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BackgroundEffectiveness of HIV postexposure prophylaxis (PEPSE) correlates with speed of uptake following HIV exposure. Time to first dose has not improved in the UK for over 10 years. On-demand pre-exposure prophylaxis (PrEP) has shown that people can self-start medication for HIV prevention.We hypothesised that advanced provision of PEPSE (HOME PEPSE) for men who have sex with men (MSM) to self- initiate would reduce time to first dose following HIV exposure.MethodsPhase IV, randomised, prospective, 48-week, open-label study was carried out. MSM at medium risk of acquiring HIV were randomised (1:1) to immediate or deferred standard of care (SOC) HOME PEPSE. Every 12 weeks, participants self-completed mental health/risk behaviour surveys and had HIV/sexually transmitted infection (STI) testing.HOME PEPSE comprised a 5-day pack of emtricitabine/tenofovir disoproxil fumarate/maraviroc 600 mg once daily initiated following potential exposure to HIV. If taken, participants completed a risk survey; PEPSE continuation was physician directed. Primary outcome was time from potential exposure to HIV to first PEPSE dose.Findings139 participants randomised 1:1; 69 to immediate HOME PEPSE and 70 to deferred HOME PEPSE. Median age 30 years (IQR 26–39), 75% white, 55% UK born and 72% university educated. 31 in HOME PEPSE and 15 in SOC arm initiated PEPSE. Uptake of HOME PEPSE was appropriate in 27/31 cases (87%, 95% CI: 71% to 95%). Median time from exposure to first dose was 7.3 hours (3.0, 20.9) for HOME PEPSE and 28.5 hours (17.3, 34.0) for SOC (pNo significant differences in missed opportunities for PEPSE uptake, sexual behaviour or bacterial STI infections between treatment arms.InterpretationHOME PEPSE reduced the time from exposure to first-dose PEPSE by 21+ hours, with no impact on safety. This significantly improves the efficacy of PEPSE and provides an option for people declining PrEP.

Background The contribution of HIV to COVID‐19 outcomes in hospitalized inpatients remains unclear. We conducted a multi‐centre, retrospective matched cohort study of SARS‐CoV‐2 PCR‐positive hospital inpatients analysed by HIV status. Methods HIV‐negative patients were matched to people living with HIV (PLWH) admitted from 1 February 2020 to 31 May 2020 up to a 3:1 ratio by the following: hospital site, SARS‐CoV‐2 test date ± 7 days, age ± 5 years, gender, and index of multiple deprivation decile ± 1. The primary objective was clinical improvement (two‐point improvement or better on a seven‐point ordinal scale) or hospital discharge by day 28, whichever was earlier. Results A total of 68 PLWH and 181 HIV‐negative comparators were included. In unadjusted analyses, PLWH had a reduced hazard of achieving clinical improvement or discharge [adjusted hazard ratio (aHR) = 0.57, 95% confidence interval (CI): 0.39–0.85, p = 0.005], but this association was ameliorated (aHR = 0.70, 95% CI: 0.43–1.17, p = 0.18) after additional adjustment for ethnicity, frailty, baseline hypoxaemia, duration of symptoms prior to baseline, body mass index (BMI) categories and comorbidities. Baseline frailty (aHR = 0.79, 95% CI: 0.65–0.95, p = 0.011), malignancy (aHR = 0.37, 95% CI 0.17, 0.82, p = 0.014) remained associated with poorer outcomes. The PLWH were more likely to be of black, Asian and minority ethnic background (75.0% vs 48.6%, p = 0.0002), higher median clinical frailty score [3 × interquartile range (IQR): 2–5 vs, 2 × IQR: 1–4, p = 0.0069), and to have a non‐significantly higher proportion of active malignancy (14.4% vs 9.9%, p = 0.29). Conclusions Adjusting for confounding comorbidities and demographics in a matched cohort ameliorated differences in outcomes of PLWH hospitalized with COVID‐19, highlighting the importance of an appropriate comparison group when assessing outcomes of PLWH hospitalized with COVID‐19.

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., Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum (TPA), and incidence has risen recently in many countries. Here, Beale et al. provide whole-genome TPA sequences from 73 clinical samples and show how antimicrobial resistance emerged independently in circulating lineages.

