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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., Competing Interests: ADREU has received funding from Binx Health (formerly Atlas Genetics Ltd), Alere, Cepheid, SpeedDx, Mologic, Revolugen and Sekisui. SSF and EHE have been members of the BD Diagnostics Advisory Panel on UK Provision of Sexual Health Services. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)., Methods: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert., Results: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female)., Conclusions: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Evidence on optimal methods for providing STI test results is lacking. We evaluated an online results service, developed as part of an eSexual Health Clinic (eSHC)., Methods: We evaluated the online results service using a mixed-methods approach within large exploratory studies of the eSHC. Participants were chlamydia- positive and negative users of online postal self-sampling services in six National Chlamydia Screening Programme (NCSP) areas and chlamydia-positive patients from two genitourinary medicine (GUM) clinics between 21 July 2014 and 13 March 2015. Participants received a discreetly worded National Health Service 'NHS no-reply' text message (SMS) informing them that their test results were ready and providing a weblink to a secure website. Participants logged in with their date of birth and mobile telephone or clinic number. Chlamydia-positive patients were offered online management. All interactions with the eSHC system were automatically logged and their timing recorded. Post-treatment, a service evaluation survey (n=152) and qualitative interviews (n=36) were conducted by telephone. Chlamydia-negative patients were offered a short online survey (n=274). Data were integrated., Results: 92% (134/146) of NCSP chlamydia-positive patients, 82% (161/197) of GUM chlamydia-positive patients and 89% (1776/1997) of NCSP chlamydia-negative participants accessed test results within 7 days. 91% of chlamydia-positive patients were happy with the results service; 64% of those who had tested previously found the results service better or much better than previous experiences. 90% of chlamydia-negative survey participants agreed they would be happy to receive results this way in the future. Interviewees described accessing results with ease and appreciated the privacy and control the two-step process gave them., Conclusion: A discreet SMS to alert users/patients that results are available, followed by provision of results via a secure website, was highly acceptable, irrespective of test result and testing history. The eSHC results service afforded users privacy and control over when they viewed results without compromising access., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing., Design: Modelling study., Setting: Genitourinary medicine (GUM) services in England., Population: A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection., Interventions: The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates., Primary and Secondary Outcome Measures: Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances., Results: In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC., Conclusions: Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest Form and declare financial support from Innovate UK; EJA, SEH, MJH are employees of Aquarius Population Health (APH), which reports grants from Innovate UK grant to Atlas Genetics, during the conduct of the study; other from Cepheid, St Georges University of London, Enigma Diagnostics and AstraZeneca, on STI and POC research outside the submitted work; RMB is a Lecturer and Programme Director of Economics at St. Angela’s College Sligo/NUI Galway and an academic staff member of the Health Economics and Policy Analysis Centre (HEPAC) at NUI Galway, providing health economic support to Aquarius Population Health on an ad hoc consultancy basis. STS, EH-E, SSF are members of the Applied Diagnostic Research and Evaluation Unit at St George’s, University of London, which has received funding from Atlas Genetics, Alere, Cepheid, SpeeDx and Sekisui. STS has received NIHR funding to develop a POCT with Atlas., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI)., Design: Systematic review and four meta-analyses conducted using random-effects modelling., Data Sources: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017., Eligibility Criteria: Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics., Results: Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10)., Conclusions: High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: In the UK, people of black ethnicity experience a disproportionate burden of HIV and STI. We aimed to assess the association of ethnicity with sexual behaviour and sexual health among women and heterosexual men attending genitourinary medicine (GUM) clinics in England., Methods: The Attitudes to and Understanding of Risk of Acquisition of HIV is a cross-sectional, self-administered questionnaire study of HIV negative people recruited from 20 GUM clinics in England, 2013-2014. Modified Poisson regression with robust SEs was used to calculate adjusted prevalence ratios (aPR) for the association between ethnicity and various sexual risk behaviours, adjusted for age, study region, education and relationship status., Results: Questionnaires were completed by 1146 individuals, 676 women and 470 heterosexual men. Ethnicity was recorded for 1131 (98.8%) participants: 550 (48.6%) black/mixed African, 168 (14.9%) black/mixed Caribbean, 308 (27.2%) white ethnic groups, 105 (9.3%) other ethnicity. Compared with women from white ethnic groups, black/mixed African women were less likely to report condomless sex with a non-regular partner (aPR (95% CI) 0.67 (0.51 to 0.88)), black/mixed African and black/mixed Caribbean women were less likely to report two or more new partners (0.42 (0.32 to 