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Patients diagnosed with lymphogranuloma venereum have high rates of co-infection with HIV, syphilis and hepatitis C. The aim of this enhanced surveillance was to screen all men who have sex with men (MSM) newly diagnosed with HIV, syphilis or hepatitis C for co-infection with asymptomatic lymphogranuloma venereum as part of the recommended sexual health screen. Of the 145 patients screened, 21 patients were diagnosed with rectal Chlamydia trachomatis, one with both rectal and urethral chlamydia and six with urethral chlamydia. One rectal chlamydia-positive sample, when tested, was equivocal for lymphogranuloma venereum. Our data suggested that there was not a pool of asymptomatic lymphogranuloma venereum infection in MSM recently diagnosed with HIV, hepatitis C and syphilis. However, there have been recent reports of an increased incidence of asymptomatic lymphogranuloma venereum, raising the question whether lymphogranuloma venereum should be screened for in high risk asymptomatic MSM. The prevalence of asymptomatic rectal chlamydia infections was 19%., (© The Author(s) 2015.)

These guidelines are an update for 2015 of the 2008 UK guidelines for the management of syphilis. The writing group have piloted the new BASHH guideline methodology, notably using the GRADE system for assessing evidence and making recommendations. We have made significant changes to the recommendations for screening infants born to mothers with positive syphilis serology and to facilitate accurate and timely communication between the teams caring for mother and baby we have developed a birth plan. Procaine penicillin is now an alternative, not preferred treatment, for all stages of syphilis except neurosyphilis, but the length of treatment for this is shortened. Other changes are summarised at the start of the guideline., (© The Author(s) 2016.)

Background: Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data., Methods: The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD)., Results: The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees., Conclusions: The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective., Trial Registration: Current Controlled Trials ISRCTN94465371 . Date of registration: 28 February 2013.

Objectives: To assess the extent of nondisclosure of known HIV status among sexual health clinic attendees and to quantify the impact of nondisclosure on estimates of undiagnosed HIV prevalence and of the proportion of patients remaining undiagnosed on leaving the clinic., Methods: Serum samples from the unlinked anonymous survey of clinic attendees' archive were tested for antiretrovirals. Estimates of undiagnosed HIV were adjusted using the findings., Results: Antiretrovirals were detected in 27% of samples taken from 'previously undiagnosed' attendees, who did not have an HIV test but were HIV positive as detected by unlinked anonymous testing, indicating nondisclosure; 24% of such samples from MSM had antiretrovirals present compared with 32% of heterosexual men and women. Antiretrovirals were detected in 33% of samples from London clinics and in 21% from non-London clinics. Following adjustment, the estimated prevalence of undiagnosed HIV decreased nonsignificantly from 3.04% (95% confidence interval 2.71-3.41) to 2.66% (2.35-3.01) among men who have sex with men (MSM), 0.31% (0.26-0.37) to 0.30% (0.25-0.36) in heterosexual men and 0.40% (0.35-0.46) to 0.37% (0.32-0.43) in women; 7% of MSM who do not have an HIV test at a clinic visit will be infected with HIV and remain unaware of their infection., Conclusion: Nondisclosure of HIV status to healthcare professionals occurs among clinic attendees. Adjustment for nondisclosure results in a small, nonsignificant decrease in the prevalence of undiagnosed HIV estimated from the unlinked anonymous survey in sexual health clinics. Testing the population of MSM not having an HIV test remains a priority as levels of undiagnosed HIV are high.

Background: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect., Methods: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986)., Findings: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients., Interpretation: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection., Funding: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences., (Copyright © 2016 McCormack et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Objective: To identify risk factors for rectal lymphogranuloma venereum (rLGV) in men who have sex with men (MSM)., Design: A case-control study at 6 U.K. hospitals compared MSM with rLGV (cases) with rLGV-negative controls: MSM without potential rLGV symptoms (CGa) and separately, MSM with such symptoms (CGs)., Methods: Between 2008 and 2010, there were 90 rLGV cases, 74 CGa and 69 CGs recruited. Lifestyles and sexual behaviours in the previous 3 months were reported using internet-based computer-assisted self-interviews. Logistic regression was used to investigate factors associated with rLGV., Results: Cases were significantly more likely to be HIV-positive (89%) compared with CGa (46%) and CGs (64%). Independent behavioural risks for rLGV were: unprotected receptive anal intercourse (adjusted OR (AOR)10.7, 95% CI 3.5 to 32.8), fisting another (AOR=6.7, CI 1.8 to 25.3), sex under the influence of gamma-hydroxybutyrate (AOR=3.1, CI 1.3 to 7.4) and anonymous sexual contacts (AOR=2.7, CI 1.2 to 6.3), compared with CGa; unprotected insertive anal intercourse (AOR=4.7, CI 2.0 to 10.9) and rectal douching (AOR=2.9 CI 1.3 to 6.6), compared with CGs. An incubation period from exposure to symptoms of 30 days was indicated., Conclusions: Unprotected receptive anal intercourse is a key risk factor for rectal LGV with the likelihood that rectal-to-rectal transmission is facilitated where insertive anal sex also occurs. The association between HIV and rLGV appears linked to HIV-positive men seeking unprotected sex with others with the same HIV status, sexual and drug interests. Such men should be targeted for frequent STI screening and interventions to minimise associated risks., (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.)