Background: It is unclear from epidemiological data for COVID-19 infections, whether people living with HIV (PLWH) have a different outcomes compared to the general population. We conducted a multi-centre, retrospective matched cohort study of SARS-CoV-2 PCR-positive hospital inpatients analysed by HIV-status. Methods: HIV-negative patients were matched to PLWH admitted to hospital before 31 st May 2020, with a 3:1 ratio by: hospital site, SARS-CoV-2 test date +/- 7 days, age +/- 5 years, gender, and index of multiple deprivation decile (IMDD) +/- 1. The primary objective was clinical improvement (≥2-point improvement on a 7-point ordinal scale) or hospital discharge by day 28, whichever was earlier. Results: 68 PLWH and 181 HIV-negative comparators were included. After adjustment for ethnicity, frailty, baseline hypoxia, duration of symptoms prior to baseline, body mass index categories, and comorbidities (hypertension, chronic cardiac disease, chronic lung disease, active malignancy, diabetes, and chronic renal disease), the effect size of HIV status was not associated with time to clinical improvement or discharge from hospital (aHR 0.70, 95%CI 0.43, 1.17; p=0.18), despite unadjusted hazards of PLWH achieving the primary outcome being 43% lower (p=0.005). Baseline frailty (aHR=0.79; 95%CI 0.65, 0.95; p=0.011), malignancy (aHR=0.37; 95%CI 0.17, 0.82; p=0.014) remained associated with poorer outcomes. PLWH were more likely of black and minority ethnicities (75.0% vs 48.6%, p=0.0002), higher median clinical frailty score (3 IQR 2-5 vs 2 IQR 1-4, p=0.0069), higher proportion of active malignancy (14.4% vs 9.9%, p=0.29). Median body mass index (BMI) was lower amongst PLWH (27.7 IQR 23.9-32.3 vs 29.4 IQR 24.7-34.3, p=0.19). Median CD4 count of PLWH was 352cells/µL (IQR 235-619) and 95.7% had suppressed viral loads

Background Infectious syphilis incidence is increasing worldwide, particularly amongst men who have sex with men (MSM). We report a case series of two patients with a rare presentation of syphilitic pneumonitis masquerading as thoracic malignancy. Methods Patient history review via electronic records. Results Case 1- 54 year old MSM, HIV diagnosed 2011, CD4 nadir 557 cells/µl, current CD4 861 cells/µl and HIV viral load (VL) undetectable since commencing antiretroviral therapy (ART), presented to emergency department (ED) with pleuritic chest pain and normal oxygen saturation. CT scan demonstrated parenchymal and sub-pleural nodules measuring maximum 13 mm, thought likely to represent malignancy and one lesion had features of an infarct. He started Rivaroxaban in ED and subsequently developed a rash suggestive of evolving syphilis. Rapid plasma reagin (RPR) six weeks after initial presentation was 1:32. Treated with 2 weeks of doxycycline, RPR six weeks later was 1:16 and at five months 1:4. CT scan six weeks post treatment showed almost complete resolution of nodules. Case 2- 38 year old MSM, HIV diagnosed in March 2017, CD4 nadir 65 cells/µl, current CD4 219 cells/µl and VL 109 cells/µl on ART. Kaposi’s sarcoma (KS) diagnosed in 2017, involving skin, lymph nodes and spleen, treated to remission with ART alone. Presented in July 2018 with deranged liver function tests. CT scan showed multiple sub-pleural and parenchymal nodules, largest 11 mm, however no progression of lymphadenopathy or clinical progression of cutaneous KS. RPR 1:512 and resolution to 1:16 three months after treatment with intramuscular Benzathine Penicillin. Radiological resolution of lung nodules occurred after 2 months of treatment. Chemotherapy was avoided. Conclusion Syphilitic pulmonary/pleural nodules resolve with standard antibiotic therapy. Patients with pulmonary nodules usually present to primary care or specialist services where they are investigated for vasculitis/malignancy, but rarely for syphilis. For patients at risk, ruling out syphilis would avoid unnecessary interventions. Disclosure No significant relationships.

Background British guidelines recommend both event-based dosing (EBD) and daily dosing of combined tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM). Access to PrEP in the UK is either through a clinical study with limited capacity or by purchasing online. Dosing schedules are usually self-selected, often without access to professional advice or evidenced-based information. Non-daily dosing is popular as it is believed to be less toxic and more affordable than daily dosing. Methods We describe three cases of HIV acquisition despite use of PrEP. Results All were MSM and had a negative antigen/antibody HIV tests at 3 months of use. Case 1 switched to EBD after one month of daily PrEP. After several months he switched back to daily PrEP and had a positive HIV-1 antibody test six weeks later. Case 2 switched to EBD after 5 months of daily PrEP due to lower frequency of sex. He reported excellent adherence. He had a positive HIV-1 antibody test 4 months later. Case 3 was taking EBD PrEP for a total of 9 months. He had a positive HIV-1 antibody 5 months after his last negative HIV test. This was two months after his last episode of condomless sex. He reported occasional late dosing and some use of recreational drugs. Conclusion It is likely that all three cases became infected while taking event-based PrEP. Two cases switched between daily and EBD due to lower self-perceived risk of HIV or frequency of sex. It is not clear if this may have affected PrEP efficacy. Evidence for effective EBD is strongly dependent on adherence and timing of doses. It is therefore vital that PrEP provision includes objective HIV risk assessment, adherence support and evidence-based dosing information to optimise efficacy. Disclosure No significant relationships.

