Limited information is available regarding the efficacy of antiretrovirals in people with HIV-1 and high or very high Body Mass Index (BMI). This is especially the case for the alafenamide salt of tenofovir as clinical trials have only enrolled patients with BMI ≤30 kg/m 2 . Lower concentrations of some antiretrovirals are expected in patients with BMI >30 kg/m 2 due to potential changes in clearance and distribution of medication. This report describes an individual taking tenofovir alafenamide, emtricitabine and efavirenz in whom HIV-1 viral load was consistently undetectable (<50 copies/ml) over a 2.5 year period. During this period the patient’s BMI ranged between 59.8 and 68.1 kg/m 2 . Further data is required to support the efficacy of antiretrovirals in individuals with high and very high BMI.

Introduction In response to the national shortage of procaine penicillin for first-line neurosyphilis treatment we designed a treatment pathway using intravenous (IV) Ceftriaxone 2 grams for 14 days delivered via our local outpatient parenteral antibiotic treatment (OPAT) services from November 2021. We present clinical outcomes from our cohort. Methods A retrospective case notes analysis of patients treated with Ceftriaxone IV for neurosyphilis, ocular and otosyphilis between November 2021 – March 2023 was performed. Anonymised clinical and epidemiological data was collected from electronic patient records and analysed using Excel spreadsheets. Results 16 patients were identified. All cisgender and 14 (87.5%) were male, median age 49 years (IQR 23–68). Ethnicity was documented in 9/16– majority of whom were white British (77.7%). 11 were MSM, 1 bisexual, 3 heterosexual. 1 declined to disclose their sexuality. 2 (12.5%) were HIV positive (CD4 390, 480 cells/mm3). 2 (12.5%) were on HIV PrEP. 3 (18.7%) patients had a concurrent STI. 11 (68.7%) reported visual symptoms; 10 with ocular changes consistent with ocular syphilis. 7 (43.7%) reported hearing loss, tinnitus or vertigo: 4 had confirmed sensorineural high frequency hearing loss. 3 (18.7%) had concurrent ocular and otosyphilis. Median RPR at diagnosis was 1:32. 100% completed treatment. Serological outcome data is currently available for 6 patients (37.5%) at 3 months and 6 months respectively post-treatment. 5/6 (83.3%) patients achieved a serological response of >2 titre RPR reduction in 3 months. 12 (75%) reported complete or partial symptom resolution so far. Discussion Our work adds to emerging data demonstrating Ceftriaxone as a successful treatment option for neurosyphilis. Using an IV line for the whole treatment course simplified the pathway and achieved excellent completion rates. Future work is planned to assess patient satisfaction and service impact.

BackgroundFollow up of treated syphilis (STS) with a non-treponemal test (NTT) is recommended to identify treatment relapse and re-infection. National guideline suggests a NTT at three, six and twelve months, or until serofast. This study aimed to assess application of current advice.MethodsWe conducted a retrospective review of all positive STS serology results for a busy London sexual health clinic between March and July 2021. A total of 106 patients were identified using STS codes and recall data. Patient’s electronic records (Lilie v10, CERNER and Sexual Health London portal) were reviewed for clinical and epidemiological data up to twelve months post STS treatment. Data was analysed using MS Excel.ResultsMost patients were male (96%) and living with HIV (54%). Early STS affected 85%, and 86% received Benzathine Penicillin. Whilst 82% had a NTT pre-treatment, 16% did not have any documented subsequently. Moreover, no NTT was recorded at six months for 75%. Lastly, only 34%, 25%, and 29% of all patients had a test recorded at three, six, and twelve months respectively.ConclusionsNTT obtained pre -treatment rate was high, but did not reach the standard 97% of confirmed STS. Similarly, our cohort did not reach the minimum of 65% documented NTT six months post treatment. These data are consistent with previous studies showing suboptimal STS follow up. The rates of timely NTT were low despite the proportion of patients living with HIV, who are likely to attend clinic twice yearly. Recommendations should include booking 3x NTT appointments at treatment day; synchronisation of HIV bloods with STS follow up and electronic reminders. Patient advice should emphasise the importance of follow up to identify STS treatment failure and reinfection.