Background: National guidance recommends targeted behavioural interventions and frequent HIV testing for men who have sex with men (MSM). We reviewed current policy and practice for HIV testing and behavioural interventions (BI) in England to determine adherence to guidance., Methods: 25 sexual health clinics were surveyed using a semistructured audit asking about risk ascertainment for MSM, HIV testing and behavioural intervention policies. Practice was assessed by reviewing the notes of the first 40 HIV-negative MSM aged over 16 who attended from 1 June 2010, in a subset of 15 clinics., Results: 24 clinics completed the survey: 18 (75%) defined risk for MSM and 17 used unprotected anal intercourse (UAI) as an indication of high risk. 21 (88%) offered one or more structured BI. Of 598 notes reviewed, 199 (33%) MSM reported any UAI. BI, including safer sex advice, was offered to and accepted by 251/598 (42%) men. A low proportion of all MSM (52/251: 21%) accepted a structured one-to-one BI as recommended by national guidance and uptake was still low among higher risk MSM (29/107: 27%). 92% (552/598) of men had one or more HIV test over a 1-year period., Conclusions: In 2010, the number of HIV tests performed met the national minimum standard but structured behavioural interventions were being offered to and accepted by only a small proportion of MSM, including those at a higher risk of infection. Reasons for not offering behavioural interventions to higher risk MSM, whether due to patient choice, a lack of staff training or resource shortage, need to be investigated and addressed.

Objectives: To identify if HIV-infected individuals attending genitourinary clinics in the UK are not disclosing their HIV status, and to examine the potential utility of drug detection as a method to indicate non-disclosure., Methods: HIV-positive samples from the unlinked anonymous seroprevalence survey from one London centre in 2009 had viral load (VL) assays performed to identify samples with VL below the level of detection (50 copies/ml, VLBLD) or <1000 copies/ml. After data matching, known HIV positives were excluded and the remaining samples analysed for the presence of a panel of antiretroviral drugs., Results: Of 130 HIV-positive samples with sufficient clinical information and not undergoing an HIV test, 18 were classified as remaining undiagnosed after the clinic visit. Thirteen (72%, 95% CI: 47% to 90%) had a VLBLD (n=11) or VL <1000 copies/ml (n=2). Eight had sufficient volume to undergo ARV testing, and all were positive for the presence of drug; all with therapeutic levels of clinically appropriate combinations., Conclusions: Non-disclosure of HIV status occurs among individuals attending sexual health services in the UK. This study demonstrates the feasibility and utility of using both VL and ARV assays in serum samples. Furthermore, the close correlation of detection of ARV with VLBLD suggests drug detection would be a useful tool to monitor non-disclosure prospectively, thus enabling the use of stored serum samples in future studies. The extent to which these findings can be extrapolated to other settings, and the potential impact of non-disclosure on undiagnosed estimates warrants urgent prospective study.

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.

Objectives: To explore staff attitudes towards and experiences of the implementation of routine HIV testing in four healthcare settings in areas of high diagnosed HIV prevalence., Methods: As part of the HINTS (HIV Testing in Non-traditional Settings) Study, routine offer of an HIV test to all 16-65-year-old patients was conducted for 3 months in an emergency department, an acute admissions unit, a dermatology outpatients department and a primary care practice. The authors conducted focus groups with staff at these sites before and after the implementation of testing. Transcriptions of focus groups were subject to thematic analysis., Results: Four major themes were identified: the stigma of HIV and exceptionalisation of HIV testing as a condition; the use of routine testing compared with a targeted strategy as a means of improving the acceptability of testing; the need for an additional skill set to conduct HIV testing; and the existence within these particular settings of operational barriers to the implementation of HIV testing. Specifically, the time taken to conduct testing and management of results were seen by staff as barriers. There was a clear change in staff perception before and after implementation of testing as staff became aware of the high level of patient acceptability., Conclusions: The routine offer of HIV testing in general medical services is feasible, but implementation requires training and support for staff, which may be best provided by the local sexual health service.