Background The British Association of Sexual Health and HIV recommends testing for Mycoplasma genitalium (MG) in clinically indicated conditions (CIC) (non-gonococcal urethritis (NGU); epididymitis; pelvic inflammatory disease (PID); contacts of MG; test of cure (TOC)). MG testing was implemented in September 2018 in a large urban sexual health service. We aimed to assess the prevalence and antimicrobial resistance of MG in this clinic population after a 6-weeks embedding period. Methods All patients diagnosed with a CIC and tested for MG between 28/10/2018-18/12/2018 were included. MG testing was performed using Aptima Mycoplasma genitalium assay (AMG; Hologic); confirmatory testing and resistance testing for macrolides and fluoroquinolones was performed at the Public Health England reference laboratory. Results The 371 individuals tested for MG were predominantly male (77%), heterosexual (78%) and Caucasian (46%) and 85% tested per guidance. 18% were positive for MG. 38% (25/65) were positive using AMG but had negative confirmatory test and no resistance results. 18% with MG were co-infected with another sexually transmitted infection (9 chlamydia; 2 gonorrhoea; 2 trichomonas). The prevalence of MG by testing indication was: contacts of MG (33%, 11/33), TOC (25%, 3/12), NGU/epididymitis (17%, 38/229), PID/cervicitis (11%, 5/44) and inappropriately tested (14%, 7/51). 38% of MG had resistance; 34% macrolides; 8% fluoroquinolones; 3% both. Macrolide resistance was identified on the 23SrRNA gene at loci A2058G (45%) and A209G (55%), all fluoroquinolone was on the parC gene. Conclusion We report a high MG prevalence in this population with high rates of resistance, the majority of which is macrolide. We recommend resistance guided therapy in view of high macrolide and fluoroquinolone resistance. Positive RNA detection with negative DNA detection is concerning and may either represent very low bacterial loads, a biological false positive result of AMG or a false negative result of the confirmatory test. Disclosure No significant relationships.

OBJECTIVES: To assess clinical service value of STI point-of-care test (POCT) use in a 'sample first' clinical pathway (patients providing samples on arrival at clinic, before clinician consultation). Specific outcomes were: patient acceptability; whether a rapid nucleic acid amplification test (NAAT) for Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) could be used as a POCT in practice; feasibility of non-NAAT POCT implementation for Trichomonas vaginalis (TV) and bacterial vaginosis (BV); impact on patient diagnosis and treatment. METHODS: Service evaluation in a south London sexual health clinic. Symptomatic female and male patients and sexual contacts of CT/NG-positive individuals provided samples for diagnostic testing on clinic arrival, prior to clinical consultation. Tests included routine culture and microscopy; CT/NG (GeneXpert) NAAT; non-NAAT POCTs for TV and BV. RESULTS: All 70 (35 males, 35 females) patients approached participated. The 'sample first' pathway was acceptable, with >90% reporting they were happy to give samples on arrival and receive results in the same visit. Non-NAAT POCT results were available for all patients prior to leaving clinic; rapid CT/NG results were available for only 21.4% (15/70; 5 males, 10 females) of patients prior to leaving clinic. Known negative CT/NG results led to two females avoiding presumptive treatment, and one male receiving treatment directed at possible Mycoplasma genitalium infection causing non-gonococcal urethritis. Non-NAAT POCTs detected more positives than routine microscopy (TV 3 vs 2; BV 24 vs 7), resulting in more patients receiving treatment. CONCLUSIONS: A 'sample first' clinical pathway to enable multiple POCT use was acceptable to patients and feasible in a busy sexual health clinic, but rapid CT/NG processing time was too long to enable POCT use. There is need for further development to improve test processing times to enable POC use of rapid NAATs.

