP, recommended laboratory tests before and while on PrEP, selection of drugs, prevention of adverse events as a consequence of missing accompanying medical care, and general handling of PrEP in adults and adolescents. Methods: Commented summary of of the S2k PrEP consensus guidelines released by the German and Austrian HIV medical societies to highlight the key recommendations of the guidelines. Content: Detailed information about effectiveness of PrEP, when and in whom to use PrEP, as well as about additional monitoring of HIV PrEP are included in the HIV PrEP guidelines. Therewith detailed guidance for people being involved in PrEP counseling and associated care is provided. [ABSTRACT FROM AUTHOR]

Objectives: Rectal infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae (CT/NG) are common in men who have sex with men (MSM) and are linked to HIV transmission. However, rectal CT/NG infections are often asymptomatic and it is not known how they contribute to HIV transmission. We assessed clinical and cytological signs of inflammation as well as rectal HIV-RNA in HIV-infected MSM with and without CT/NG infection.Methods: 112 HIV-positive MSM with or without rectal symptoms and with or without antiretroviral therapy who underwent high-resolution anoscopy (HRA) at the proctological outpatient centre of the University Hospital Essen, Germany, between November 2013 and February 2014 were included in this cross-sectional study. During the examination, rectal swabs for the assessment of CT/NG, HIV-RNA and inflammatory cells (granulocytes, lymphocytes, histiocytes) were collected. 110 patients were assessed according to the study protocol, and no imputation of missing data was performed.Results: Rectal infections with CT or NG were detected in 17 participants, and 4 participants were coinfected. Only symptomatic CT/NG infections (8/17) showed signs of inflammation in HRA. Symptomatic CT/NG infections were also associated with the detection of lymphocytes and histiocytes in rectal cytology (both P<0.001). In contrast, asymptomatic CT/NG infections neither resulted in clinical nor cytological signs of inflammation. Rectal HIV-RNA was undetectable in all participants with rectal CT/NG infections who received combined antiretroviral therapy (ART) when plasma HIV-RNA was below the limit of detection (n=13). Besides rectal CT/NG infections, syphilis (n=4) and HPV-associated lesions (n=37) were frequently detected, and proctological symptoms were associated with simultaneous infection with ≥2 STDs.Conclusions: Only symptomatic but not asymptomatic rectal infections with CT and/or NG were associated with clinical and cytological signs of inflammation. Rectal HIV shedding was not promoted by CT/NG infections in patients receiving ART with suppressed plasma HIV-RNA.Trial Registration Number: UTN: U1111-1150-4804. German Clinical Trials Register (DRKS): DRKS00005468. [ABSTRACT FROM AUTHOR]