0.55) and 0.44 (0.29 to 0.65), respectively), and black/mixed Caribbean women were more likely to report an STI diagnosis (1.56 (1.00 to 2.42)). Compared with men from white ethnic groups, black/mixed Caribbean men were more likely to report an STI diagnosis (1.91 (1.20 to 3.04)), but did not report risk behaviours more frequently. Men and women of black/mixed Caribbean ethnicity remained more likely to report STI history after adjustment for sexual risk behaviours., Discussion: Risk behaviours were reported less frequently by women of black ethnicity; however, history of STI was more prevalent among black/mixed Caribbean women. In black/mixed Caribbean men, higher STI history was not explained by ethnic variation in reported risk behaviours. The association between STI and black/mixed Caribbean ethnicity remained after adjustment for risk behaviours., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Non-specific genital infection (NSGI; non- Chlamydia trachomatis , non- Neisseria gonorrhoeae -associated urethritis) is a common diagnosis in symptomatic heterosexual men attending UK sexual health clinics (SHCs). but little is known about the psychosocial impact of this diagnosis., Methods: We conducted an observational study among symptomatic heterosexual men attending SHCs to evaluate the psychosocial impact of an NSGI diagnosis compared with a diagnosis of Chlamydia trachomatis (CT), Neisseria gonorrhoeae or no abnormalities detected focusing on the feasibility of our study methodology. Participants completed a computer-assisted self-interviewing (CASI) including two validated measures of psychosocial impact: the EQ-5D-5L health-related quality of life and Rosenberg Self-Esteem Scale, before diagnostic testing and 2 weeks after receiving test results (follow-up 1 (FU-1)) and a qualitative interview. We compared scores between diagnostic groups using paired t-tests, qualitative data were analysed thematically and feasibility was assessed by process analysis., Results: 60 men completed the baseline CASI (75% response rate). 46 (76.6%) were eligible for follow-up; 11/46 (23.9%) completed the follow-up CASI, and 3/11 (27.3%) completed the qualitative interview. 81.7% of all participants left CASI feedback at baseline: 73.5% reported the questionnaire as 'fine' or 'very good'. Qualitative interview participants reported the study was acceptable. Compared with baseline, among patients completing FU-1, only patients with a diagnosis of NSGI (p<0.05) or CT (p<0.05) showed increased EQ-5D-5L Index, whereas patients with a diagnosis of NSGI (p=0.05) showed decreased mean Rosenberg Self-Esteem Scale score., Conclusions: Although most participants indicated study acceptability at baseline, and we employed measures to increase retention (CASI questionnaires, reminder messages and a focus on men's health), we experienced high loss to follow-up. We found that heterosexual men attending SHCs with symptoms of urethritis experience both positive and negative psychosocial impacts following their clinic attendance, which warrants further investigation., Competing Interests: Competing interests: The Applied Diagnostic Research and Evaluation Unit at St George’s, University of London (STS, EMH-E, SF and AP) receives funding from the National Institute of Health Research (NIHR) i4i Programme (grant number II-LB-0214-20005), Atlas Genetics, Alere, Hologic Cepheid, SpeeDx, Sekisui and Becton Dickinson to develop Point of Care Tests for STIs., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: We developed the eSexual Health Clinic (eSHC), an innovative, complex clinical and public health intervention, embedded within a specialist sexual health service. Patients with genital chlamydia access their results online and are offered medical management via an automated online clinical consultation, leading to antibiotic collection from community pharmacy. A telephone helpline, staffed by Sexual Health Advisers, is available to support patients and direct them to conventional services if appropriate. We sought to understand how patients used this ehealth intervention., Methods: Within exploratory studies of the eSHC (2014-2015), we conducted in-depth interviews with a purposive sample of 36 patients diagnosed with chlamydia, who had chosen to use the eSHC (age 18-35, 20 female, 16 male). Thematic analysis was conducted., Results: Participants described choosing to use this ehealth intervention to obtain treatment rapidly, conveniently and privately, within busy lifestyles that hindered clinic access. They described completing the online consultation promptly, discreetly and with ease. The information provided online was considered comprehensive, reassuring and helpful, but some overlooked it in their haste to obtain treatment. Participants generally described being able to collect treatment from pharmacies discreetly and promptly, but for some, poor awareness of the eSHC by pharmacy staff undermined their ability to do this. Those unsuitable for remote management, who were directed to clinic, described frustration and concern about health implications and clinic attendance. However, the helpline was a highly valued source of information, assistance and support., Conclusion: The eSHC is a promising adjunct to traditional care. Its users have high expectations for convenience, speed and privacy, which may be compromised when transitioning from online to face-to-face elements of the eSHC. Managing expectations and improving implementation of the pharmacy process, could improve their experiences. Positive views on the helpline provide further support for embedding this ehealth intervention within a specialist clinical service., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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 30min., 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 10days 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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