Background Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. Objectives To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. Methods A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. Results M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. Conclusion A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

Background Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30 min. Methods Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested “fresh” within 10 days of collection, or “frozen” at − 80 °C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. Results CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5–99.5), 97.7% (95%CI: 96.3–98.7), 76.6% (95%CI: 64.3–86.2) and 99.7% (95%CI: 98.9–100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. Conclusions The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care., Highlights • The io® CT assay's sensitivity is comparable to that of laboratory-based assays commonly used for Chlamydia detection. • The specificity as shown is this study is at the lower end of the range reported for laboratory-based assays. • The resulting positive predictive value, in this population, indicates that a targeted testing approach may be optimal. Until now, there have been no ≤ 30-min point-of-care test (POCT) nucleic acid amplification tests (NAATs) on the market for detecting Chlamydia trachomatis (CT), despite cost-effectiveness analyses demonstrating they may improve Genito-Urinary Medicine (GUM)/Reproductive and Sexual Health (RSH) clinical care pathway efficiencies and patient outcomes. Our evaluation of the 30-min Atlas Genetics io® CT NAAT POCT, on vaginal swabs from women attending four GUM/RSH clinics in England, shows that the test's sensitivity (accurately detecting CT-positive infections) is similar to that of laboratory-based NAATs, and its specificity (accurately detecting CT-negative infections) is at the lower end of the laboratory-based NAAT range.

OBJECTIVES: Gram-stained urethral smear (GSUS), the standard point-of-care test for non-gonococcal urethritis (NGU) is operator dependent and poorly specific. The performance of rapid automated urine flow cytometry (AUFC) of first void urine (FVU) white cell counts (UWCC) for predicting Mycoplasma genitalium and Chlamydia trachomatis urethral infections was assessed and its application to asymptomatic infection was evaluated. METHODS: Receiver operating characteristic curve analysis, determining FVU-UWCC threshold for predicting M. genitalium or C. trachomatis infection was performed on 208 'training' samples from symptomatic patients and subsequently validated using 228 additional FVUs obtained from prospective unselected patients. RESULTS: An optimal diagnostic threshold of >29 UWC/µL gave sensitivities and specificities for either infection of 81.5% (95% CI 65.1% to 91.6%) and 85.8% (79.5% to 90.4%), respectively, compared with 86.8% (71.1% to 95%) and 64.7% (56.9% to 71.7%), respectively, for GSUS, using the training set samples. FVU-UWCC demonstrated sensitivities and specificities of 69.2% (95% CI 48.1% to 84.9%) and 92% (87.2% to 95.2%), respectively, when using validation samples. In asymptomatic patients where GSUS was not used, AUFC would have enabled more infections to be detected compared with clinical considerations only (71.4% vs 28.6%; p=0.03). The correlation between UWCC and bacterial load was stronger for M. genitalium compared with C. trachomatis (τ=0.426, p≤0.001 vs τ=0.295, p=0.022, respectively). CONCLUSIONS: AUFC offers improved specificity over microscopy for predicting C. trachomatis or M. genitalium infection. Universal AUFC may enable non-invasive diagnosis of asymptomatic NGU at the PoC. The degree of urethral inflammation exhibits a stronger association with pathogen load for M. genitalium compared with C. trachomatis.

BackgroundRapid Point-Of-Care Tests (POCTs) forChlamydia trachomatis(CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io®single module system (Atlas Genetics Ltd) runs clinical samples through a microfluidic CT cartridge, delivering results in 30 minutes. We evaluated its performance on female genital samples in four UK Genito-Urinary Medicine (GUM)/RSH clinics.MethodsProspective diagnostic accuracy study, using BD ProbeTec CT/GC assay as the routine clinic nucleic acid amplification test (NAAT) as the initial comparator test, and the QIAgen Artus CT assay to resolve discrepancies. In these instances, the reference standard was defined as the resolved result when two out of three assay results concurred. Female participants aged ≥16 provided additional-to-routine self-collected vulvovaginal swabs. Samples were tested fresh with the io®CT assay within 7 days of collection, or were frozen at −80°C for later testing. Participant clinical, demographic and behavioural characteristics were collected to assess risk factors associated with CT infection.ResultsOf 785 participants recruited, final analyses were conducted on 709 (90.3%). CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io®CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). There was no significant difference in performance measures between fresh and frozen samples, or between symptomatic and asymptomatic participants (p>0.05). The only risk factor associated with CT infection was being a sexual contact of an individual with CT.ConclusionsThe io®CT-assay is the only 30-minute, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care. Future research is required to evaluate acceptability by clinicians and patients in GUM/RSH clinics, impact on clinical pathways and patient management, and cost-effectiveness.

