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

Antibiotic Resistance and Genotypes of Mycoplasma genitalium during a Resistance-Guided Treatment Regime in a German University Hospital

The treatment of infections from the sexually transmitted pathogen Mycoplasma genitalium is hampered by the rapidly increasing resistance to the recommended first- (macrolides) and second-line antibiotics (quinolones). Thus, resistance-guided therapy (RGT) is key for its successful eradication but the efficiency of this approach can be influenced by re-infections and treatment failures. The typing of strains is helpful to distinguish between ongoing colonization, re-infection or the development of resistance. In the present study, mgpB and MG_309 types as well as mutations associated with macrolide, quinolone and tetracycline resistance of strains in M. genitalium-positive samples accumulated in the years 2019 and 2020 at a university hospital were analyzed. Fifty-eight positive first and sixteen positive follow-up samples from patients (96.6% male, 84.5% men who have sex with men, 74.1% HIV-positive) were included. Twenty-three mgpB types (seven new types), nine MG_309 types and thirty-four mgpB/MG_309 types were identified. The prevalence of mutations associated with macrolide, quinolone and tetracycline resistance was 56.9%, 10.3% and 6.8%, respectively. Despite the fact that many asymptomatic patients were not treated and tests of cure were impossible in different cases, the preliminary rate of successful eradication (93.3%) in this study is promising for the continuation of the RGT strategy

Prevalence and antibiotic resistance of rectal Mollicutes in HIV-infected men who have sex with men at the University Hospital of Dresden, Germany

Background!#!Rectal sexually transmitted infections (STI) are common in men having sex with men (MSM). Mycoplasma genitalium is increasingly being reported in this localization, but due to frequent lack of symptoms at this site, clinical significance is still unclear. Rectal prevalence of Mycoplasma hominis and Ureaplasma species is not well studied so far. We aimed to investigate the prevalence and antibiotic sensitivity of rectal Mollicutes in our HIV-cohort.!##!Methods!#!In 227 MSM presenting for annual STI-screening, 317 anorectal swabs were collected from January 2017 to December 2018. PCR was performed for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, M. genitalium and also culture for M. hominis and Ureaplasma spec.!##!Results!#!Prevalence for M. genitalium, M. hominis, Ureaplasma spec., C. trachomatis and N. gonorrhoeae was 8.2%, 7.3%, 12.0%, 5.1% and 1.9%, respectively. Patients were asymptomatic with few exceptions. Seroprevalence of syphilis in 227 MSM was 41.9%. In 20 strains of M. genitalium, resistance-associated mutations to macrolides and quinolones were found in 60% and 30%, respectively; in five strains (25%) to both. M. hominis and Ureaplasma spec. frequently occurred combined, mostly in significant quantity consistent with infection. M. hominis and Ureaplasma spec. regularly showed sensitivity to tetracycline.!##!Conclusion!#!At screening, rectal colonization with Mollicutes was common in our patients, but rarely caused symptoms. Due to rising antibiotic resistance of M. genitalium against quinolones, therapeutic options are increasingly limited. Treatment should be guided by antibiotic resistance testing including quinolones. In persisting anorectal symptoms, M. hominis and Ureaplasma spec. should also be taken into account

Successful immunotherapy and irradiation in a HIV-positive patient with metastatic Merkel cell carcinoma

This case report presents a HIV-positive 60-year old male with Merkel cell carcinoma of his right forearm and pulmonary sarcoidosis, who, after excisions and irradiations of the primary tumour site and subsequent lymph node metastases developed distant metastases. He received radiotherapy to symptomatic mediastinal lymph node metastases followed by Doxorubicin and, after two cycles, by the PD-1 inhibitor Pembrolizumab due to mixed response. Re-staging showed a para-mediastinal, radiotherapy-induced pneumonitis, which was treated by prednisolone due to clinical symptoms. In September 2017, the patient developed a solitary lymph node metastasis next to the right atrium, for which he received stereotactic radiotherapy. The systemic treatment with Pembrolizumab was replaced by the PD-L1 inhibitor Avelumab and is being continued since. The patient has been in complete remission for one year now and the HIV-infection is well-controlled. Keywords: Merkel cell carcinoma, Avelumab, Immunotherapy, Pembrolizumab, Immune checkpoint inhibition, Radiotherapy, HIV, Sarcoidosi

STI in times of PrEP: high prevalence of chlamydia, gonorrhea, and mycoplasma at different anatomic sites in men who have sex with men in Germany

Background Men who have sex with men (MSM) are disproportionally affected by sexually transmitted infections (STI). STI are often extragenital and asymptomatic. Both can delay diagnosis and treatment. Approval of HIV pre-exposure prophylaxis (PrEP) might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. Methods We conducted a nationwide, cross-sectional study between February and July 2018. Thirteen MSM-friendly STI-practices screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples. APTIMA™ STI-assays (Hologic™ Inc., San Diego, USA) were used for diagnostics, and samples were not pooled. We collected information on socio-demographics, HIV-status, clinical symptoms, sexual behaviour within the last 6 months, and PrEP use. We combined HIV status and PrEP use for defining risk groups, and used directed acyclic graphs and multivariable logistic regression to identify risk factors for STI. Results Two thousand three hundred three MSM were included: 50.5% HIV+, median age 39 [18–79] years. Median number of male sex partners within the last 6 months was five. Sex without condom was reported by 73.6%, use of party drugs by 44.6%. 80.3% had a STI history, 32.2% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 30.1, 25.0% in HIV−/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV−/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.8%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Being HIV+ (OR 1.7, 95%-CI 1.3–2.2), using PrEP (OR 2.0, 95%-CI 1.5–2.7), having > 5 sex partners (OR:1.65; 95%-CI:1.32–2.01.9), having condomless sex (OR:2.11.9; 95%-CI:1.65–2.86), and using party drugs (OR:1.65; 95%-CI:1.32–2.0) were independent risk factors for being tested positive for at least one STI. Conclusions We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. As a relevant proportion of PrEP users will not use a condom, counselling and comprehensive STI screening is essential and should be low threshold and preferably free of cost. Counselling of PrEP users should also address use of party drugs.Peer Reviewe

Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study

Background. Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH). Methods. DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA = 24 weeks (1 accepted blip = 50 copies/ml, at W48 were 1.6% (n = 2) in the 2DR and 3.1% (n = 4) in the 3DR group. Development of treatment-emergent resistance was not observed. Conclusions. Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV