HIV-Präexpositionsprophylaxe-Versorgung in intersektoraler Zusammenarbeit

$\it Hintergrund$ Zur HIV("human immunodeficiency virus")-Präexpositionsprophylaxe (PrEP) wird am WIR – Walk In Ruhr – Zentrum für Sexuelle Gesundheit und Medizin ein innovatives Modellprojekt zur intersektoralen PrEP-Versorgung durchgeführt. $\it Forschungsziele$ Die vorliegende Studie beschreibt, wer mit der PrEP versorgt wurde und wie sich im Verlauf der PrEP-Einnahme das sexuelle Risikoverhalten änderte sowie welche sexuell übertragbaren Infektionen (STI) und unerwünschte Arzneimittelwirkungen auftraten. $\it Methoden$ In die Studie wurden bisher $\it N$ = 139 Probanden eingeschlossen, die zwischen 10/2017 und 12/2018 mit einer PrEP begonnen haben. Alle PrEP-Nutzer erhielten Fragebögen, zudem wurden Nebenwirkungen, HIV und andere STI mittels klinischer Laborwerte über einen Zeitraum von 13 Monaten erfasst. $\it Ergebnisse$ Die PrEP-Nutzer hatten ein durchschnittliches Alter von 38 Jahren, waren zu 98,6 % Männer, die Sex mit Männern (MSM) hatten, und zeichneten sich durch einen hohen Bildungsstatus und geringe Arbeitslosigkeit aus. Die durchschnittliche Partneranzahl pro Proband innerhalb der letzten 6 Monate stieg im Verlauf signifikant an, während die Kondomnutzung signifikant zurückging. Innerhalb der ersten 4 Monate nach PrEP-Beginn traten 44 STI bei 34 Patienten auf. Es wurde keine HIV-Infektion festgestellt. In den ersten 4 Wochen nach PrEP-Beginn zeigten sich bei 38,8 % der Probanden unerwünschte Arzneimittelwirkungen, hauptsächlich Symptome des Magen-Darm-Trakts. $\it Schlussfolgerung$ Die PrEP-Nutzer hatten einen guten Bildungsstatus und einen festen Arbeitsplatz bzw. eine Ausbildungsstelle. Das sexuelle Risikoverhalten nahm im Verlauf zu, verbunden mit einem gehäuften Auftreten von STI. Unerwünschte Arzneimittelwirkungen zeigten sich insbesondere zu Anfang der PrEP-Einnahme.$\it Background$ HIV pre-exposure prophylaxis (PrEP), a further opportunity to prevent HIV, is available at the WIR—Walk In Ruhr, Centre for Sexual Health and Medicine, as part of an innovative model project for intersectoral PrEP care. $\textit {Research objectives}$ The present study describes the collective of persons provided with PrEP and how PrEP use influences sexual risk behaviour, the incidence of sexually transmitted diseases (STD) and adverse drug reactions. $\it Methods$ A total of 139 men who started PrEP between 10/2017 and 12/2018 have been included in the study. During a period of 13 months of PrEP treatment, all PrEP users received questionnaires; side effects, HIV and other STI were also monitored via clinical laboratory examinations. $\it Results$ The participants’ average age was 38 years and 98.6% of them were men who had sex with men (MSM). Most of them had a high educational background; the unemployment rate was low. The average number of sexual partners within the last 6 months increased significantly, while the use of condoms decreased. In all, 44 STI were found in 34 participants within the first 4 months. No one was infected with HIV. Within the first 4 weeks of PrEP, 38.8% of the participants suffered from side effects, mainly gastrointestinal symptoms. $\it Conclusion$ Most of the participants were working in a job or a vocational training. The sexual risk behaviour increased in the course of using PrEP resulting in a high incidence of STD. Side effects appeared most frequently in the first few weeks after starting PrEP