This paper reports on chlamydial partner notification (PN) performance in the 2011 BASHH national audit against the British Association for Sexual Health and HIV (BASHH) Medical Foundation for AIDS Sexual Health (MedFASH) Sexually Transmitted Infection Management Standards (STIMS). There was wide regional variation in level 3 clinic PN performance against the current standard of index case-reported chlamydial PN, with 43% (regional range 0-80%) of clinics outside London meeting the ≥0.6 contacts seen per index standard, and 85% of clinics (regional range 82-88%) in London meeting the ≥0.4 standard. For level 2 clinics, 39% (regional range 0-100%) of clinics outside London met the ≥0.6 standard, and 43% (regional range 40-50%) of clinics in London met the ≥0.4 standard. Performance for health-care worker (HCW)-verified contact attendance is also reported. New standards for each of these performance measures are proposed for all level 3 clinics: ≥0.6 contacts seen per index case based on index case report, and ≥0.4 contacts seen per index case based on HCW verification, both within four weeks of the first partner notification interview. The results are discussed with regard to the importance of adoption of standards by commissioners of services, relevance to national quality agendas, and the need for development of a national system of PN quality assurance measurement and reporting.

A national audit of practice performance against the key performance indicators in the British Association for Sexual Health and HIV (BASHH) and HIV Medical Foundation for AIDS Sexual Health Standards for the Management of Sexually Transmitted Infections (STIs) was conducted in 2011. Approximately 60% and 8% of level 3 and level 2 services, respectively, participated. Excluding partner notification performance, the five lowest areas of performance for level 3 clinics were the STI/HIV risk assessment, care pathways linking care in level 2 clinics to local level 3 services, HIV test offer to patients with concern about STIs, information governance and receipt of chlamydial test results by clinicians within seven working days (the worst area of performance). The five lowest areas of performance for level 2 clinics were participating in audit, having an audit plan for the management of STIs for 2009-2010, the STI/HIV risk assessment, HIV test offer to patients with concern about STIs and information governance. The results are discussed with regard to the importance of adoption of the standards by commissioners of services because of their relevance to other national quality assurance drivers, and the need for development of a national system of STI management quality assurance measurement and reporting.

Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4(+) T cells from chagasic patients preferentially express T cell receptor (TCR) β-chain variable region (Vβ) 5. The aim of this work was to determine whether T cells expressing this particular Vβ region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vβ5·1 expressing CD4(+) T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jβ region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4(+)Vβ5·1(+) cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy., (© 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.)

This guideline provides evidence-based guidance on the content of safer sex advice and the provision of brief behaviour change interventions deliverable in genitourinary (GU) medicine clinics. Much of the advice is applicable to other healthcare settings including general practice and clinics providing HIV care. Advice on condom use and effectiveness, oral sex and other sexual practices, testing for sexually transmitted infections (STI) and partner reduction is provided. Advice specific to the transmission of HIV infection including seroadaptive behaviours and negotiated safety is also included. An accompanying review of the evidence supporting the guideline with a complete reference list is available online. A patient information leaflet based on the advice statements developed is also available through the BASHH website.

A focused repeat national audit of sexual history-taking was conducted in genitourinary (GU) medicine clinics in the UK in 2010, addressing several areas of practice under-performance identified in the baseline 2008 national audit. The case-notes of 4285 patients were audited. An increase in documentation was observed for all measures, except legibility which was unchanged. Despite the overall improvement, several measures (chaperone offer, condom usage and four of five aspects of HIV risk assessment) remained below target.

