Position statement of the German STI Society on the prophylactic use of doxycycline to prevent STIs (Doxy-PEP, Doxy-PrEP).

Over the past two decades, there has been a rise in the incidence of syphilis, particularly among men who have sex with men (MSM). This has sparked interest in studying the prophylactic use of doxycycline to prevent syphilis and other sexually transmitted infections (STIs), commonly referred to as Doxycycline Pre- or Post-Exposure Prophylaxis (Doxy-PrEP, Doxy-PEP). At the same time, demand from potential users for this preventive measure is increasing. Several randomized controlled trials have demonstrated that the prophylactic use of doxycycline in MSM and trans women using HIV pre-exposure prophylaxis (HIV-PrEP) or living with an HIV infection effectively reduces the risk of syphilis and chlamydia infections. At present, however, unresolved questions remain, particularly regarding implications of a broad implementation of prophylactic doxycycline to prevent STIs on tetracycline and other antimicrobial resistance in bacterial STIs, non-STI-related bacterial pathogens, and the microbiome. In response to the increasing demand and the challenge of balancing effectiveness, safety, and the risk of promoting antibiotic resistance, the German STI Society (DSTIG) has issued a position statement, providing specific recommendations regarding potential indications, criteria, and occasions for the use of doxycycline in STI prevention. These recommendations are based on current evidence and expert opinion.

Cholesterol-conjugated siRNAs silence gene expression in mucosal dendritic cells in cervicovaginal tissue in mice.

BACKGROUND: RNA interference (RNAi) provides a powerful way to investigate the role of genes in disease pathogenesis and modulate gene expression to treat disease. In 2018, the FDA approved patisiran, the first RNAi-based drug, hence paving the way for a novel class of RNAi therapeutics. Harnessing RNAi to inhibit vaginal HIV transmission requires effective gene silencing in immune cells, which remains difficult. Knockdown in accessible mucosal tissues may be easier than systemic gene silencing. Vaginally applied cholesterol-conjugated small interfering RNAs (chol-siRNAs) blocked herpes simplex virus transmission in mice without tissue damage or immunostimulation. OBJECTIVES AND METHODS: To investigate using flow cytometry, confocal microscopy, and quantitative imaging if chol-siRNAs silence gene expression in vaginal immune cells in mice. RESULTS: Although chol-siRNAs and lipoplexed-siRNAs silence gene expression in dendritic cells (DCs) in vitro, most internalized siRNAs concentrate within multivesicular bodies, where they are inaccessible to the cellular RNAi machinery. When applied intravaginally in vivo, chol-siRNAs penetrate the vaginal mucosa, including the lamina propria, and are efficiently internalized by intraepithelial (IE) and lamina propria (LP) DCs, and CD11b+ CD45+ cells, but not by T cells. Chol-siRNAs induce partial gene silencing in IE and LP DCs throughout the genital mucosa in vivo but are inactive in F4/80+ CD11b+ macrophages and T cells. CONCLUSION: As mucosal DCs play an essential role for mucosal viral entry and dissemination, chol-siRNAs could be harnessed to target various host factors that are critical for viral uptake, DC migration and trans-infection of virions to T cells, hence allowing the development of a preventive vaginal HIV microbicide. Furthermore, chol-siRNAs could help elucidate the pathways of HIV transmission and understand the immunologic function of DCs in the genital tract.

Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV.

Despite the development of vaccines, which protect healthy people from severe and life-threatening Covid-19, the immunological responses of people with secondary immunodeficiencies to these vaccines remain incompletely understood. Here, we investigated the humoral and cellular immune responses elicited by mRNA-based SARS-CoV-2 vaccines in a cohort of people living with HIV (PLWH) receiving anti-retroviral therapy. While antibody responses in PLWH increased progressively after each vaccination, they were significantly reduced compared to the HIV-negative control group. This was particularly noteworthy for the Delta and Omicron variants. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase, which was comparable in both groups. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4+ T cell numbers do not necessarily interfere with cellular immune responses. Our data demonstrate that despite the lower CD4+ T cell counts SARS-CoV-2 vaccination results in potent cellular immune responses in PLWH. However, the reduced humoral response also provides strong evidence to consider PLWH as vulnerable group and suggests subsequent vaccinations being required to enhance their protection against COVID-19.

Changes in the user profiles of HIV pre-exposure prophylaxis (PrEP) before and after PrEP reimbursement.