In addition to inadequate access to early diagnosis and treatment with antimicrobial agents for patients and sexual contacts, management and control of STIs is significantly challenged by emergence and spread of antimicrobial resistance (AMR), particularly for STIs such as Neisseria gonorrhoeae and Mycoplasma genitalium This is further compounded by use of nucleic acid amplification techniques for diagnosis, resulting in reduced phenotypic AMR testing for N. gonorrhoeae and absence or suboptimal AMR surveillance for guiding treatment of both STIs in many settings. Rapid accurate point-of-care (POC) tests for diagnosis of all STIs would be valuable but to significantly impact treatment precision and management of N. gonorrhoeae and M. genitalium infections, combinations of rapid POC diagnostic and AMR testing (POC-AMR) will likely be required. This strategy would combat STI burden and AMR emergence and spread by enabling diagnosis and individualised treatment at the first healthcare visit, potentially reducing selection pressure on recommended antimicrobials, reducing transmission of resistant strains and providing means for AMR surveillance. Microfluidic and nanotechnology platforms under development for rapid detection of STIs provide a basis to also develop molecular rapid POC-AMR prediction. A number of prototypic devices are in the pipeline but none as yet approved for routine use. However, particularly for N. gonorrhoeae , more knowledge is required to assess which antimicrobials lend themselves to a genotypic POC-AMR approach, in relation to genotypic-phenotypic associations and potential impact clinically and epidemiologically. Key for successful deployment will include also understanding cost-effectiveness, cost-consequences and acceptability for key stakeholders., Competing Interests: Competing interests: STS is grant holder for the National Institute for Health Research (NIHR) i4i Programme (grant number II-LB-0214-20005). The views expressed are those of the authors and not necessarily those of the NIHR, the NHS or the UK Department of Health. STS has also received funding from Atlas Genetics to conduct performance evaluations of its io POC system. None for MU and FM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Seeking sexual health information online is common, and provision of mobile medical applications (apps) for STIs is increasing. Young people, inherently at higher risk of STIs, are avid users of technology, and apps could be appealing sources of information. We undertook a comprehensive review of content and accuracy of apps for people seeking information about STIs., Methods: Search of Google Play and iTunes stores using general and specific search terms for apps regarding STIs and genital infections (except HIV), testing, diagnosis and management, 10 September 2014 to 16 September 2014. We assessed eligible apps against (1) 19 modified Health on The Net (HON) Foundation principles; and (2) comprehensiveness and accuracy of information on STIs/genital infections, and their diagnosis and management, compared with corresponding National Health Service STI information webpage content., Results: 144/6642 apps were eligible. 57 were excluded after downloading. 87 were analysed. Only 29% of apps met ≥6 HON criteria. Content was highly variable: 34/87 (39%) covered one or two infections; 40 (46%) covered multiple STIs; 5 (6%) focused on accessing STI testing. 13 (15%) were fully, 46 (53%) mostly and 28 (32%) partially accurate. 25 (29%) contained ≥1 piece of potentially harmful information. Apps available on both iOS and Android were more accurate than single-platform apps. Only one app provided fully accurate and comprehensive information on chlamydia., Conclusions: Marked variation in content, quality and accuracy of available apps combined with the nearly one-third containing potentially harmful information risks undermining potential benefits of an e-Health approach to sexual health and well-being., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Self-directed and internet-based care are key elements of eHealth agendas. We developed a complex online clinical and public health intervention, the eSexual Health Clinic (eSHC), in which patients with genital chlamydia are diagnosed and medically managed via an automated online clinical consultation, leading to antibiotic collection from a pharmacy. Partner notification, health promotion, and capture of surveillance data are integral aspects of the eSHC. We aimed to assess the safety and feasibility of the eSHC as an alternative to routine care in non-randomised, exploratory proof-of-concept studies., Methods: Participants were untreated patients with chlamydia from genitourinary medicine clinics, untreated patients with chlamydia from six areas in England in the National Chlamydia Screening Programme's (NCSP) online postal testing service, or patients without chlamydia tested in the same six NCSP areas. All participants were aged 16 years or older. The primary outcome was the proportion of patients with chlamydia who consented to the online chlamydia pathway who then received appropriate clinical management either exclusively through online treatment or via a combination of online management and face-to-face care. We captured adverse treatment outcomes., Findings: Between July 21, 2014, and March 13, 2015, 2340 people used the eSHC. Of 197 eligible patients from genitourinary medicine clinics, 161 accessed results online. Of the 116 who consented to be included in the study, 112 (97%, 95% CI 91-99) received treatment, and 74 of those were treated exclusively online. Of the 146 eligible NCSP patients, 134 accessed their results online, and 105 consented to be included. 93 (89%, 95% CI 81-94) received treatment, and 60 were treated exclusively online. In both groups, median time to collection of treatment was within 1 day of receiving their diagnosis. 1776 (89%) of 1936 NCSP patients without chlamydia accessed results online. No adverse events were recorded., Interpretation: The eSHC is safe and feasible for management of patients with chlamydia, with preliminary evidence of similar treatment outcomes to those in traditional services. This innovative model could help to address growing clinical and public health needs. A definitive trial is needed to assess the efficacy, cost-effectiveness, and public health impact of this intervention., Funding: UK Clinical Research Collaboration., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK's free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI(2) consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users., Methods: In-depth interviews were conducted in 2012 with 25 sexually-experienced 16-24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken., Results: Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test's accuracy, related to self-operation and the technology's novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals., Conclusions: Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention.