Background: UK guidelines recommend routine HIV testing in healthcare settings if the local diagnosed HIV prevalence >2/1000 persons. This prospective study assessed the feasibility and acceptability, to patients and staff, of routinely offering HIV tests in four settings: Emergency Department, Acute Care Unit, Dermatology Outpatients and Primary Care. Modelling suggested the estimated prevalence of undiagnosed HIV infection in attendees would exceed 1/1000 persons. The prevalence identified prospectively was not a primary outcome., Methods: Permanent staff completed questionnaires assessing attitudes towards routine HIV testing in their workplace before testing began. Subsequently, over a three-month period, patients aged 16-65 were offered an HIV test by study staff. Demographics, uptake, results, and departmental activity were collected. Subsets of patients completed questionnaires. Analyses were conducted to identify factors associated with test uptake., Findings: Questionnaires were received from 144 staff. 96% supported the expansion of HIV testing, but only 54% stated that they would feel comfortable delivering testing themselves, with 72% identifying a need for training. Of 6194 patients offered a test, 4105 (66·8%) accepted (61·8-75·4% across sites). Eight individuals were diagnosed with HIV (0-10/1000 across sites) and all transferred to care. Younger people, and males, were more likely to accept an HIV test. No significant associations were found between uptake and ethnicity, or clinical site. Questionnaires were returned from 1003 patients. The offer of an HIV test was acceptable to 92%. Of respondents, individuals who had never tested for HIV before were more likely to accept a test, but no association was found between test uptake and sexual orientation., Conclusions: HIV testing in these settings is acceptable, and operationally feasible. The strategy successfully identified, and transferred to care, HIV-positive individuals. However, if HIV testing is to be included as a routine part of patients' care, additional staff training and infrastructural resources will be required.

Background: Increasing access to sexual health services is a key objective for the Department of Health in England and Wales. In 2006 it published 10 high-impact changes (HICs) designed to enhance 48 h access to genitourinary medicine services. However, there is limited evidence on the effectiveness of the proposed interventions., Objective: To evaluate the implementation of five HICs in three sexual health clinics over 4 years. These HICs included a text message results service, nurse-delivered asymptomatic service, clinic refurbishment, a centralised booking service and an electronic appointment system., Methods: The effect of HICs was evaluated by measuring clinical activity, number of sexual health screens performed, and patients seen within 48 h. These data were obtained from the clinic database, mandatory reports and Health Protection Agency waiting time surveys, respectively., Results: The median number of new patients seen per month increased from 3635 to 4263 following the implementation of the five HICs. The follow-up/new patient ratio fell from 0.67 to 0.21 during the study. The biggest fall corresponded to a rise in patients receiving results by text message, from 0% to 40%. Only the centralised booking service was associated with a significant increase in the number of new patients seen., Discussion: Providing results by text message was associated with a reduced number of follow-up patients, while implementation of a centralised booking service coincided with a significant increase in patient access. Further research is required to evaluate the relative importance of the other HICs.

Of clinics responding to the audit, 99 and 97% have policies that are compliant with the British Association for Sexual Health and HIV National Guidelines for testing of asymptomatic men and women for HIV and syphilis, respectively. All clinics offer men, and all but one clinic offer women, screening for chlamydial infection with nucleic acid amplification tests (NAATs), as recommended by the guidelines. However, for gonorrhoea screening one-third of clinics offer men urine or urethral NAATs, and one quarter of clinics offer women endocervical, vulvovaginal or urinary NAATs, and not endocervical culture, and these practices are not compliant with the guidelines. Eight clinics did not specify whether they routinely offer testing for gonorrhoea in women. One-third of clinics routinely perform rectal and oropharyngeal screening for gonorrhoea in men who have sex with men (MSM), but fewer screen for chlamydia, regardless of sexual history which is stated as a determinant of offering screening at these anatomical sites. Finally, one-fifth of clinics offer urethral microscopy to asymptomatic heterosexual men and MSM, and about one half of clinics offer urethral culture for detection of gonorrhoea in asymptomatic women, even though these practices are not compliant with the guidelines.

A national audit of screening of asymptomatic patients seen in UK genitourinary medicine clinics in 2009 was conducted against the national guidelines. Data were aggregated by regions and clinics in regions, allowing practice to be compared within and between regions, as well as to national averages and against national guidelines. The case-notes of 4428 patients were audited. Performance was over 80% against the national guidelines for screening of asymptomatic heterosexual men, men who have sex with men (MSM) and women for chlamydial, gonorrhoeal, syphilis and HIV infections. However, the recommended method of endocervical culture for gonorrhoea was performed in only 65% of women, with a further one-quarter being screened with endocervical or vulvovaginal nucleic acid amplification tests (NAATs). Although significant NAAT use for gonorrhoea was seen in all groups, testing for gonorrhoea by culture is still recommended as a first-line test on invasive samples. Over 80% of MSM, who were not known to be immune, were screened for hepatitis B. Urethral microscopy was performed in 22% of heterosexual men and 17% of MSM, and cervical microscopy in 12% of women.

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.

We audited the effect of introducing HIV opt-out in a genitourinary medicine clinic in central London, UK. We found that opt-out increased the rate at which HIV testing was offered to low-risk patients and that more tests were done.