BACKGROUND:Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum subspecies pallidum. Since 2012, syphilis rates have risen dramatically in many high-income countries, including England. Although this increase in syphilis prevalence is known to be associated with high-risk sexual activity in gay, bisexual, and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women. The transmission dynamics within and between sexual networks of GBMSM and heterosexual people are not well understood. We aimed to investigate if whole genome sequencing could be used to supplement or enhance epidemiological insights around syphilis transmission. METHODS:We linked national patient demographic, geospatial, and behavioural metadata to whole T pallidum genome sequences previously generated from patient samples collected from across England between Jan 1, 2012, and Oct 31, 2018, and performed detailed phylogenomic analyses. FINDINGS:Of 497 English samples submitted for sequencing, we recovered 240 genomes (198 from the UK Health Security Agency reference laboratory and 42 from other laboratories). Three duplicate samples (same patient and collection date) were included in the main phylogenies, but removed from further analyses of English populations, leaving 237 genomes. 220 (92·8%) of 237 samples were from men, nine (3·8%) were from women, and eight (3·4%) were of unknown gender. Samples were mostly from London (n=118 [49·8%]), followed by southeast England (n=29 [12·2%]), northeast England (n=24 [10·1%]), and southwest England (n=15 [6·3%]). 180 (76·0%) of 237 genomes came from GBMSM, compared with 25 (10·5%) from those identifying as men who have sex with women, 15 (6·3%) from men with unrecorded sexual orientation, nine (3·8%) from those identifying as women who have sex with men, and eight (3·4%) from people of unknown gender and sexual orientation. Phylogenomic analysis and clustering revealed two dominant T pallidum sublineages in England. Sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in GBMSM older than 34 years and was absent from samples sequenced from the north of England. These different spatiotemporal trends, linked to demography or behaviour in the dominant sublineages, suggest they represent different sexual networks. By focusing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission in GBMSM. INTERPRETATION:These findings show that, despite extremely close genetic relationships between T pallidum genomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up. This could be of value for deconvoluting putative outbreaks and for informing public health interventions. FUNDING:Wellcome funding to the Sanger Institute, UK Research and Innovation, National Institute for Health and Care Research, European and Developing Countries Clinical Trials Partnership, and UK Health Security Agency.

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive and often fatal neuroendocrine skin cancer. The incidence of MCC has significantly increased in the last decades. Factors that have been associated with the development of MCC include infection with Merkel Cell polyomavirus (MCPyV), ultraviolet exposure, hematologic malignancies and immunosuppression.We present three cases of patients living with HIV who were diagnosed with MCC. HIV cases associated with MCC have been rarely reported and to our knowledge, not yet before in the UK.