BACKGROUND: In Germany, oral HIV pre-exposure prophylaxis (PrEP) was licensed in 2016. Health insurances have been covering the costs since 09/2019. This study compares the sociodemographic profiles of PrEP users before and after PrEP re-imbursement. METHODS: Participants were recruited in a cross-sectoral sexual health centre in Germany. baseline data were compared for 139 vs 138 individuals starting PrEP from 10/2017-12/2018 (pre-reimbursement cohort) and 09/2019-3/2020; respectively. The pre-reimbursement cohort was further analysed with respect to sexual behaviour and incident sexually transmitted infections (STIs). RESULTS: There were no significant differences in the sociodemographic characteristics between the two cohorts. Almost all PrEP users were men-who-have-sex-with-men (MSM). Before reimbursement, fewer individuals used PrEP on a daily base, and more had used PrEP prior to enrolment. During follow-up (pre-reimbursement cohort), the number of sexual and condomless intercourse partners increased, so did the proportion engaging in Chemsex. Incidences of infections with C.trachomatis, N.gonorrhoeae, M.genitalium, and T.pallidum were 45.2; 36.8; 30.1; and 9.2, respectively, per 100 person-years. CONCLUSION: The goal to make PrEP available to a broader range of people with the covering of costs was only partially reached. Medically supervised use is important to detect and treat STIs.

S1 Guidelines for the Kaposi Sarcoma.

Kaposi's sarcoma (KS) is a rare, malignant, multilocular vascular disease originating from lymphatic endothelial cells that can primarily affect the skin and mucous membranes, but also the lymphatic system and internal organs such as the gastrointestinal tract, lungs or liver. Five epidemiological subtypes of KS with variable clinical course and prognosis are distinguished, with increased incidence in specific populations: (1) Classical KS, (2) Iatrogenic KS in immunosuppression, (3) Endemic (African) lymphadenopathic KS, (4) Epidemic, HIV-associated KS and KS associated with immune reconstitution inflammatory syndrome (IRIS), and (5) KS in men who have sex with men (MSM) without HIV infection. This interdisciplinary guideline summarizes current practice-relevant recommendations on diangostics and therapy of the different forms of KS. The recommendations mentioned in this short guideline are elaborated in more detail in the extended version of the guideline (online format of the JDDG).

S1-Leitlinie: Kaposi-Sarkom.

Das Kaposi-Sarkom (KS) ist eine seltene, maligne, von lymphatischen Endothelzellen ausgehende, multilokuläre Gefäßerkrankung, die vor allem Haut und Schleimhäute, aber auch das lymphatische System und innere Organe wie den Gastrointestinaltrakt, die Lunge oder die Leber befallen kann. Fünf epidemiologische Subtypen des KS mit variablem klinischem Verlauf und unterschiedlicher Prognose werden unterschieden, die in spezifischen Populationen vermehrt auftreten: (1) klassisches KS, (2) iatrogenes KS bei Immunsuppression, (3) endemisches (afrikanisches) lymphadenopathisches KS, (4) epidemisches, HIV-assoziiertes KS und mit einem Immunrekonstitutions-Inflammations-Syndrom (IRIS) assoziiertes KS und (5) KS bei Männern, die Sex mit Männern haben (MSM) ohne HIV-Infektion. Diese interdisziplinäre Leitlinie fasst aktuelle praxisrelevante Empfehlungen zu Diagnostik und Therapie der verschiedenen Formen des KS zusammen. Die in dieser Kurzleitlinie genannten Empfehlungen werden in der Langfassung der Leitlinie (Online-Version des JDDG) detaillierter ausgeführt.

HIV pre-exposure prophylaxis was associated with no impact on sexually transmitted infection prevalence in a high-prevalence population of predominantly men who have sex with men, Germany, 2018 to 2019.

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.

Online HIV/STI Risk Test (ORT): A prospective cross-sectional study among sexually active individuals in Germany.

BACKGROUND: Our goal was to develop and evaluate an anonymous self-administrable web-based test to determine risk for HIV/STI. METHODS: The Online HIV/STI Risk Test was developed and hosted since 12/2017. 11,529 participants completed the test and 10,668 were analyzed. The test included multiple choice questions about sociodemographic data, sexuality, sexual risk behavior, HIV/STI testing. Participant data was stratified by gender and sexuality and analyzed. RESULTS: 84.5 % were aged 18-39, 7.5 % < 18 and 8.1 % > 40. Males were 53.1 %, female 46.3 % and trans 0.6 %. 12.5 % were men who have sex with men (MSM). 59.1 % and 66.0 % of participants were vaccinated for hepatitis A and B respectively, but 75.1 % unvaccinated for HPV. Prior and repeated instances of HIV or other STI were higher among MSM. Yet, 61.4 % females, 70 % males and 55.4 % MSM had never tested for an STI. Although prevalence of > 3 sexual partners in the last twelve months was highest among MSM, condomless sex was greater among women. 34.5 % of males, 25.6 % of females, and 75 % of MSM engaged in anal sex respectively. CONCLUSIONS: The online HIV/STI Risk Test is a useful tool to acquire data on STI risk-behavior for strategizing STI prevention, testing, and vaccination, thus improving sexual health.

[Sexual behavior and prevention of sexually transmitted infections taking the SARS-CoV-2 pandemic into account. Data from a sexual healthcare and medicine center-WIR]. / Sexualverhalten und Prävention sexuell übertragbarer Infektionen unter Berücksichtigung der SARS-CoV-2-Pandemie. Daten aus einem Versorgungszentrum für sexuelle Gesundheit und Medizin ­ WIR.

BACKGROUND: Application-based data regarding sexual health and sexual behavior in various sexually active populations are scarce but at the same time relevant with regards to prevention and healthcare supply strategies. Given the structure of its attendees, the Walk In Ruhr (WIR) Center for Sexual Health and Medicine is able to obtain data from diverse living environments. OBJECTIVES: Based on the online HIV/STI risk test, questionnaires, and attendee data from the WIR, this study aims to deduce population-related findings with regards to age, gender, sexual orientation, and sexual and risk behavior as well as the respective needs for prevention. The influence of the SARS-CoV-19 pandemic on sexual behavior is examined by comparing various phases. METHODS: The analyzed data sources are the online HIV/STI risk test, the COWIR, and the PrEP study as well as the immunological outpatient clinic and the public health department at the WIR. RESULTS: Notwithstanding contact restrictions, sexually transmitted infections (STIs) have increased from 2019 to 2020. Apart from men having sex with men and females having sex with females, young people also have an increased risk of STIs based on sexual practices and the number of sexual contacts. A large number of bisexual and transsexual contacts was found. SARS-CoV­2 led to a decrease in sexual contacts; sexual practices continued. There was a growing proportion of STI tests and the treatment rate including partner treatment rose. DISCUSSION: Data from the WIR center show that young attendees with an active sexual life are being reached. The results from questionnaires and the online HIV/STI risk test are mirrored in increased positive STI test results. These results vary depending on sexual behavior and sexual preferences such that specific strategies for sexual education, prevention, testing, and therapy are required.

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

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.

[Sexual health and medicine at the WIR-Walk In Ruhr: presentation of the center and results of the evaluation]. / Sexuelle Gesundheit und Medizin im WIR ­ Walk In Ruhr: Vorstellung des Zentrums und Ergebnisse der Evaluation.

BACKGROUND: Holistic sexual healthcare factors in diversity of social habitat and aims to improvise client outreach for prevention, testing, counseling, and treatment of STIs. Towards this goal, the immunology outpatient clinic, the public health department of Bochum, the AIDS Service Organization Bochum e. v., and other community-driven NGOs mutually cooperate under the umbrella of WIR - Walk In Ruhr, Centre for Sexual Health and Medicine. OBJECTIVES: WIR is an innovative concept for multi-professional in-house ambulatory healthcare with cross-sectoral and cross-legal reach. It has successfully improved accessibility, testing and treatment rates, and HIV/STI self-assessment. We present the results achieved at WIR. METHODS: A mixed-method design of qualitative and quantitative surveys. RESULTS: The WIR reaches more women (27.7%) and heterosexuals (56.4%) than other counseling/test centers. The rate of positive test results at the WIR increased from 9.3% in 2017 to 12.6% in 2018 and progress from prevention to medical care is a significant aspect of WIR. The Federal Ministry of Health has externally evaluated WIR for over three years. DISCUSSION: The integrative care model of WIR allows for early outreach and treatment of individuals with HIV/ST infections. Health advisors remain an important instrument facilitating outreach and psychosocial/psychotherapeutic counseling is administered frequently. Such a multi-layered approach in prevention, testing, and consultation, leads to improvement in both medical outcomes and the self-responsible attitude of patients towards their sexual health. Hence, expansion of integrative care models like WIR on a wider scale could arguably contribute to better health service and sexual health.