Introduction Applying bacterial 16S rRNA profiling we investigated whether species in first void urine (FVU) differed between men presenting with urethritis symptoms with and without urethral inflammation. Methods 443 patients prospectively attending a London sexual health clinic were classified, based on clinical presentation and Gram stain as: symptomatic urethritis (URE); symptomatic non-urethritis (SYM); and asymptomatic (ASP). Residual FVU’s were tested for [K1] Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) and subjected to bacterial 16S rRNA profiling (variable region v1-2) Differences in bacterial oligotypes across samples were described using partial least square discriminant analysis tested using permutational multivariate analysis of variance (PERMANOVA). The hypothesis tested was: URE have distinct urinary bacterial 16S rRNA profiles compared to SYM and ASP. Results 286/443 samples met quality control criteria. Among URE [n=79], SYM [n=83], and ASP [n=124], CT, MG, NG and TV prevalence’s were: 12.7% (95 CI 6.6–22.5), 13.9% (95CI 7.5–24), 8.9% (95CI 3.9–7.5), 1.3% (95CI 0.1–7.8); 2.4% (95CI 0.4–9.2), 2.4% (95CI 0.4–9.2), 1.2% (95CI 0.1–7.5); 2.4% (95CI 0.6–7.4), 5.7% (95CI 2.5–11.8), NG not detected, 0.8% (95CI 0–5.1) respectively. Lactobacillus iners was the most abundant oligotype observed in all groups. Streptococcus agalactiae and S. anginosus were highly dominant in ASP along with S. mitis, which was relatively increased in both ASP and SYM. A decreased relative abundance of these oligotypes was observed in URE cases. A significant difference in oligotype populations was observed between URE and SYM (PERMANOVA test p=0.0072, F2.182), but not between SYM and ASP (PERMANOVA test [JW2] p=0.0.1797, F1.601). Conclusion SYM and ASP oligotype populations were dominated by Lactobacillus and Streptococcus species. Microbiota observed in FVU samples of symptomatic patients with microscopy confirmed urethritis (URE) were distinct to those with symptoms but no urethritis on microscopy (SYM).

Sexually transmitted infections (STIs) continue to be a major public health concern in the United Kingdom (UK). Epidemiological models have shown that narrowing the time between STI diagnosis and treatment may reduce the population burden of infection, and rapid, accurate point-of-care tests (POCTs) have potential for increasing correct treatment and mitigating the spread of antimicrobial resistance (AMR). We developed the Precise social science programme to incorporate clinician and patient opinions on potential designs and implementation of new POCTs for multiple STIs and AMR detection. We conducted qualitative research, consisting of informal interviews with clinicians and semi-structured in-depth interviews with patients, in six sexual health clinics in the UK. Interviews with clinicians focused on how the new POCTs would likely be implemented into clinical care; these new clinical pathways were then posed to patients in in-depth interviews. Patient interviews showed acceptability of POCTs, however, willingness to wait in clinic for test results depended on the context of patients' sexual healthcare seeking. Patients reporting frequent healthcare visits often based their expectations and opinions of services and POCTs on previous visits. Patients' suggestions for implementation of POCTs included provision of information on service changes and targeting tests to patients concerned they are infected. Our data suggests that patients may accept new POCT pathways if they are given information on these changes prior to attending services and to consider implementing POCTs among patients who are anxious about their infection status and/or who are experiencing symptoms.

Objective: To determine the prevalence of rectal chlamydia infection in a cohort of men who have sex with men (MSM) and the proportion of infection that would be missed without routine screening. Methods: MSM presenting to four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust between 1 November 2005 and 29 September 2006 were offered testing for rectal chlamydia infection in addition to their routine screen for sexually transmitted infections (STIs). Chlamydia trachomatis (CT) tests were performed using the Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re-tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the result and identify lymphogranuloma venereum (LGV)-associated serovars. Results: A total of 3076 men were screened. We found an 8.2% prevalence of infection with CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections (69.2%, (171/247)) were asymptomatic and would have been missed if routine screening had not been undertaken. Of the samples re-tested, 94.2% (227/242) rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36 cases of LGV were identified. Conclusion: Our data show a high rate of rectal chlamydia infection, in the majority of cases it was asymptomatic. We recommend routine screening for rectal chlamydia in men at risk, as this may represent an important reservoir for the onward transmission of infection.