Background Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum subspecies pallidum , with approximately 6.3 million annual cases globally. Over the last decade, syphilis rates have risen dramatically in many high-income countries, including in England, which has seen a greater than 150% increase. Although this increase is known to be associated with high risk sexual activity in gay, bisexual and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women, and congenital syphilis cases are now seen annually. The transmission dynamics within and between sexual networks of GBMSM and heterosexuals are not well understood. Methods To determine if whole genome sequencing could be used to identify discrete patterns of transmission, we linked national patient demographic, geospatial and behavioural metadata to whole T. pallidum genome sequences previously generated from 237 patient samples collected from across England between 2012 and 2018. Findings Phylogenomic analysis and clustering revealed two of the eight T. pallidum sublineages detected in England dominated. These dominant sublineages exhibited different spatiotemporal trends linked to demography or behaviour, suggesting they represent different sexual networks: sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in older GBMSM and was absent from samples sequenced from the North of England. By focussing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission amongst GBMSM. Interpretation These findings demonstrate that despite extremely close genetic relationships between T. pallidum genomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up, and therefore has a role to play in informing public health interventions. Funding Wellcome funding to the Sanger Institute (#206194 and 108413/A/15/D), UKRI and NIHR (COV0335; MR/V027956/1, NIHR200125), the EDCTP (RIA2018D-249), and UKHSA. Evidence before this study Detailed phylogenomic analyses investigating the epidemiology and transmission dynamics of Treponema pallidum are challenging due to low bacterial loads in clinical specimens, and difficulty in culturing the bacteria. We searched PubMed until August 9th 2022 using the search terms “Syphilis” or “ Treponema pallidum ” and “genomic” or “genome(s)” or “sequencing”, finding 23 studies describing whole genome sequencing of T. pallidum subspecies pallidum , of which two used whole genome phylogenies to investigate sexual network epidemiology, with one large study of sexual networks conducted primarily in Victoria, Australia which characterised two major circulating sublineages in that setting, as well as putative sexual transmission networks with distinct sexual behavioural characteristics and potential bridging between networks. Added value of this study In this study, we linked national surveillance data to T. pallidum genomes, and characterised the transmission dynamics of syphilis using samples from across a whole country, in a European setting (England). Integration of national-level sociodemographic, spatiotemporal and genomic data allowed the delineation of putative sexual networks at both the national and region levels, and revealed patterns not previously detected using epidemiological or genomic data alone. Implications of all the available evidence Our findings are consistent with findings in Australia that demonstrate genomics can identify putative sociodemographic transmission clusters. However, in that study genomic clusters included samples separated by multiple single nucleotide polymorphisms, which could represent several years of evolution. Our study explored the value of linking identical genomes, and highlights that despite technical constraints, whole genome sequencing can be used to enable outbreak exclusion and identify putative local transmission clusters for epidemiological follow-up. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement MAB and NRT were supported by Wellcome funding to the Sanger Institute (#206194 and 108413/A/15/D). MM was funded by the UKRI and NIHR (COV0335; MR/V027956/1, NIHR200125) and the EDCTP (RIA2018D-249). Staff time for LT, MJC, RP, HC, KS, HF, patient metadata retrieval and analyses were funded internally by UKHSA. This research was funded in whole, or in part, by the Wellcome Trust (#206194 and 108413/A/15/D). For the purpose of open access, the authors have applied a CC-BY public copyright licence to any author-accepted manuscript version arising from this submission. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for all clinical samples was granted by the London School of Hygiene and Tropical Medicine Observational Research Ethics Committee (REF#16014) and the National Health Service (UK) Health Research Authority and Health and Care Research Wales (UK; 19/HRA/0112). UKHSA has permission to process confidential patient data under Regulation 3 (Control of Patient Information) of the Health Service Regulations 2002. Information governance advice and ethics approval for this study were granted by the PHE (now UKHSA) Research Ethics and Governance Group. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Sequencing reads for all genomes used in this study have been previously published and described, and are available at the European Nucleotide Archive () in BioProjects PRJEB28546, PRJEB33181 and PRJNA701499. All accessions, corresponding sample identifiers and related metadata are available in Supplementary Data 1. Patient metadata for the UK genomes is available in pseudonymised form in Supplementary Data 2. UK shape files for Public Health (UKHSA) region boundaries were downloaded from the UK Office for National Statistics, available at . All sample metadata and intermediate analysis files are available at and [https://github.com/matbeale/Syphilis\_Genomic\_Epi\_England\_2022-23][1]. [https://github.com/matbeale/Syphilis\_Genomic\_Epi\_England\_2022-23][1] [1]: https://github.com/matbeale/Syphilis_Genomic_Epi_England_2022-23

Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.