Objectives: To determine what proportion of men who have sex with men (MSM) attending genitourinary medicine (GUM) clinics are offered and accept an HIV test and to examine clinic and patient characteristics associated with offer and uptake., Methods: A cross-sectional study of all GUM clinics in the United Kingdom, involving a case note review of up to 30 patient records per clinic and the completion of a clinic policy form., Results: Overall, 86% of MSM were offered a test and of those 82% accepted a test. Attending with symptoms of a sexually transmitted infection (STI), fewer numbers of partners in the past three months and having tested previously were all independently associated with a decreased likelihood of being offered a test. Attending with symptoms of an STI, increasing age, never having had a risk from unprotected anal intercourse or a previous HIV test and increasing time to wait for results were all independently associated with a decreased likelihood of a patient accepting a test. Only a quarter of clinics reported a written policy for HIV testing intervals among MSM; however, all clinics reported offering testing to all new MSM patients at first screening. The testing policy for re-attending patients was less clear., Conclusions: Testing must reach those at most risk and those less likely to test in order to reduce further the proportion of undiagnosed HIV infection. This study suggests that opportunities to detect infection may be being missed and a move towards universal testing of all MSM attending with a new episode, as well as testing within the window period, is recommended.

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.

Faced with a national 48-hour waiting time target and high non-attendance rates for booked appointments, our sexual health service sought patient preferences for appointment reminders. Questionnaires were distributed to 350 consecutive genitourinary medicine clinic attendees. Eighty-eight percent of respondents approved of appointment reminders, with text messaging being the preferred option. Automated voicemail reminders to mobile phones were acceptable to 84%. Patients would generally choose a voicemail reminder to their mobile phone as opposed to home or work phone, and this preference was more pronounced in younger patients (P = 0.03). The majority of patients considered reminders two or three days in advance sufficient notice, with 98% owning a mobile phone. Text or voicemail reminders may significantly reduce non-attendance rates and their associated costs, improve accessibility and reduce waiting times.

Background: The fragile X premutation is characterized by a large CGG repeat track (55-199 repeats) in the 5' UTR of the FMR1 gene. This X-linked mutation leads to an increased risk for premature ovarian failure; interestingly, the association of repeat size with risk is non-linear. We hypothesize that the premutation-associated ovarian insufficiency is due to a diminished oocyte pool and examined reproductive aging milestones by repeat size group to determine if the same non-linear association is observed., Methods: We analyzed cross-sectional reproductive history questionnaire data from 948 women with a wide range of repeat sizes., Results: We have confirmed the non-linear relationship among premutation carriers for ovarian insufficiency. The mid-range repeat size group (80-100 repeats), not the highest group, had an increased risk for: altered cycle traits (shortened cycle length, irregular cycles and skipped cycles), subfertility and dizygotic twinning. Smoking, a modifiable risk, decreased the reproductive lifespan of women with the premutation by about 1 year, similar to its effect on non-carriers. As expected, premutation carriers were found to be at an increased risk for osteoporosis., Conclusions: Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.

Background & Aims: Biliary atresia is an inflammatory, fibrosclerosing neonatal cholangiopathy, characterized by a periductal infiltrate composed of CD4(+) and CD8(+) T cells. The pathogenesis of this disease has been proposed to involve a virus-induced, subsequent autoreactive T cell-mediated bile duct injury. Antigen-specific T-cell immunity involves clonal expansion of T cells expressing similar T-cell receptor (TCR) variable regions of the beta-chain (Vbeta). We hypothesized that the T cells in biliary atresia tissue expressed related TCRs, suggesting that the expansion was in direct response to antigenic stimulation., Methods: The TCR Vbeta repertoire of T cells from the liver, extrahepatic bile duct remnants, and peripheral blood of biliary atresia and other cholestatic disease controls were characterized by fluorescent-activated cell sorter analysis, and TCR junctional region nucleotide sequencing was performed on expanded TCR Vbeta regions to confirm oligoclonality., Results: FACS analysis revealed Vbeta subset expansions of CD4(+) and CD8(+) T cells from the liver or bile duct remnant in all patients with biliary atresia and only 1 control. The CD4(+) TCR expansions were limited to Vbeta3, -5, -9, and -12 T-cell subsets and the CD8(+) TCR Vbeta expansions were predominantly Vbeta20. Each Vbeta subset expansion was composed of oligoclonal populations of T cells., Conclusions: Biliary atresia is associated with oligoclonal expansions of CD4(+) and CD8(+) T cells within liver and extrahepatic bile duct remnant tissues, indicating the presence of activated T cells reacting to specific antigenic stimulation. Future studies entail identifying the specific antigen(s) responsible for T-cell activation and bile duct injury.