Overall survival ( OS) of patients with acquired immunodeficiency syndrome ( AIDS)-related Burkitt lymphoma ( BL), diffuse large B-cell lymphoma ( DLBCL) and plasmablastic lymphoma ( PBL) was analysed in the German AIDS-related-Lymphoma-Cohort-Study. Of 291 patients prospectively included between January 2005 and December 2012, 154 had DLBCL, 103 BL and 34 PBL. Two-year OS rates were similar between BL (69%) and DLBCL patients (63%) but lower for PBL patients (43%). Intermediate (Hazard ratio [ HR] 4·1 95% confidence interval [ CI] 1·98-8·49) or high ( HR 4·92 95% CI 2·1-11·61) International Prognostic Index, bone marrow involvement ( HR 1·69 95% CI 1·00-2·84) and PBL histology ( HR 2·24 95% CI 1·24-4·03) were independent predictors of mortality. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the number of people living with HIV receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using the available numbers of antiretroviral drug prescriptions and treatment data from the ClinSurv HIV cohort (CSH). Methods: The CSH is a multi-centre, open, long-term observational cohort study with an average number of 10.400 patients in the study period 2006-2013. ART has been documented on average for 86% of those CSH patients and medication history is well documented in the CSH. The antiretroviral prescription data (APD) are reported by billing centres for pharmacies covering >99% of nationwide pharmacy sales of all individuals with statutory health insurance (SHI) in Germany (∼85%). Exactly one thiacytidine-containing medication (TCM) with either emtricitabine or lamivudine is present in all antiretroviral fixed-dose combinations (FDCs). Thus, each daily dose of TCM documented in the APD is presumed to be representative of one person per day receiving ART. The proportion of non-TCM regimen days in the CSH was used to determine the corresponding number of individuals in the APD. Results: The proportion of CSH patients receiving TCMs increased continuously over time (from 85% to 93%; 2006-2013). In contrast, treatment interruptions declined remarkably (from 11% to 2%; 2006-2013). The total number of HIV-infected people with ART experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to 54,000 (95% CI 53,000-55,500) over the observation period (including 16.3% without SHI and persons who had interrupted ART). An average increase of approximately 2,900 persons receiving ART was observed annually in Germany. Conclusions: A substantial increase in the number of people receiving ART was observed from 2006 to 2013 in Germany. Currently, the majority (93%) of antiretroviral regimens in the CSH included TCMs with ongoing use of FDCs. Based on these results, the future number of people receiving ART could be estimated by exclusively using TCM prescriptions, assuming that treatment guidelines will not change with respect to TCM use in ART regimens. [ABSTRACT FROM AUTHOR]

The high number of Turkish immigrants in the German state North-Rhine Westphalia (NRW) compelled us to look for HIV-infected patients with Turkish nationality. In the AREVIR database, we found 127 (107 men, 20 women) Turkish HIV patients living in NRW. In order to investigate transmission clusters and their correlation to gender, nationality and self-reported transmission mode, a phylogenetic analysis including pol gene sequences was performed. Subtype distribution and the number of HIV drug resistance mutations in the Turkish patient group were found to be similar to the proportion in the non-Turkish patients. Great differences were observed in self-reported mode of transmission in the heterosexual Turkish male subgroup. Neighbour-joining tree of pol gene sequences gave indication that 59% of these reported heterosexual transmissions cluster with those of men having sex with men in the database. This is the first study analysing HIV type distribution, drug resistance mutations and transmission mode in a Turkish immigrant population. [ABSTRACT FROM AUTHOR]

• The average SARS-CoV-2 seroprevalence in healthcare workers of a a tertiary hospital, University Hospital Essen, Germany was 1.6 % in the period between March to April 2020. • The local hygiene standards seem to be effective to prevent patient-to-staff virus transmission at the designated COVID-19 units wards. • Awareness for COVID-19 infections is crucial even in non−COVID-19 wards. The novel coronavirus SARS-CoV-2 is associated with a severe respiratory manifestation, COVID-19, and presents a challenge for healthcare systems worldwide. Healthcare workers are a vulnerable cohort for SARS-CoV-2 infection due to frequent and close contact to patients with COVID-19. Serum samples from 316 healthcare workers of the University Hospital Essen, Germany were tested for SARS-CoV-2-IgG antibodies. A questionnaire was used to collect demographic and clinical data. Healthcare workers were grouped depending on the frequency of contact to COVID-19 patients in high-risk-group (n = 244) with daily contact to known or suspected SARS-CoV-2 positive patients, intermediated-risk-group (n = 37) with daily contact to patients without known or suspected SARS-CoV-2 infection at admission and low-risk-group (n = 35) without patient contact. In 5 of 316 (1.6 %) healthcare workers SARS-CoV-2-IgG antibodies could be detected. The seroprevalence was higher in the intermediate-risk-group vs. high-risk-group (2/37 (5.4 %) vs. 3/244 (1.2 %), p = 0.13). Four of the five subject were tested negative for SARS-CoV-2 via PCR. One (20 %) subject was not tested via PCR since he was asymptomatic. The overall seroprevalence of SARS-CoV-2 in healthcare workers of a tertiary hospital in Germany is low (1.6 %). The data indicate that the local hygiene standard might be effective. [ABSTRACT FROM AUTHOR]