Objectives Understanding the public health impact of lymphogranuloma venereum (LGV) in Europe is hampered by inadequate diagnostics and surveillance systems in many European countries. We developed and piloted LGV surveillance in three European countries without existing systems and performed a preliminary investigation of LGV epidemiology, where little evidence currently exists. Methods We recruited STI or dermatovenereology clinics and associated laboratories serving men who have sex with men (MSM) in Austria, Croatia and Slovenia, using the UK for comparison. We undertook centralised LGV testing of Chlamydia trachomatis (CT)-positive rectal swabs collected between October 2016 and May 2017 from MSM attending these clinics. Stored specimens from Austria (2015-2016) and Croatia (2014) were also tested. Clinical and sociodemographic data were collected using a standardised proforma. The ompA gene of LGV-positive specimens was sequenced. Results In total, 500 specimens from CT-positive MSM were tested, and LGV positivity was 25.6% (128/500; 95%CI 22.0% to 29.6%) overall, and 47.6% (79/166; 40.1% to 55.2%) in Austria, 20.0% (3/15; 7.1% to 45.2%) in Croatia, 16.7% (1/6; 3.0% to 56.4%) in Slovenia and 14.4% (45/313; 10.9% to 18.7 %) in the UK. Proformas were completed for cases in Croatia, Slovenia and in the UK; proformas could not be completed for Austrian cases, but limited data were available from line listings. Where recorded, 83.9% (78/93) of LGV-CT cases were HIV-positive compared with 65.4% (149/228) of non-LG V-CT cases; MSM with LGV-C T were more likely to have proctitis (Austria, 91.8% vs 40.5%, p<0.001; Croatia, 100% vs 25%, p=0.04; UK, 52.4% vs 11.7%, p<0.001) than those with non-LG V-CT. Six different ompA sequences were identified, including three new variants; the L2 ompA sequence predominated (58.6%, 51/87). Conclusions LGV is substantially underdiagnosed in MSM across Europe. Unified efforts are needed to overcome barriers to testing, establish effective surveillance, and optimise diagnosis, treatment and prevention.

Syphilis rates have been increasing in men who have sex with men (MSM) in London. To describe risk behaviour and refine public health interventions, we conducted prospective enhanced surveillance of new syphilis cases in MSM attending selected London sexual health clinics (SHCs) between October 2016 and January 2017. Sexual health advisors (SHAs) completed 107 questionnaires. Eighteen per cent of respondents reported always using condoms, with lower use in HIV-positive (8%, 4/53) than HIV-negative men (33%, 14/52). Almost half of respondents reported condomless sero-discordant sex (46%, 33/72). The most frequent means of meeting new partners reported were venues (80%, 76/95), particularly bars or clubs (34%, 32/95), and apps or websites (79%, 75/95). Nearly a third of respondents reported engaging in group sex (32%, 30/95). Almost half reported drug use during sex (47%, 46/98), with HIV-positive men more likely to report use of the three main ‘chemsex’ drugs. The majority of respondents preferred health promotion information from SHAs (63%, 58/92) compared to other sources such as Google/Wikipedia and apps. Prevention activity should continue to focus on condomless sex, serosorting, multiple and overlapping partners, and chemsex. SHCs, particularly those serving HIV-positive men, are important sources for sexual health promotion advice.