This paper presents the design of a modular point of care test platform that integrates a proprietary sample collection device directly with a microfluidic cartridge. Cell lysis, within the cartridge, is conducted using a chemical method and nucleic acid purification is done on an activated cellulose membrane. The microfluidic device incorporates passive mixing of the lysis-binding buffers and sample using a serpentine channel. Results have shown extraction efficiencies for this new membrane of 69% and 57% compared to the commercial Qiagen extraction method of 85% and 59.4% for 0.1ng/µL and 100ng/µL salmon sperm DNA respectively spiked in phosphate buffered solution. Extraction experiments using the serpentine passive mixer cartridges incorporating lysis and nucleic acid purification showed extraction efficiency around 80% of the commercial Qiagen kit. Isothermal amplification was conducted using thermophillic helicase dependant amplification and recombinase polymerase amplification. A low cost benchtop real-time isothermal amplification platform has been developed capable of running six amplifications simultaneously. Results show that the platform is capable of detecting 1.32×10(6) of sample DNA through thermophillic helicase dependant amplification and 1×10(5) copy numbers Chlamydia trachomatis genomic DNA within 10min through recombinase polymerase nucleic acid amplification tests., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England., Methods: Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway)., Results: Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation., Conclusion: The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.

Background: The annual number of new human immunodeficiency virus (HIV) infections in the United Kingdom among men who have sex with men (MSM) has risen, and remains high among heterosexuals. Increasing HIV transmission among MSM is consistent with evidence of ongoing sexual risk behavior in this group, and targeted prevention strategies are needed for those at risk of acquiring HIV., Objective: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study was designed to collect information on HIV negative adults at risk of HIV infection in the United Kingdom, based on the following parameters: physical and mental health, lifestyle, patterns of sexual behaviour, and attitudes to sexual risk., Methods: Cross-sectional questionnaire study of HIV negative or undiagnosed sexual health clinic attendees in the United Kingdom from 2013-2014., Results: Of 2630 participants in the AURAH study, 2064 (78%) were in the key subgroups of interest; 580 were black Africans (325 females and 255 males) and 1484 were MSM, with 27 participants belonging to both categories., Conclusions: The results from AURAH will be a significant resource to understand the attitudes and sexual behaviour of those at risk of acquiring HIV within the United Kingdom. AURAH will inform future prevention efforts and targeted health promotion initiatives in the HIV negative population.

Introduction: Increasing use of nucleic acid amplification tests (NAATs) as the primary means of diagnosing gonococcal infection has resulted in diminished availability of Neisseria gonorrhoeae antimicrobial susceptibility data. We conducted a prospective diagnostic assessment of a real-time PCR assay (NGSNP) enabling direct detection of gonococcal ciprofloxacin susceptibility from a range of clinical sample types., Methods: NGSNP, designed to discriminate an SNP associated with ciprofloxacin resistance within the N. gonorrhoeae genome, was validated using a characterized panel of geographically diverse isolates (n = 90) and evaluated to predict ciprofloxacin susceptibility directly on N. gonorrhoeae-positive NAAT lysates derived from genital (n = 174) and non-genital (n = 116) samples (n = 290), from 222 culture-confirmed clinical episodes of gonococcal infection., Results: NGSNP correctly genotyped all phenotypically susceptible (n = 49) and resistant (n = 41) panel isolates. Ciprofloxacin-resistant N. gonorrhoeae was responsible for infection in 29.7% (n = 66) of clinical episodes evaluated. Compared with phenotypic susceptibility testing, NGSNP demonstrated sensitivity and specificity of 95.8% (95% CI 91.5%-98.3%) and 100% (95% CI 94.7%-100%), respectively, for detecting ciprofloxacin-susceptible N. gonorrhoeae, with a positive predictive value of 100% (95% CI 97.7%-100%). Applied to urogenital (n = 164), rectal (n = 40) and pharyngeal samples alone (n = 30), positive predictive values were 100% (95% CI 96.8%-100%), 100% (95% CI 87.2%-100%) and 100% (95% CI 82.4%-100%), respectively., Conclusions: Genotypic prediction of N. gonorrhoeae ciprofloxacin susceptibility directly from clinical samples was highly accurate and, in the absence of culture, will facilitate use of tailored therapy for gonococcal infection, sparing use of current empirical treatment regimens and enhancing acquisition of susceptibility data for surveillance., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Advances in microfluidics and the introduction of isothermal nucleic acid amplification assays have resulted in a range of solutions for nucleic acid amplification tests suited for point of care and field use. However, miniaturisation of instrumentation for such assays has not seen such rapid advances and fluorescence based assays still depend on complex, bulky and expensive optics such as fluorescence microscopes, photomultiplier tubes and sensitive lens assemblies. In this work we demonstrate a robust, low cost platform for isothermal nucleic acid amplification on a microfluidic device. Using easily obtainable materials and commercial off-the-shelf components, we show real time fluorescence detection using a low cost photodiode and operational amplifier without need for lenses. Temperature regulation on the device is achieved using a heater fabricated with standard printed circuit board fabrication methods. These facile construction methods allow fabrications at a cost compatible with widespread deployment to resource poor settings.