Mycoplasma genitalium infections were as frequent a cause of nongonococcal urethritis as Chlamydia trachomatis, had high rates of macrolide-associated genotypic resistance, and were nonclonal, suggesting an established community infection. Detection of genotypic resistance to fluoroquinolones is cause for concern., Background. Empirical antibiotic therapy for nongonococcal urethritis (NGU) and cervicitis is aimed at Chlamydia trachomatis, but Mycoplasma genitalium, which also commonly causes undiagnosed NGU, necessitates treatment with macrolides or fluoroquinolones rather than doxycycline, the preferred chlamydia treatment. Prevalence of M. genitalium and associated genotypic markers of macrolide and fluoroquinolone resistance among men symptomatic of urethritis were investigated. Genetic diversity of M. genitalium populations was determined to infer whether findings were applicable beyond our setting. Methods. Mycoplasma genitalium and other NGU pathogens were detected using nucleic acid amplification methods, and DNA sequencing was used to detect genotypic resistance markers of macrolide and fluoroquinolone antibiotics in 23S ribosomal RNA, gyrA, gyrB, and parC genes. MG191 single-nucleotide polymorphism typing and MG309 variable number tandem analysis were combined to assign a dual locus sequence type (DLST) to each positive sample. Results. Among 217 men, M. genitalium prevalence was 16.7% (95% confidence interval [CI], 9.5%–24.0%) and C. trachomatis prevalence was 14.7% (95% CI, 7.8%–21.6%) in NGU cases. Nine of 22 (41%; 95% CI, 20%–62%) patients with M. genitalium were infected with DLSTs possessing genotypic macrolide resistance and 1 patient was infected with a DLST having genotypic fluoroquinolone resistance. Typing assigned M. genitalium DLSTs to 2 major clusters, broadly distributed among previously typed international strains. Genotypic macrolide resistance was spread within these 2 clusters. Conclusions. Mycoplasma genitalium is a frequent undiagnosed cause of NGU in this population with rates of macrolide resistance higher than those previously documented. Current guidelines for routine testing and empirical treatment of NGU should be modified to reduce treatment failure of NGU and the development of further resistance.

Introduction Sexual behaviour and vaginal practices impact on vaginal pathology, but accurately capturing such data for multi-site clinical studies is logistically difficult. Computer assisted self-interviews (CASI), are useful for capturing sensitive information for community surveys but require programming expertise or expensive software. We piloted an open-source software designed internet-based CASI, using previously validated questions for a multi-site clinical study on the vaginal microbiome. Methods The CASI question-structure was constructed from the third UK National Survey of Sexual Attitudes and Lifestyles using LimeSurvey open source software and consisted of 71 questions, delivered through a responsive algorithm, covering demographics, sexual behaviour, vaginal practices, contraception and life-time smoking history. Patients could decline questions and the CASI was delivered to participants online. Bacterial vaginosis (BV) status was determined by Nugent scores from Gram-stained lateral vaginal swab smears. Results Data from 155 women with available Nugent scores were included. Mean time to completing CASI was 303 s (Range: 111.76 -670.15 s 95% CI ±16.83 s). There were no missing data. The question most participants declined to answer was “number of one-off partners” (14 participants, 9%). White ethnicity and oestrogen-based contraceptives were inversely related with BV (Odds ratios (OR): 0.33 [95% CI: 0.16–0.67] and 0.41 [0.17–0.97] respectively) and lifetime smoking of >1 pack-years and regular vaginal douching were directly related with BV (OR: 2.56 [1.21–5.41] and 2.03 [1.01–4.09] respectively). Nearly 50% of women reported daily vaginal douching and >90% reported using feminine care products in the preceding month. Conclusion The CASI delivered a complete dataset, the findings from which were consistent with published associations of BV, demonstrating robustness. Web-based CASI is an efficient method of collecting sensitive sexual and behavioural data within a complex clinical study, from patients recruited in busy clinical settings, and can be developed using open-source questionnaire software without the need for coding expertise. Disclosure of interest statement This work was done as part of the Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608). The funding sources had no involvement in the study design or conduct; the collection, analysis and interpretation of data; the preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication. The views expressed are those of the authors and not necessarily those of the NHS, the MRC, or St George’s, University of London. The authors declare no competing interests.