IntroductionDespite increased use of pre-exposure prophylaxis (PrEP) in Germany, HIV infection rates are not declining and little is known about how this prevention method affects the prevalence of sexually transmitted infections (STI) among men who have sex with men (MSM).AimWe studied, in a large multicentre cohort, STI point prevalence, co-infection rates, anatomical location and influence of PrEP.MethodsThe BRAHMS study was a prospective cohort study conducted at 10 sites in seven major German cities that enrolled MSM reporting increased sexual risk behaviour. At screening visits, MSM were tested for Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum (TP) , and given a behavioural questionnaire. With binomial regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the association of PrEP and STI.ResultsWe screened 1,043 MSM in 2018 and 2019, with 53.0% currently using PrEP. At screening, 370 participants (35.5%) had an STI. The most common pathogen was MG in 198 (19.0%) participants, followed by CT (n = 133; 12.8%), NG (n = 105; 10.1%) and TP (n = 37; 3.5%). Among the 370 participants with at least one STI, 14.6% (n = 54) reported STI-related symptoms. Infection prevalence was highest at anorectal site (13.4% MG, 6.5% NG, 10.2% CT). PrEP use was not statistically significant in adjusted models for STI (PR: 1.10; 95% CI: 0.91-1.32), NG/CT, only NG or only CT.ConclusionsPrevalence of asymptomatic STI was high, and PrEP use did not influence STI prevalence in MSM eligible for PrEP according to national guidelines.

Broad administration of combined antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality of the HIV-infection and substantially improved the life expectancy of people living with HIV (PLWH). PLWH, who are effectively treated with an ART, are considered to be unable to transmit HIV. The standard of care is usually an antiretroviral single tablet regimen. Since 2015 the Robert Koch Institute has reported a slight decrease in the rate of recently diagnosed HIV-infections in Germany, but the proportion of late presenters (initial diagnosis in advanced stages of infection) has remained consistently high at around 32 % since 2005. HIV-infections have not been diagnosed in 10,800 PLWH so far. In comparison to the general population PLWH suffer more frequently from skin diseases. Depending on the stage of immunodeficiency, untreated PLWH develop HIV indicator diseases of the skin and the mucocutaneous membranes. Knowledge of these diseases facilitates the selection of individuals who should be offered HIV testing. Early diagnosis of HIV-infections allows early introduction of the ART, prevents the spread of HIV and reduces the mortality rates and treatment costs associated with late diagnosis. HIV is a predominantly sexually transmitted infection. Through focused sexual anamnesis and the diagnosis of HIV indicator diseases and other sexually transmitted infections, dermatovenereologists in particular may be able to identify previously undiagnosed PLWH and persons with an increased risk of HIV infection, enabling initiation of ART in the former and pre-exposure prophylaxis counseling in the latter., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Teledermatology addresses the problems associated with the lack of specialists and the often long waiting time for an appointment with a dermatologist. The research project Online Dermatologist-AppDoc enables a fast anonymous expert opinion and was approved on 22 October 2018 by the Landesärztekammer Baden-Württemberg for 2 years as a model project., Objectives: The aim of the present work is the presentation of the first real healthcare data for German teledematology within the framework of the external quality assurance of the model project Online Dermatologist-AppDoc., Materials and Methods: Anonymous data records submitted to Online Dermatologist-AppDoc between 21 November 2018 and 1 August 2019 were analyzed qualitatively and quantitatively at the Department of Dermatology of the University Hospital Essen. In addition to the evaluation of the data records submitted so far, 100 cases submitted underwent a second assessment by a board-certified dermatologist to assess concordance., Results: A total of 1364 cases (60.4% men, 39.6% women) were included in the current first external scientific evaluation. In 90.3% of the cases, remote diagnosis was possible. The two most frequent diagnoses were different forms of eczema (n = 270) and nevi (n = 163). Almost two thirds of the patients (64.3%) could be treated teledermatologically only. The random second examination of 100 cases resulted in an agreement of the diagnosis including the differential diagnosis/diagnoses in 97% of the cases., Conclusions: The first external scientific evaluation of the teledermatological model project Online Dermatologist-AppDoc indicates that the reduction of spatial and temporal barriers of a dermatological examination as well as the teledermatological triage have been so far successful.

Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving., Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data., Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR)., Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

Pre-Exposure Prophylaxis (PrEP) has been widely accepted as an effective method to prevent HIV infections, but high costs precluded a widespread use in Germany. A novel distribution pathway of tenofovir-disoproxil fumarate and emtricitabine PrEP was implemented, which reduced monthly PrEP costs by 16-fold in Germany. Over a period of 6 months, we recorded prescription data, demographics, and sexual behavior of PrEP users, including self-reported sexually transmitted infections (STIs), alcohol and drug use. Within a month, prescriptions almost doubled from 585 to 1,009 and reached a cumulative number of 6,059 at the end of the 6-month observation period. Extrapolation of the data suggests an estimated maximal number of PrEP users of the order of 10,000. PrEP users demonstrated to be a population of well-educated men (407/686) who have sex with men (629/686), median age 38 (range:18-71), and of German descent (571/686). The majority used PrEP to compensate for risk of HIV infection when having condomless anal intercourse (372/686). At start of PrEP implementation, the majority perceived their own risk to acquire HIV as none to medium (78.6%; n  = 539), while only a subset (18.8%; n  = 129) considered themselves to be at high or very high risk for HIV infection. In contrast, within the last 6 months, 28.4% of the PrEP users had an STI diagnosis and over 70% had condomless anal intercourse with more than 6 partners. Taken together, our data from PrEP implementation in Germany demonstrate a large uptake once it became affordable in individuals who wish to compensate for HIV risk when having condomless anal intercourse.

Objectives: Rectal infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae (CT/NG) are common in men who have sex with men (MSM) and are linked to HIV transmission. However, rectal CT/NG infections are often asymptomatic and it is not known how they contribute to HIV transmission. We assessed clinical and cytological signs of inflammation as well as rectal HIV-RNA in HIV-infected MSM with and without CT/NG infection., Methods: 112 HIV-positive MSM with or without rectal symptoms and with or without antiretroviral therapy who underwent high-resolution anoscopy (HRA) at the proctological outpatient centre of the University Hospital Essen, Germany, between November 2013 and February 2014 were included in this cross-sectional study. During the examination, rectal swabs for the assessment of CT/NG, HIV-RNA and inflammatory cells (granulocytes, lymphocytes, histiocytes) were collected. 110 patients were assessed according to the study protocol, and no imputation of missing data was performed., Results: Rectal infections with CT or NG were detected in 17 participants, and 4 participants were coinfected. Only symptomatic CT/NG infections (8/17) showed signs of inflammation in HRA. Symptomatic CT/NG infections were also associated with the detection of lymphocytes and histiocytes in rectal cytology (both P<0.001). In contrast, asymptomatic CT/NG infections neither resulted in clinical nor cytological signs of inflammation. Rectal HIV-RNA was undetectable in all participants with rectal CT/NG infections who received combined antiretroviral therapy (ART) when plasma HIV-RNA was below the limit of detection (n=13). Besides rectal CT/NG infections, syphilis (n=4) and HPV-associated lesions (n=37) were frequently detected, and proctological symptoms were associated with simultaneous infection with ≥2 STDs., Conclusions: Only symptomatic but not asymptomatic rectal infections with CT and/or NG were associated with clinical and cytological signs of inflammation. Rectal HIV shedding was not promoted by CT/NG infections in patients receiving ART with suppressed plasma HIV-RNA., Trial Registration Number: UTN: U1111-1150-4804. German Clinical Trials Register (DRKS): DRKS00005468., Competing Interests: Competing interests: JS reports grants from the German Federal Ministry of Health (BMG), during the conduct of the study; employee of Janssen Cilag, September 2014 until September 2017, and employee of Novartis Pharma AG since October 2017, outside the submitted work. JV reports personal fees from Abbott, personal fees from Roche, grants and personal fees from Janssen, personal fees from Siemens and personal fees from BMS, outside the submitted work. DS reports personal fees from Amgen, GSK, BMS, Novartis, Roche, Amgen, Merck, AstraZeneca, Merck Serono and Pfizer, outside the submitted work. SE reports personal fees from Gilead, personal fees from MSD, personal fees from Janssen, personal fees from ViiV, personal fees from AbbVie, grants from Gilead, grants from ViiV, grants from MSD and grants from Janssen, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate., (Copyright © 2018 Ferrata Storti Foundation.)