Background: Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection., Design: Chronically infected patients with low CD4 counts T-cell counts who commenced antiretroviral therapy (ART) were subsequently treated with combined interleukin-2 and therapeutic vaccination., Methods: Thirty six anti-retroviral naive patients were recruited and initiated on combination ART for 17 weeks before randomization to: A) ongoing ART alone; B) ART with IL-2 twice daily for 5 days every four weeks starting at week 17 for 3 cycles; C) ART with IL-2 as in group B and Remune HIV-1 vaccine administered once every 3 months, starting at week 17; and D) ART with Remune vaccine as in group C. Patients were studied for 65 weeks following commencement of ART, with an additional prior 6 week lead-in observation period. CD4 and CD8 T-cell counts, evaluations of HIV-1 RNA levels and proliferative responses to recall and HIV-1 antigens were complemented with assessment of IL-4-secretion alongside quantification of anti-HIV-1 CD8 T-cell responses and neutralizing antibody titres., Results: Neither IL-2 nor Remune vaccination induced sustained HIV-1-specific T-cell responses. However, we report an inverse relationship between HIV-1-specific proliferative responses and IL-4 production which continuously increased in patients receiving immunotherapy, but not patients receiving ART alone., Conclusion: Induction of HIV-1-specific cell-mediated responses is a major challenge in chronically HIV-1-infected patients even when combining immunisation with IL-2 therapy. An antigen-specific IL-4-associated suppressive response may play a role in attenuating HIV-specific responses.

Objective: To assess the effectiveness of a text message result service within an inner London sexual health clinic., Method: Demographic data, diagnoses, and time to diagnosis and treatment were collected over a 6 month period for patients receiving text messages and a matched standard recall group. Data on messages sent, staff time, and cost in relation to result provision were collected., Results: Over a 6 month period 952 text messages were sent. In the final month of analysis, 33.9% of all clinic results were provided by text, resulting in a saving of 46 hours of staff time per month. 49 messages requested that the patient return for treatment, 28 of these patients had untreated genital Chlamydia trachomatis (CT) infection. The mean number of days (SD) to diagnosis was significantly shorter in the text message group (TG) v the standard recall group (SG) (7.9 (3.6) v 11.2 (4.7), p <0.001). The median time to treatment was 8.5 days (range 4-27 days) for the TG group v 15.0 (range 7-35) for SG, p = 0.005., Conclusion: Patients with genital CT infection are diagnosed and receive treatment sooner since the introduction of a text message result service. The introduction of this service has resulted in a significant saving in staff time.

Chronic beryllium disease (CBD) is characterized by a CD4+ T cell alveolitis and granulomatous inflammation in the lung. Genetic susceptibility to this disease has been linked with HLA-DP alleles, particularly those possessing a glutamic acid at position 69 (Glu69) of the beta-chain. However, 15% of CBD patients do not possess a Glu69-containing HLA-DP allele, suggesting that other MHC class II alleles may be involved in disease susceptibility. In CBD patients without a Glu69-containing HLA-DP allele, an increased frequency of HLA-DR13 alleles has been described, and these alleles possess a glutamic acid at position 71 of the beta-chain (which corresponds to position 69 of HLA-DP). Thus, we hypothesized that beryllium presentation to CD4+ T cells was dependent on a glutamic acid residue at the identical position of both HLA-DP and -DR. The results show that HLA-DP Glu69- and HLA-DR Glu71-expressing molecules are capable of inducing beryllium-specific proliferation and IFN-gamma expression by lung CD4+ T cells. Using fibroblasts expressing mutated HLA-DP2 and -DR13 molecules, beryllium recognition was dependent on the glutamic acid at position 69 of HLA-DP and 71 of HLA-DR, suggesting a critical role for this amino acid in beryllium presentation to Ag-specific CD4+ T cells. Thus, these results demonstrate that a single amino acid residue of the MHC class II beta-chain dictates beryllium presentation and potentially, disease susceptibility.

Beryllium exposure can lead to the development of beryllium-specific CD4+ T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4+ T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4+ T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the 2 types of responses was poor. We hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4+ T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, we found a direct correlation between the percentage of beryllium-specific CD4+ T(EM) cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4+ T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement.