Background: The increasing pervasiveness of mobile technologies has given potential to transform healthcare by facilitating clinical management using software applications. These technologies may provide valuable tools in sexual health care and potentially overcome existing practical and cultural barriers to routine testing for sexually transmitted infections. In order to inform the design of a mobile health application for STIs that supports self-testing and self-management by linking diagnosis with online care pathways, we aimed to identify the dimensions and range of preferences for user interface design features among young people., Methods: Nine focus group discussions were conducted (n = 49) with two age-stratified samples (16 to 18 and 19 to 24 year olds) of young people from Further Education colleges and Higher Education establishments. Discussions explored young people's views with regard to: the software interface; the presentation of information; and the ordering of interaction steps. Discussions were audio recorded and transcribed verbatim. Interview transcripts were analysed using thematic analysis., Results: Four over-arching themes emerged: privacy and security; credibility; user journey support; and the task-technology-context fit. From these themes, 20 user interface design recommendations for mobile health applications are proposed. For participants, although privacy was a major concern, security was not perceived as a major potential barrier as participants were generally unaware of potential security threats and inherently trusted new technology. Customisation also emerged as a key design preference to increase attractiveness and acceptability., Conclusions: Considerable effort should be focused on designing healthcare applications from the patient's perspective to maximise acceptability. The design recommendations proposed in this paper provide a valuable point of reference for the health design community to inform development of mobile-based health interventions for the diagnosis and treatment of a number of other conditions for this target group, while stimulating conversation across multidisciplinary communities.

In this paper we outline the current data capture systems for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) surveillance used by Public Health England (PHE), and how these will be affected by the introduction of novel testing platforms and changing patient pathways. We outline the Chlamydia Online Clinical Care Pathway (COCCP), developed as part of the Electronic Self-Testing for Sexually Transmitted Infections ( e STI 2 ) Consortium, which ensures that surveillance data continue to be routinely collected and transmitted to PHE. We conclude that both novel diagnostic testing platforms and established data capture systems must be adaptable to ensure continued robust public health surveillance.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum., Patients and Methods: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929., Results: Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported., Conclusions: Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir., Methods: This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women treated with boosted atazanavir (300/100 mg or 400/100 mg atazanavir/ritonavir) as part of their combination antiretroviral therapy (cART) were included in the study. 24 h pharmacokinetic curves were recorded in the third trimester and postpartum. Collection of a cord blood and maternal sample at delivery was optional., Results: 31 patients were included in the analysis, 21/31 patients used tenofovir as part of cART. Median (range) gestational age at delivery was 39 weeks (36-42). Approaching delivery 81% (25 patients) had an HIV viral load <50 copies/ml, all <1,000 copies/ml. Least squares means ratios (90% CI) of atazanavir pharmacokinetic parameters third trimester/postpartum were: 0.66 (0.57, 0.75) for AUC0-24h, 0.70 (0.61, 0.80) for Cmax and 0.59 (0.48, 0.72) for C24h. No statistical difference in pharmacokinetic parameters was found between patients using tenofovir versus no tenofovir. None of the patients showed atazanavir concentrations <0.15 mg/l (target for treatment-naive patients). One baby had a congenital abnormality, which was not likely to be related to atazanavir/ritonavir use. None of the children were HIV-infected., Conclusions: Despite 34% lower atazanavir exposure during pregnancy, atazanavir/ritonavir 300/100 mg once daily generates effective concentrations for protease inhibitor (PI)-naive patients, even if co-administered with tenofovir. For treatment-experienced patients (with relevant PI resistance mutations) therapeutic drug monitoring of atazanavir should be considered to adapt the atazanavir/ritonavir dose on an individual basis.
 ClinicalTrials.gov number NCT00825929.

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.

Thousands of bacterial phylotypes colonise the human body and the host response to this bacterial challenge greatly influences our state of health or disease. The concept of infectogenomics highlights the importance of host genetic factors in determining the composition of human microbial biofilms and the response to this microbial challenge. We hereby introduce the term 'genetic dysbiosis' to highlight the role of human genetic variants affecting microbial recognition and host response in creating an environment conducive to changes in the normal microbiota. Such changes can, in turn, predispose to, and influence, diseases such as: cancer, inflammatory bowel disease, rheumatoid arthritis, psoriasis, bacterial vaginosis and periodontitis. This review presents the state of the evidence on host genetic factors affecting dysbiosis and microbial misrecognition (i.e. an aberrant response to the normal microbiota) and highlights the need for further research in this area.

Implementing clinical audit in a resource poor setting is often beset by practical issues. Out-sourcing the burden of data analysis may go a long way to facilitating regular audit in a resource poor setting. We investigated the feasibility of using an inexpensive 12-megapixel point-and-shoot digital camera to collect data from clinical notes in a format capable of being sent via secure electronic file transfer for remote analysis. We then performed a pilot audit on this data as a proof of principle.