Background: HIV infection is a risk factor for the development of Herpes zoster (HZ) and its complications. Prior to antiretroviral therapy (ART), HZ incidence in HIV-infected individuals ranged from 2.9-5.1/100 person-years. There is limited evidence for the impact of ART on HZ occurrence among HIV-infected adults. We analysed the incidence of, and risk factors for, HZ in a large cohort of German HIV-positive patients., Methods: The study population was taken from the German KompNet cohort, a nationwide multicenter HIV cohort study. The study population was defined by age (≥ 18 years), year of first positive HIV diagnosis, CD4 values ± 6 months from HIV diagnosis (t0), and month of HZ diagnosis. Incidences were estimated using a Poisson distribution, and uni- and multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for developing an initial HZ episode. Independent variables were sex, age at HIV diagnosis, route of HIV transmission, ART status, CD4 count before HZ episode, immunosuppressive medication, and mode of data documentation (retrospective or prospective)., Results: HZ incidence in the overall study population was 1.2/100 person-years. In a subset of patients for that we were able to examine risk factors the following was observed: We examined 3,757 individuals whose mean age at t0 was 38 years. Of those individuals, 96% were diagnosed with HIV in 1996 or later, with a mean observation time of 5.8 years. HZ episodes (n = 362) were recorded in 326 patients (8.7%), resulting in annual HZ incidences of 1.7/100 person-years overall, and 1.6/100 person-years for initial HZ cases. The main risk factors associated with an initial HZ episode were: not partaking in ART compared with an ART regimen containing a non-nucleoside reverse-transcriptase inhibitor (HR 0.530, p < 0.001) or a protease inhibitor (HR 0.624, p = 0.004); and lower CD4 count by 100 cells/μl (HR 0.918, p=0.001)., Conclusions: HZ incidence was 4-11-fold higher than in non HIV-infected individuals, but in our study HZ incidences were lower than in previous studies relating to HIV-positive patients. We showed that ART is an important protective factor for HZ episodes.