Background: CYP17, which encodes cytochrome P450c17alpha, mediates both steroid 17alpha-hydroxylase and 17,20-lyase activities, and is essential for the production of glucocorticoids and sex steroids. There is evidence that a common polymorphism in CYP17 (T27C) is associated with estrogen levels, making it a potential marker of disease risk., Methods: This is the first study to examine the relationship between CYP17 and estradiol (E2) using serum sampled exclusively from the early follicular phase of the menstrual cycle. We assessed the relationship between CYP17 and serum hormone levels, menstrual cycle length, bleed length, and age at menarche in 164 pre-menopausal women., Results: Among women with body mass index (BMI) < or =25 kg/m2, those with the TC and CC genotypes had 19 and 42% higher E2 (P for trend 0.007) and 14 and 30% higher dehydroepiandrosterone sulphate respectively (P for trend 0.10) than women with the TT genotype. Androstenedione levels did not differ between genotypes. Among women with BMI >25 kg/m2, hormone levels did not differ by genotype. Women with the C allele were also more likely to have menstrual cycle lengths <27 days [odds ratio (OR) for TC=2.36, 95% confidence interval (CI)=1.24-4.52; OR for CC=5.59, 95% CI=1.53-20.43 compared to TT]. CYP17 genotype was not associated with menstrual bleed length or age at menarche., Conclusion: The CYP17 T27C polymorphism may be a marker of endocrine function.

Background: Beryllium sensitization is caused by exposure to beryllium in the workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and granulomatous inflammation. Whether biomarkers are present in blood that would allow separation of CBD from beryllium sensitization without invasive pulmonary procedures is unknown., Objective: The aim of this study was to determine whether the quantity of beryllium-specific T cells in blood of patients with CBD differs from that found in BeS subjects., Methods: Beryllium-induced T-cell proliferation and T H 1-type cytokine secretion were determined in blood cells from 33 patients with CBD and 18 BeS subjects., Results: We demonstrate here that patients with CBD have a significantly elevated number of IFN-gamma-producing and IL-2-producing beryllium-specific CD4+ T cells in blood compared with both BeS and normal control subjects. In contrast, no difference in beryllium-induced proliferation of blood T cells was seen between BeS patients and patients with CBD. Compared with the blood beryllium lymphocyte proliferation test, which detected beryllium-induced proliferation in 65% of BeS patients and patients with CBD, ELISPOT analysis detected IFN-gamma secretion in 80% of these subjects. Higher numbers of beryllium-specific cells in blood were also associated with the extent of alveolar inflammation, as measured by both bronchoalveolar lavage white blood cell and lymphocyte counts., Conclusion: The frequency of beryllium-specific T cells in the blood of beryllium-exposed subjects may be a useful biomarker that helps discriminate between beryllium sensitization and progression to CBD.

Background: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk., Methods: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes., Results and Conclusions: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats).

HIV-1 infection results in profound dysfunction of the CD4 T-cell population. Although highly active antiretroviral therapy allows the reconstitution of CD4 T-cell numbers, functional abnormalities remain, including inadequate responses to vaccination. IL-2 increases CD4 T-cell numbers and function. We report the effects of IL-2 given with tetanus vaccination in two patients in a larger immunotherapy study. In one case IL-2 induced sustained responses, which may have been caused by the timing of IL-2 with vaccination.

Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.

Delirium is a frequent complication of cancer treatment and is associated with a high incidence of morbidity and mortality. This article summarizes recent literature on the epidemiology, mechanisms, and treatment of delirium in the patient with cancer. As data continue to emerge on risk factors and pathophysiological mechanisms, recognition of the distinctive features of delirium in specific cancer populations could contribute to a better understanding of consciousness, cognition, perception, and behavior during medical illness.

The effect of altering antiretroviral therapy (ART) on responses to viral, recall and human immunodeficiency virus (HIV)-1-specific recombinant antigens and interleukin-2 (IL-2) in HIV-1-infected patients was assessed. A longitudinal cohort study in eight HIV-1 infected individuals following a clinically indicated therapy change (seven for drug intolerance and one for virological failure) from protease inhibitor (PI) to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral regimens was performed. CD4 T-cell counts, viral loads, lymphoproliferative responses, cytokine production and latent proviral deoxyribonucleic acid (DNA) were measured at baseline and at weeks 12 and 24 after therapy substitution. Following therapy-switch there was a 33% proportional increase in mitogen response (95% confidence interval (CI), 3-33%) and a 31% increase (95% CI, 15-48%) in viral and recall-antigen responses. Six patients developed proliferative responses to low concentration IL-2 stimulation. All patients demonstrated an increase in median HIV-1-specific responses, as three had detectable virus at baseline (two being viral rebound); this may reflect an autovaccination effect. Proviral DNA changes largely reflected plasma HIV-1 ribonucleic acid (RNA). In conclusion, NNRTI substitution for a PI may favour immune reconstitution with an improvement in HIV-1-specific responses, which may reflect differential effects on antigen processing and presentation, an autovaccination effect or alternatively a potential suppressive effect of the PI.