Objectives: Environmental contamination with DNA from Chlamydia trachomatis (CT) has previously been found in Genitourinary Medicine (GUM) clinics. There are no known cases of cross-contamination of clinical samples and no known nosocomial infections. We investigated whether diagnostic samples could become contaminated from the environment by running dummy sample and carrying out a patient-throughput analysis. A total of 29 748 patients attended clinics over a year. Of these, 2860 (9.6%) had a positive Chlamydia test result., Method: (1) A run of dummy samples (60 urine samples and 10 swabs) were processed as normal clinic specimens. (2) Patient-throughput analysis: Patient numbers attending the GUM clinic on a given day was categorised as low, moderate or high. χ(2) Tests were used to look for associations between categorical variables and Chlamydia test positivity. A Poisson regression model was fitted to look at the effect of the number of people in the clinic on the number of positive results in a given day. As some clinics were only run on certain days of the week, a sensitivity analysis was later performed with attendances at non-daily clinics removed., Results: All dummy samples tested negative and we did not find evidence of an association between daily Chlamydia positivity and clinic attendance., Conclusions: It is unlikely that environmental or cross-contamination of CT has lead to significant numbers of false positive results. Laboratories check for possible cross-contamination routinely. The extension of this simple routine practice to all clinical areas could provide quality assurance, improving confidence in the results in clinics.

Objective: To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls., Design: Cohort study, Setting: 20 London universities and further education colleges., Participants: 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV., Results: Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, aged<20, of black ethnicity, or with C trachomatis vaginosis at baseline. Multiple partners was the only independent risk factor for incident infection (adjusted relative risk 1.99 (95% CI 1.46 to 2.72)). Of 143 women with baseline carcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes., Conclusion: In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV types, immunised women will still need cervical screening.

Objectives: To determine differences in CYP2B6 loss of function (LoF) single nucleotide polymorphisms (SNPs) and haplotypes between Zimbabweans and Ugandans, and within Ugandan populations (Bantu and Nilotic)., Methods: Genetic epidemiological study enrolling adult black African Ugandan and Zimbabwean patients attending a UK HIV-1 clinic, irrespective of antiretroviral therapy status. Genomic DNA was extracted from whole blood and the presence of CYP2B6 alleles was determined by direct sequencing of all nine exons of the CYP2B6 gene. Blood was also collected, where appropriate, for determination of efavirenz concentrations. Frequency of SNPs in all patients and LoF haplotype frequencies were calculated. The relationship between the number of LoF haplotype alleles possessed and efavirenz trough concentration (ETC) was determined., Results: Thirty-six Zimbabweans and 74 Ugandans (58 Bantu and 16 Nilotic) were recruited. The definite haplotypes determined were *6, *18, *20 and *27 as LoF and *4 as gain of function. Among those with definite genotypes, the frequency of LoF alleles was 65% [95% confidence interval (95% CI): 51-80] of Zimbabweans versus 22% (95% CI: 12-31) of Ugandan Bantus (P = 10(-6)) and versus 39% (95% CI: 14-64) of Ugandan Nilotics (P = 0.09). Among the 19 patients with definite genotype and with available ETCs, log ETCs were associated with a greater number of LoF haplotype alleles [848 ng/mL (n = 12), 1069 ng/mL (n = 4) and 1813 ng/mL (n = 3) for 0, 1 or 2 LoF haplotypes, respectively (P = 0.016)]., Conclusions: Among Zimbabweans, LoF haplotypes constitute the majority of CYP2B6 alleles and are significantly higher in prevalence compared with Ugandans. Frequencies of LoF haplotypes and SNPs in Ugandan Nilotics appear to lie between those of Zimbabweans and Ugandan Bantus. These findings may have relevance to pharmacokinetics and dosing of efavirenz in African populations.

Objectives: Performance of the new Becton Dickinson ProbeTec GC Q(x) assay on the BD VIPER platform was evaluated to ascertain whether confirmatory testing is required in our clinical setting., Methods: Positive predictive value (PPV) was determined by comparison with culture and a confirmatory nucleic acid amplification test (NAAT)-based Neisseria gonorrhoeae assay from genital and extragenital samples (rectal and pharyngeal) collected from a genitourinary medicine (GUM) clinic., Results: Among 14,223 clinical genital samples, 149 (1.0%) specimens were positive using the ProbeTec GC Q(x) assay, automated on the VIPER platform; 141 of these were confirmed by either culture or a real-time PCR targeting two gonococcal-specific targets (PPV 94.6%; 95% CI 90% to 98%). Among 840 pharyngeal samples, 26 (3.1%) were positive by the ProbeTec GC Q(x) assay; 13 were confirmed (PPV 50%; 95% CI 30% to 70%). Among 593 rectal samples, 17 tested positive by the ProbeTec GC Q(x) assay; all were confirmed (PPV 100%; 95% CI 80% to 100%)., Conclusions: The lower 95% CI of the PPV for the ProbeTec GC Q(x) assay for genital specimens was >90% in this GUM clinic population, and therefore confirmatory testing for genital specimens is not required. Confirmatory testing of pharyngeal and rectal samples should continue in line with national guidelines.

Background: To determine patient and treatment characteristics associated with vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort., Methods: Two hundred twenty-seven HIV-positive patients attending prospectively for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations and other routine chemistry measured. Those with and without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50 nmol/L and >75 nmol/L, respectively. Characteristics were compared between patients with and without VDD. The effects of VDD, tenofovir use, and their interaction on chemical measures were investigated., Results: VDD was found in 57% (131 of 227) of patients. Independent associations included nonwhite ethnicity [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19 (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L) than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir occurred only in the context of VDD. Tenofovir use was not associated with serum creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P = 0.08, respectively), being linked to somewhat higher creatinine and lower eGFR among patients without VDD but higher eGFR in VDD patients., Conclusions: 25(OH) VDD is associated with tenofovir-linked hyperparathyroidism and also with higher eGFR.

Objectives: To assess the impact of computer-assisted interview compared with pen and paper on disclosure of sexual behaviour, diagnostic testing by clinicians, infections diagnosed and referral for counselling., Methods: Two-centre parallel three-arm randomised controlled open trial. Computer-generated randomisation with allocation concealment using sealed envelopes., Setting: Two London teaching hospital sexual health clinics., Participants: 2351 clinic attenders over the age of 16 years., Interventions: Computer-assisted self-interview (CASI). Computer-assisted personal interview (CAPI). Pen and paper interview (PAPI)., Main Outcome Measures: Diagnostic tests ordered, sexually transmitted infections (STI)., Secondary Outcomes: Disclosure of sexual risk, referral for counselling., Results: 801, 763 and 787 patients randomly allocated to receive CASI, CAPI and PAPI. 795, 744 and 779 were available for intention-to-treat analysis. Significantly more diagnostic testing for hepatitis B and C and rectal samples in the CAPI arm (odds for more testing relative to PAPI 1.32; 95% CI 1.09 to 1.59). This pattern was not seen among CASI patients. HIV testing was significantly lower among CASI patients (odds for less testing relative to PAPI 0.73; 95% CI 0.59 to 0.90). STI diagnoses were not significantly different by trial arm. A summary measure of seven prespecified sensitive behaviours found greater reporting with CASI (OR 1.4; 95% CI 1.2 to 1.6) and CAPI (OR 1.4; 95% CI 1.2 to 1.7) compared with PAPI., Conclusion: CASI and CAPI can generate greater recording of risky behaviour than traditional PAPI. Increased disclosure did not increase STI diagnoses. Safeguards may be needed to ensure that clinicians are prompted to act upon disclosures made during self-interview.

Background: High throughput proteomic technology offers promise for the detection of disease biomarkers and proteomic signature patterns but biomarker discovery studies can be limited by cost factors when large sample size numbers are required. Pooling sera or plasma samples from disease cases potentially offers a solution to cost implications by reducing the standard errors of mass to charge values. Surface enhanced laser desorption/ionization time of flight (SELDI-ToF) mass spectra obtained from individual and pooled sera from invasive aspergillosis cases and controls were compared., Results: Pooling resulted in 50% loss of peak clusters detected in individual samples. Overall, loss was greatest for low intensity clusters. Peak intensities and case:control intensity ratios, among clusters not lost, demonstrated good reproducibility., Conclusion: Pooling sera results in significant potential biomarker loss when using SELDI-ToF MS.

Objective: To identify opportunities for earlier HIV diagnosis within primary and secondary care settings in the UK in Africans with newly diagnosed HIV infection., Methods: A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was conducted between April 2004 and February 2006. The survey consisted of a confidential self-completed questionnaire linked to clinician-completed clinical records., Results: A total of 263 questionnaires were completed, representing an uptake rate of 79.5% of patients approached and 49.8% (131/263) of participants presented with advanced HIV disease (CD4 cell count < 200 cells/mul at diagnosis). In the year prior to HIV diagnosis 76.4% (181/237) had seen their GP, 38.3% (98/256) had attended outpatient services, and 15.2% (39/257) inpatient services, representing missed opportunities for earlier HIV diagnosis. Of those attending GP services the issue of HIV and/or HIV testing was raised for 17.6% (31/176) and 37.1% (78/210) had a previous negative HIV test, 32.5% of these within the UK. Medical attention was sought for wide ranging reasons, often not obviously connected to underlying HIV status. Despite the population predominantly coming from countries of high HIV prevalence personal appreciation of risk was comparatively low and knowledge of benefits of testing lacking., Conclusion: Africans are accessing health services but clinicians are failing to use these opportunities effectively for preventive and diagnostic purposes with regards to HIV infection. Comparatively low appreciation of personal risk and lack of perceived ill health within this community means clinicians need to be more proactive in addressing HIV.