Background: Recent studies suggest a rising rate of cardiovascular disease (CVD) in HIV-infected subjects. Although most countries have an aging HIV-infected population, there remains a lack of knowledge about associated cardiovascular diseases., Methods: This ongoing prospective multicentre observational cohort study aims to elucidate CVD prevalence in HIV-infected outpatients by standardized non-invasive cardiovascular screening. Cardiovascular and coronary risk was calculated using Framingham risk scores., Results: 803 HIV-infected subjects (mean age 44.2 years, female 16.6 %) were included. The prevalence of CVD in HIV-infected subjects was 10.1 % (95 % CI 8.0-12.2 %). Aging HIV-infected patients (≥45 years, N = 348) exhibited significantly increased rates of CVD, including an elevated frequency of coronary artery disease (7.5 vs. 1.8 %, p < 0.001), myocardial infarction (6.0 vs. 1.8 %, p = 0.002) and peripheral arterial diseases (4.6 vs. 1.5 %, p < 0.017). Furthermore, aging patients exhibited a higher rate of chronic heart failure (5.2 vs. 1.5 %, p < 0.001), predominantly of ischemic etiology. In multivariate analyses, age (OR 2.05 per decade, 95 % CI 1.64-2.56), smoking (OR 5.96 per decade, 95 % CI 2.31-15.38) and advanced symptomatic HIV infection (OR 2.60 per decade, 95 % CI 1.31-5.15), were significantly associated with the prevalence of CVD. Based on the 10-year cardiovascular risk estimation, a disproportionate increase in cardiac events has to be expected in aging HIV-infected subjects in the next decades (≥45 years/<45 years 16.4 vs. 4.2 %, p < 0.001)., Conclusion: CVD in aging HIV-infected population is an increasing medical challenge. In the era of antiretroviral therapy, prevention and diagnostic strategies are essential to reduce the prevalence of CVD in HIV-infected patients.

Objective: AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers., Methods and Design: This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany., Results: Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15-0.53 and hazard ratio 0.29, 95% CI 0.16-0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25-0.93 and hazard ratio 0.47, 95% CI 0.26-0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/μl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07-0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/μl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab., Conclusion: In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.

Objectives: Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy., Methods: Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation., Results: Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months., Conclusions: These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these associations.

Background and Purpose: HIV-infected patients exhibit an increased rate of cardiac diseases, due to an elevated rate of cardiac risk factors and side effects of antiretroviral therapy. The aim of the present study was to analyze the impact of B-type natriuretic peptide (BNP) in this patient population., Patients and Methods: The HIV-HEART (HIV infection and HEART disease) study is a prospective and multicenter cohort study. Outpatients with a known HIV infection were included over a 20-month recruiting period. BNP values were determined by a standardized laboratory test at study inclusion., Results: 802 HIV-infected patients (male: 83.4%, mean age: 44.2 +/- 10.3 years) were included. The BNP concentrations (median 11.3 pg/ml; BNP < or = 100 pg/ml: 96.2%) were associated with echocardiographic parameters and with the right ventricular diameter (p = 0.02) and the systolic pulmonary arterial pressure (p = 0.01). Patients with a BNP concentration of > 50 pg/ml had a significantly higher rate of heart failure (p < 0.001), cardiomyopathy (p < 0.001), and coronary artery disease (p < 0.001)., Conclusion: The data demonstrate that BNP is suitable for the detection of cardiac disorders in HIV-infected subjects. Therefore, BNP could be an appropriate tool for a screening program for HIV-associated disorders in this patient population.

In recent years a rising incidence of syphilis has been observed, especially in the population of homosexual men. Because of altered sexual behavior in terms of increased promiscuity paralleled by decreased use of condoms and the fact that a syphilis infection increases the susceptibility to HIV coinfection, the incidence of HIV is also rising once again in this population. In patients with HIV coinfection, the course of syphilis is often atypical or dramatic. Stage-specific features suggesting coinfection include prolonged primary ulcers persisting well into the secondary stage, numerous atypical cutaneous findings in the second stage and a rapid progression from stage to stage. The diagnosis of syphilis may be more difficult because of false positive or false negative serological findings in patients with HIV coinfection. Whether or not the CNS is more often involved is this patient group has not been established by prospective studies and remains controversial. However, WHO and CDC recommendations include evaluation of the CSF in HIV-infected patients with either late syphilis or when the time course is unknown period. There is worldwide agreement on the therapy of syphilis in patients with HIV coinfection. Patients with early syphilis should be treated with 2.4 benzathine penicillin i.m. once or twice; patients with late syphilis, twice or three times. Patients presenting with clinical or serological signs of neurosyphilis require 18-24 million IU penicillin i.v. daily for at least 2 weeks.