Sexuelle Gesundheit und Medizin im WIR – Walk In Ruhr

$\bf Hintergrund:$ Ein ganzheitliches Konzept sexueller Gesundheit und Medizin berücksichtigt die Diversität von Lebenswelten, um Klient*innen für Prävention, Testung, Beratung und Behandlung sexuell übertragbarer Infektionen (STI) zu gewinnen. Mit diesem Verständnis arbeiten die Immunologische Ambulanz, das Gesundheitsamt, die Aidshilfe sowie weitere Selbsthilfeorganisationen im WIR – Walk In Ruhr, Zentrum für Sexuelle Gesundheit und Medizin, in Bochum zusammen. $\textbf {Ziel der Arbeit:}$ Am Beispiel des WIR, das mit seinem innovativen Konzept eines Versorgungszentrums multiprofessionell innerhalb eines Settings sektor- und rechtsformübergreifend arbeitet, wird gezeigt, dass Erreichbarkeit, Test- und Behandlungsquote und HIV/STI-Risiko-Selbsteinschätzung sich verbessern. Das WIR wurde zudem im Auftrag des Bundesministeriums für Gesundheit über 3 Jahre extern evaluiert auch diese Ergebnisse werden dargestellt. $\bf Methode:$ Das Konzept des WIR und die im WIR durchgeführten Studien werden deskriptiv dargestellt. Bei der externen Evaluation wurde ein Mixed-Method-Design aus quantitativen und qualitativen Erhebungen angewandt. $\bf Ergebnis:$ Durch die Kooperation werden häufiger Frauen (27,7 %) und Heterosexuelle (56,4 %) als in der Ambulanz allein erreicht. Die Rate positiver Testergebnisse im WIR stieg von 2017 bis 2018 von 9,3 % auf 12,6 %. $\bf Diskussion:$ Durch das integrative Versorgungskonzept des WIR gelingt es, Menschen mit HIV/STI früh zu erreichen und zu behandeln. Der Übergang von Prävention zu medizinischer Versorgung ist im WIR von zentraler Bedeutung. Gesundheitsberater sind ein wichtiges Instrument für die aufsuchende Arbeit. Psychosoziale sowie psychotherapeutische Beratung werden in hohem Maße genutzt. Durch die vielschichtigen Angebote von Prävention, Test, Beratung werden bessere medizinische Ergebnisse erreicht sowie die Eigenverantwortung für sexuelle Gesundheit gesteigert. Die Übertragung des Konzeptes in die Fläche kann einen Beitrag zur besseren Versorgung zu sexueller Gesundheit leisten.$\bf Background:$ 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. $\bf Objectives:$ 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. $\bf Methods:$ A mixed-method design of qualitative and quantitative surveys. $\bf Results:$ 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. $\bf Discussion:$ 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

Functional energetics of CD4+CD4^{+}-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders

$\textit {Background:}$ Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system- (CNS-) infection that typically occurs in a subset of immunocompromised individuals. An increasing incidence of PML has recently been reported in patients receiving monoclonal antibody (mAb) therapy for the treatment of autoimmune diseases, particularly those treated with natalizumab, efalizumab and rituximab. Intracellular $CD4^{+}$-ATP-concentration (iATP) functionally reflects cellular immunocompetence and inversely correlates with risk of infections during immunosuppressive therapy. We investigated whether iATP may assist in individualized risk stratification for opportunistic infections during mAb-treatment. $\textit {Methodology/Principal Findings:}$ iATP in PHA-stimulated, immunoselected $CD4^{+}$-cells was analyzed using an FDA-approved assay. iATP of mAb-associated PML (natalizumab (n = 8), rituximab (n = 2), efalizumab (n = 1)), or other cases of opportunistic CNS-infections (HIV-associated PML (n = 2), spontaneous PML, PML in a psoriasis patient under fumaric acids, natalizumab-associated herpes simplex encephalitis (n = 1 each)) was reduced by 59% (194.5$\pm$29 ng/ml, mean$\pm$SEM) in comparison to healthy controls (HC, 479.9$\pm$19.8 ng/ml, p<0.0001). iATP in 14 of these 16 patients was at or below $3^{rd}$ percentile of healthy controls, similar to HIV-patients (n = 18). In contrast, $CD4^{+}$-cell numbers were reduced in only 7 of 15 patients, for whom cell counts were available. iATP correlated with mitochondrial transmembrane potential ($\Delta\Psi_{m}$) (iATP/$\Delta\Psi_{m}$−correlation:tau = 0.49, p = 0.03). Whereas mean iATP of cross-sectionally analysed natalizumab-treated patients was unaltered (448.7$\pm$12 ng/ml, n = 150), iATP was moderately decreased (316.2$\pm$26.1 ng/ml, p = 0.04) in patients (n = 7) who had been treated already during the pivotal phase III trials and had received natalizumab for more than 6 years. 2/92 (2%) patients with less than 24 months natalizumab treatment revealed very low iATP at or below the $3^{rd}$ percentile of HC, whereas 10/58 (17%) of the patients treated for more than 24 months had such low iATP-concentrations. $\textit {Conclusion:}$ Our results suggest that bioenergetic parameters such as iATP may assist in risk stratification under mAb-immunotherapy of autoimmune disorders