Introduction There is a lack of data on the sexual behaviour of patients between being tested for chlamydia, receiving the test result, and being treated. This time-period may be important in the transmission of chlamydia, as infection could continue to be spread to sexual partners whilst awaiting the test result and treatment. We aimed to investigate the sexual behaviours of patients in this time-period in order to investigate the benefits a point-of-care test (POCT) might bring to clinical practice. Methods A cross-sectional clinical audit of Genito-Urinary Medicine (GUM) clinic attendees in England. Clinic staff conducted a notes review of patients returning for chlamydia treatment following a positive chlamydia test result, and of age- and sex-matched chlamydia negatives attending for initial consultation. Initial consultation data were available for all patients; data on behaviour between test and treatment were available only for chlamydia-positives. The data also served as a sexual history taking audit for the GUM clinics, following British Association of Sexual Health and HIV (BASHH) guidelines. Results Five of nine GUM clinics approached participated (July–December 2014). The sexual history BASHH auditable outcomes completion rates varied from 0–100%. 775 patients (442 females, 353 males) were included in analyses. Males with 2–4 partners, and those who reported never using a condom, were more likely to be chlamydia positive. For 21/143 (14.7%) positive patients who provided data, last new sexual contact was in the period between test and treatment. Conclusion The BASHH 97% data recording target was only consistently met for one of six auditable outcomes, indicating required improvements in sexual history recording by GUM clinics. Patients continue to form new sexual partnerships whilst awaiting chlamydia test results, allowing for the possibility of infecting new sexual partners. POCTs which remove the test to treatment delay could prevent this onward transmission.

Background/introduction There is a lack of data on the sexual behaviour of patients between being tested for chlamydia, receiving the test result, and being treated. This time-period may be important in the transmission of chlamydia, as infection could continue to be spread to sexual partners whilst awaiting the test result and treatment. Aim(s)/objectives To investigate the sexual behaviours of patients between the time of being tested for chlamydia and receiving test result and treatment in order to investigate the benefits that a point-of-care test (POCT) might bring to clinical practice. Methods We conducted a cross-sectional clinical audit of GUM clinic attendees. Clinic staff conducted a notes review of patients returning for chlamydia treatment following a positive chlamydia test result, and of age- and sex-matched chlamydia negatives. The data also served as an audit for the GUM clinics, following BASHH guidelines. Results Five of nine GUM clinics approached participated, in July–December 2014. Data from 775 patients were included in analyses, 365 of whom were chlamydia-positive. Males with 2–4 partners, and those who reported never using a condom, were more likely to be chlamydia positive. For 21/143 (14.7%) positive patients who provided data, last new sexual contact was in the period between test and treatment. Data were missing on condom use (22%) and recent new partners (81%). Discussion/conclusion Patients continue to form new sexual partnerships whilst awaiting chlamydia test results, allowing for the possibility of infecting new sexual partners. POCTs which remove the test to treatment delay could prevent this onward transmission.

Background/introduction Control of STIs is challenged by inadequate access to prompt diagnosis and treatment for patients and partners. Novel point-of-care diagnostics have real potential to address some of these challenges but their robust evaluation, and hence utility, is hampered by the ethics and regulatory landscape that confronts industry and academia. Aim(s)/objectives To develop a diagnostics and clinical facility to deliver high-quality, time-efficient diagnostic evaluations for STIs. Methods A multi-institutional and disciplinary group ( e STI 2 ) including clinical, public health and social scientists, microbiologists, clinicians, trial coordinators, and North American and European regulatory expertise was established. An ‘overarching’ ethics, favourable costing, and regulatory framework was carefully developed and put in place to enable any new diagnostic evaluation involving residual and/or additional-to-routine patient-consented samples to start promptly without requiring lengthy ethics applications. Strong working relationships with multiple GUM clinics were developed to overcome the potential for clinic fatigue, and Good Clinical Laboratory Practice Standard Operating Procedures were enabled. Results Since February 2012, the network has conducted several evaluations with both academia and industry, spanning initial ‘proof of concept’ projects using residual samples, multi-site diagnostic evaluations involving >800 additional-to-routine patient samples completed in four months, and service evaluations of CE-marked assays. A diagnostic evaluation to support an application for regulatory approval will be taking place in 2015. Discussion/conclusion The development of a diagnostic facility for STIs that fast-tracks high quality diagnostic evaluations is feasible and has potential for supporting promising diagnostic technologies towards NHS adoption.