The combination of intermittent subcutaneous IL-2 and highly active antiretroviral therapy in individuals infected with HIV-1 has been shown to have a beneficial quantitative effect on the CD4 T cell count. We observed IL-2-associated viral load 'blips' inducing HIV-1-specific lymphoproliferative responses at 24 weeks in such individuals. This immunotherapeutic approach, utilizing autologous virus as autovaccination, may be a viable, safer alternative to structured treatment interruption and potentially more efficacious than therapeutic vaccines.

Interleukin-16 (IL-16) and the beta-chemokines (RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein (MIP)-1alpha and (MIP)-1beta) are soluble in vitro suppressors of macrophage tropic HIV-1 strains. The reduction of HIV-1 RNA plasma levels in late-stage patients receiving protease inhibitors has been associated with increased concentrations of MIP-1alpha, MIP-1beta, RANTES and IL-16 and a decrease in levels of MCP-1. We determined plasma levels of MCP-1, MIP-1alpha, MIP-1beta, RANTES and IL-16 during the first 16 weeks of highly active antiretroviral therapy (HAART) in chronic HIV-1-infected patients. Patients were administered one of two therapeutic regimens based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). No differences were seen in the levels of RANTES and IL-16 over the first 16 weeks of HAART in either treatment group. MCP-1 decreased significantly in the PI-treated group over the first 16 weeks of HAART (P = 0.0003). A significant increase was observed in the levels of MIP-1alpha and MIP-1beta in the NNRTI cohort (P = 0.0010 and P = 0.0012, respectively). A significant decrease in levels of MIP-1alpha and MIP-1beta (P = 0.0015 and P = 0.0299, respectively) was observed over the 16 weeks in the PI cohort. A significant difference was seen when the levels of MIP-1alpha and MIP-1beta were compared between the NNRTI and the PI cohorts at week 16 (P = 0.04 and P = 0.05, respectively). Evaluation of CCR5 expression ex vivo revealed no difference between the two treatment groups. Patients were genotyped for CCR5 Delta32 and the incidence of heterozygosity was lower than in the HIV-1 seronegative controls (3% compared to 19%).

Fragile X syndrome, a form of X-linked mental retardation, results from the hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. Relatively little is known about the initial mutation that causes a stable allele to become unstable and, eventually, to expand to the full mutation. In the present study, we have examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats) or intermediate (40-59 repeats) sizes to study the initial mutation events. Of these, 201 have been sequenced and haplotyped. Using logistic regression analysis, we found that parental origin of transmission, repeat size (for unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were significant risk factors for repeat instability. Interestingly, transmission of the repeat through males was less stable than that through females, at the common- and intermediate-size level. This pattern differs from that seen for premutation-size alleles: paternally transmitted alleles are far more stable than maternally transmitted alleles. This difference that depends on repeat size suggests either a different mutational mechanism of instability or an increase in selection against sperm as their repeat size increases.

Meningococcal infection is believed to be rare in HIV-positive individuals. We present 2 cases from our reference caseload within the last 10 years.

Purpose: In this study, our purpose was to assess the efficacy of nelfinavir- and nevirapine-containing salvage regimens in nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients virologically failing a protease inhibitor (PI)-based combination., Method: A retrospective case note review of all patients virologically failing their PI-based combination who were switched to a regimen containing both nelfinavir (1 g t.d.s.) and nevirapine (200 mg b.d.). CD4 cell counts and viral loads were monitored. Genotypic analysis was performed using RT-PCR sequencing., Results: Nineteen patients commenced a salvage regimen containing nelfinavir and nevirapine. Five patients also changed at least one nucleoside reverse transcriptase inhibitor (NRTI), although in one case this represented recycling. Thirty-eight percent (6/16) of patients achieved a viral load below the level of detection (BLD; <200 copies/mL; complete responders [CR]), 3 achieved <20 copies/mL. Five patients achieved > or =1 log drop (partial responders [PR]) that was not sustained over follow-up, and five failed to respond to therapy (nonresponders [NR]). CRs tended to have wild-type NNRTI and PI sequences relative to PRs and NRs., Conclusion: In heavily pretreated patients, a nelfinavir-and nevirapine-containing salvage regimen resulted in a virological response in 38% of patients that was sustained in 31% over 63 weeks.