Objective: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts., Methods: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20)., Results: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either., Conclusions: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen.

Objectives: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting., Methods: Prospective case-control study. HIV-1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV-1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks., Results: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU., Conclusions: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world.

Background/objectives: The criteria for the diagnosis of non-gonococcal urethritis (NGU) on a Gram stained urethral smear are derived from previous studies which used culture as a diagnostic test for Chlamydia trachomatis. Our objectives were (1). to re-assess the relation between urethral polymorph count and C trachomatis infection, using ligase chain reaction (LCR) as the diagnostic test; and (2). to assess other possible predictors of C trachomatis infection such as symptoms, signs, demographic and behavioural variables., Methods: We collected data from 363 men consecutively attending a genitourinary medicine clinic (excluding those with gonorrhoea and follow up visits) who had a urethral smear and a urethral LCR test for C trachomatis. The sensitivity and specificity of a discrete cut off in urethral polymorphonuclear leucocyte (PMNL) count as a diagnostic test for chlamydia urethritis were calculated. The associations between other variables, such as age and symptoms, and this infection were also estimated., Results: 8% of men had C trachomatis infection and 26% of men had a PMNL count of 5 or more. Of those men with chlamydia 37% did not have NGU; 20% of men with NGU had chlamydia. Adjusted odds ratios for risk of chlamydial infection were significant for age less than 30 relative to 40 years and over (adj OR 13.6; 95% confidence interval 1.69 to 110), a PMNL count of 20 or more (6.56; 2.15 to 20.0), a PMNL count of 5-19 (3.59; 1.41 to 9.15), and the symptom of dysuria (3.27; 1.32 to 8.08). However a PMNL count of 5 or more was only 63% sensitive and 77% specific for C trachomatis infection. No association between sexual behaviour and chlamydial infection was found in this setting., Conclusions: The PMNL count is associated with presence of chlamydial infection but a large proportion of men with chlamydia have PMNL counts below the recommended cut off for a diagnosis of NSU. Lower age and the presence of symptoms may be as predictive as the urethral polymorph count for chlamydial urethritis and possibly for other urethral infections.

Objectives: To determine the reliability of the diagnosis of non-gonococcal urethritis (NGU), and the variation between and within microscopists, from urethral smears at a large London genitourinary medicine clinic., Methods: A senior microscopist (SM) preselected 60 Gram stained urethral smear slides, 20 negative (<5 polymorphs/hpf), 20 low grade NGU (5-20 p/hpf), and 20 high grade NGU (>20 p/hpf). Ten experienced microscopists, blinded to these initial grades, examined all slides giving each a polymorph score. After relabelling and randomly changing their order, the slides were re-examined by the same microscopists. Finally, the SM determined whether the study had resulted in loss of cells from any of the slides. The SM's initial grading and the consensus among microscopists provide two gold standards for analysis., Results: Nine low grade and five high grade slides were removed from analysis because of loss of cells. By SM standard, considering microscopists' readings as simply non-NGU (<5 p/hpf) or NGU (>or=5 p/hpf), 97% from negative slides were correct (variation 93-100 across microscopists), 68% from low grade slides (45-95), and 94% from high grade slides (83-100). Consistency between repeat readings by the same microscopist was 96% for negatives, 75% for low grade and 89% for high grade slides. Results were similar by consensus standard., Conclusions: There was considerable variation between and within microscopists in the diagnosis of NGU. Sensitivity was strongly related to grade of urethritis, with an appreciable proportion of low grade urethritis falsely diagnosed as negative. With increasing attendances for sexual health screening, a false positive rate of only 3% may lead to many false diagnoses.

Sexually transmitted infections may enhance the sexual transmission of HIV-1. It is possible that loss of virological control in patients with such infections receiving antiretroviral therapy (ART) may even facilitate the transmission of drug-resistant HIV. We have recently demonstrated that in those on maximally suppressive ART this effect is reduced. We have examined the virus obtained from the blood plasma and seminal plasma of six HIV-1-infected men receiving poorly suppressive ART with acute urethritis for the presence of drug resistance-associated mutations. In four men with gonorrhoea the blood and seminal plasma HIV-1 had mutations conferring reduced susceptibility to one or more available drugs. In one of these men the viral load of drug-resistant virus in seminal plasma was 20-fold higher during gonorrhoea than following antibiotic treatment, with no change in blood plasma viral load. We conclude that in the presence of suboptimal ART, sexually transmitted infections may enhance the spread of drug-resistant HIV-1.

Two HIV infected patients presented with peripheral neuropathy, in one patient this was originally ascribed to HIV associated mononeuritis multiplex and in the other to stavudine. Investigations confirmed these diagnoses and in both cases genetic analysis identified a second hereditary aetiology: in the first patient hereditary neuropathy with liability to pressure palsies and in the second hereditary motor and sensory neuropathy.