Background There is currently no reliable indicator of inflammation available for the evaluation of genital tract syndromes. We investigated the association of urinary calprotectin concentration, an innate immune system mediator protein, with urethritis. Methods First catch urine specimens from men with and without urethritis (> 10 neutrophils/high power field of urethral smears) were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) by nucleic acid amplification tests (NAAT). Supernatants from these samples were tested in duplicate by ELISA for human calprotectin. Data were analysed using Spearman’s coefficient of rank correlation (rho) and ROC curves. Results 159 urinary supernatants were tested. 54/159 had urethritis; 35/159 were NAAT positive for any of CT, NG, MG or TV of whom 27/35 had urethritis; 97/159 had no urethritis and were NAAT negative for all 4 pathogens. The correlation coefficient (rho) for calprotectin concentration and presence of urethritis/infection was 0.529 (95% CI: 0.407–0.633; p Conclusion Urinary calprotectin had similar sensitivity and specificity for common urethral pathogens as urethral microscopy. Low calprotectin concentration correlated well with the absence of inflammation. Use of the assay is currently limited by the unknown dilution effect of urine in estimating urethral calprotectin concentrations but calprotectin is a promising biomarker of inflammation in investigating reproductive tract infections (RTI) of different aetiologies particularly where microscopy may not be available, such as in community settings.

Background Previously, we demonstrated that urinary white cell count increases in proportion to pathogen load in cases of urethritis caused by Mycoplasma genitalium but not Chlamydia trachomatis . We further investigated urethritis pathogenesis caused by these organisms by comparing concentrations of 23 cytokines present within first void urine (FVU) specimens of male urethritis cases. Methods FVUs from 52 symptomatic male patients (all underwent Gram stain urethral smear) were collected and patients stratified into those with non-specific urethritis (n = 12), M. genitalium urethritis (n = 13), C. trachomatis urethritis (n = 14) and non-urethritis controls (n = 13). Cytokines measurements from FVUs specimens were obtained using a Human 30-Plex Luminex assay. Concentrations were obtained for 23 of the 30 cytokines analysed and compared between the four groups using multivariate ANOVA. Results Overall, there was a significant difference in urinary cytokine profile between groups (p = 0.042). For individual cytokines, clinical group was associated with differences in concentrations of IL-1β (p = 0.007), GCSF (p = 0.042), CCL11 (p = 0.012), MIP-1α (p = 0.029), TNF-α (p = 0.026), IL-7 (p = 0.029), EGF (p = 0.030), VEGF (p = 0.049) and IFNa (p = 0.008). When compared with uninfected non-urethritis controls, cytokine concentrations in: M. genitalium samples, were increased for IL-1β (p = 0.017), GCSF (p = 0.010) but decreased for EGF (p = 0.017); C. trachomatis samples, were decreased for EGF (p = 0.049); and in non-specific urethritis samples, were increased for CCL5 (p = 0.049), IL-1β (p = 0.05), IL-1RA (p = 0.033) and decreased for EGF (p = 0.032). No significant differences were demonstrated in cytokine concentrations between C. trachomatis and M. genitalium groups. Conclusion The increased levels of pro-inflammatory cytokines present in the urethritis groups when compared to non-urethritis controls reflect the acute inflammatory state. The data suggests that M. genitalium genital infection may be associated with a discrete mucosal immunological profile potentially explaining the link between cellular inflammatory response and bacterial load, previously observed

Background Excluding HIV testing, point-of-care tests (POCTs) for STIs are not routinely available in UK sexual health clinics, apart from microscopy which has limited sensitivity, is observer dependent and often only allows for imprecise syndromic treatment. From sample-to-result for routine Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) molecular tests usually takes several days. Molecular and non-molecular STI-POCTs, including automated urine flow cytometry, may improve patient pathways, obviate the need for microscopy and personalise treatment effectively. Methods This was a clinic evaluation using a rapid molecular test for CT/NG (Cepheid GeneXpert; 90 minute turnaround) combined with non-molecular POCTs for Trichomonas vaginalis (OSOM), Bacterial vaginosis (Alere VS-Sense) and automated urinary white cell count (WCC) for urethritis (Alere UF-100). Contacts of CT/NG, males with symptoms of urethritis, and symptomatic females provided samples immediately on arrival, prior to clinical consultation. Patients also concurrently had routine culture and microscopy. Results Of eighteen patients providing feedback, all but one found providing samples on arrival acceptable; waiting 2 hours was seen as too long. All patients waited for the results of their non-molecular POCT but only three of nineteen men waited for the rapid GeneXpert results, despite six being positive. All positive patients were given appropriate empirical treatment. A third of women waited despite all being GeneXpert negative. The TV and BV POCTs detected more cases than microscopy, and urethral smear detected more urethritis than automated WCC. Conclusion Despite the provision of genital samples on arrival being acceptable and patients liking the idea of receiving results in the same clinical visit, only a quarter of all patients waited for their GeneXpert results. Larger studies to evaluate the clinical impact of rapid molecular testing in clinic are required before any large scale implementation is considered.