British Journal of Hospital MedicineVol. 79, No. 4 EditorialDon't forget about syphilis: the great pretenderNina Vora, Patrick FrenchNina VoraSearch for more papers by this author, Patrick FrenchSearch for more papers by this authorNina Vora; Patrick FrenchPublished Online:5 Apr 2018https://doi.org/10.12968/hmed.2018.79.4.188AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Chen MY, Klausner JD, Fairley CK, Guy R, Wilson D, Donovan B (2015) Syphilis: a fresh look at an old foe. Sex Health 12(2): 93–95. https://doi.org/https://doi.org/10.1071/SH15025 Crossref, Medline, Google ScholarHawkes S, Matin N, Broutet N, Low N (2011) Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis. Lancet Infect Dis 11(9): 684–691. https://doi.org/https://doi.org/10.1016/S1473-3099(11)70104-9 Crossref, Medline, Google ScholarKenyon CR, Osbak K, Tsoumanis A (2016) The global epidemiology of syphilis in the past century – a systematic review based on antenatal syphilis prevalence. PLoS Negl Trop Dis 10(5): e0004711. https://doi.org/https://doi.org/10.1371/journal.pntd.0004711 Crossref, Medline, Google ScholarKingston M, French P, Higgins S, et al.; Members of the Syphilis guidelines revision group 2015 (2016) UK national guidelines on the management of syphilis 2015. Int J STD AIDS 27(6): 421–446. https://doi.org/https://doi.org/10.1177/0956462415624059 Crossref, Medline, Google ScholarMindel A, Tovey SJ, Timmins DJ, Williams P (1989) Primary and secondary syphilis, 20 years experience. 2. Clinical features. Genitourin Med 65(1): 1–3. Medline, Google ScholarPublic Health England (2016) Syphilis epidemiology in London. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/547072/london_syphilis_report.pdf (accessed 3 January 2018) Google ScholarPublic Health England (2017) ‘Antenatal screen negative’ Congenital Syphilis. www.rcpch.ac.uk/system/files/protected/news/PHE-Congenital-syphilis-alert-2017-02.pdf (accessed 11 January 2018) Google ScholarTipple C (2015) Impact of HIV-1 infection on the clinical presentation of syphilis in men who have sex with men. Sex Health 12(2): 110–118. https://doi.org/https://doi.org/10.1071/SH14157 Crossref, Medline, Google Scholar FiguresReferencesRelatedDetailsCited byThe great imitator: neurosyphilis presenting as subacute confusionNatasha G, Elinor Moore, Nyarie Sithole30 June 2021 | British Journal of Hospital Medicine, Vol. 82, No. 6 2 April 2018Volume 79Issue 4ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 5 April 2018 Published in print 2 April 2018 Information© MA Healthcare LimitedPDF download

Within a century, congenital syphilis has been reduced from a major cause of morbidity and mortality to a condition rarely seen in the UK. Here, newly-derived literature and information searches were used to create a contemporary overview of the epidemic, including its epidemiology. Although constrained by high-quality healthcare services and with an incidence below the World Health Organization elimination threshold, congenital syphilis still has the potential to cause major consequences for the health and life chances of affected infants. If the complex challenges presented by this preventable disease are to be resolved, intervention strategies need to be optimised, rigorously assessed and extended across Europe.

Syphilis is a sexually transmitted infection caused by Treponema pallidum subspecies pallidum and may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. Here we use direct sequencing of T. pallidum combined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves in Treponema subspecies and provide a warning on broader issues of antimicrobial resistance.

Background Lymphogranuloma venereum (LGV) has reestablished itself as an endemic sexually transmitted infection in the United Kingdom and elsewhere in Europe and North America over the last decade. Current guidelines suggest treatment with 21 days of doxycycline; however, the evidence base for LGV treatment including its duration is very limited. Methods We conducted a retrospective review in 2 central London genitourinary medicine clinics of men who have sex with men (MSM) with LGV in whom less than 21 days of doxycycline was used initially. Results Sixty MSM were treated initially with less than 21 days of doxycycline, of whom 50 (83%) were prescribed a 7-day course. Fifty percent of patients were asymptomatic, with the rest having rectal or other symptoms. Fifty-nine (97%) of 60 had a negative test of cure for LGV at a median of 31 days (7–200 days). Reinfection as opposed to treatment failure was considered likely in the patient testing positive. A second test of cure at a median of 139 days later (37–638 days) was completed in 30 patients, of whom 28 (93%) were negative for LGV. Conclusions Seven to 14 days of doxycycline is effective in most cases of LGV with negative TOCs in 59 of 60 patients. These data suggest that 7 days of doxycycline is effective in achieving cure of rectal LGV in most MSM. There is a case for a randomized controlled trial of LGV treatment including a 7-day regimen of doxycycline.