Sexual behaviour, STI knowledge and Chlamydia trachomatis\textit {Chlamydia trachomatis} (CT) and Neisseria gonorrhoeae\textit {Neisseria gonorrhoeae} (NG) prevalence in an asymptomatic cohort in Ruhr-area, Germany

$\textbf {Background and objectives}$ STIs present a significant threat to individual and public health, disproportionately affecting youth. The study aimed to evaluate (a) the prevalence of asymptomatic $\textit {Chlamydia trachomatis}$ (CT) and $\textit {Neisseria gonorrhoeae}$ (NG) infections among youth using a rapid assay platform, (b) the participants' sexual behaviour and STI knowledge, (c) the utility of the rapid assay in reducing diagnosis-to-treatment time. $\bf Methods$ In this study, 272 subjects (14–31 years) were included between 12/2016 and 7/2018. A questionnaire was used to collect sociodemographic data, sexual behaviour and STI knowledge. Prevalence of CT and NG infections were tested from oral, vaginal and anal swabs for women and oral, anal swabs and urine for men, using the Cepheid Xpert® CT/NG assay. Time intervals between (i) test to the time the patient were informed of the result (turn around time – TAT) and (ii) test to therapy initiation was documented. $\bf Results$ Of the 272 subjects (48.9% female, 48.9% male, undisclosed 2.2%), 56.6 % reported university education. 46.6% were men who have sex with men (MSM), and 47.4% of women and 63.1% of men had anal intercourse. 59.9% had previously been tested for HIV, while only 39.7% had for CT, 20.6% for NG. Among these asymptomatic youth 7.7% were positive for CT and 5.5% for NG. The localization of CT were 3.7% genital, 5.5% anal and 2.2% oral, while the corresponding localization of NG were 0.4%, 2.9%, 4.4% respectively. 91.8% of the participants were informed of a positive result within 24 h with a median TAT of 03:09 h. 73.3% initiated therapy within 24 h, with a median time from testing to therapy initiation being 06:50 h. $\bf Conclusion$ Asypmtomatic CT and NG infections are common and often not tested in persons at risk. The Cepheid Xpert® CT/NG assay is an effective strategy as it reduces STI diagnosis-to-treatment time to less than a day

HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic

$\bf Aims:$ Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. $\bf Methods:$ The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). $\bf Results:$ During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the $2^{nd}$ quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in $1^{st}$ quarter of 2020, to 7 partners in $4^{th}$ quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. \(\bf Conclusion:\9 The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis

Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18

G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology

Characterization of the olfactory receptors expressed in human spermatozoa

The detection of external cues is fundamental for human spermatozoa to locate the oocyte in the female reproductive tract. This task requires a specific chemoreceptor repertoire that is expressed on the surface of human spermatozoa, which is not fully identified to date. Olfactory receptors (ORs) are candidate molecules and have been attributed to be involved in sperm chemotaxis and chemokinesis, indicating an important role in mammalian spermatozoa. An increasing importance has been suggested for spermatozoal RNA, which led us to investigate the expression of all 387 OR genes. This study provides the first comprehensive analysis of OR transcripts in human spermatozoa of several individuals by RNA-Seq. We detected 91 different transcripts in the spermatozoa samples that could be aligned to annotated OR genes. Using stranded mRNA-Seq, we detected a class of these putative OR transcripts in an antisense orientation, indicating a different function, rather than coding for a functional OR protein. Nevertheless, we were able to detect OR proteins in various compartments of human spermatozoa, indicating distinct functions in human sperm. A panel of various OR ligands induced Ca$^{2+}$ signals in human spermatozoa, which could be inhibited by mibefradil. This study indicates that a variety of ORs are expressed at the mRNA and protein level in human spermatozoa

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