Experiences of mpox illness and case management among cis and trans gay, bisexual and other men who have sex with men in England: a qualitative study.

Background: The 2022-2024 global mpox outbreak, occurring primarily in the sexual networks of gay, bisexual and other men who have sex with men (GBMSM), has not been accompanied by a focus on patient perspectives of illness. We explore the experiences of GBMSM diagnosed with mpox in England to understand needs for social and clinical support. Methods: In-depth interviews (March/July 2023) were conducted with 22 GBMSM diagnosed with mpox in 2022, randomly selected from a national mpox surveillance database, and 4 stakeholders from clinical/community-based organisations. Interviews covered experiences of illness, testing, diagnosis, treatment and contact tracing, and were recorded, transcribed and analysed with a thematic framework. Findings: Media coverage drawing on homophobic stereotypes around sex between men contributed to feelings of stigma and shame. GBMSM living with HIV appeared to cope better with mpox stigma, drawing on their experiences of being diagnosed with HIV for resilience. Younger GBMSM with less experience of stigmatising illness found mpox diagnosis more traumatic and sometimes required support beyond what was provided. Accessing testing could be complicated when healthcare professionals did not recognise mpox symptoms. Men felt information on course of illness, isolation and vaccination after recovery was often inconsistent and contradictory. GBMSM described that care from sexual health and infectious disease units usually better met their emotional and medical needs. This was frequently linked by men to these services having skills in working with the GBMSM community and managing infection risk sensitively. General hospital services and centralised contact tracing could increase feelings and experiences of stigma as some staff were perceived to lack skills in supporting GBMSM and, sometimes, clinical knowledge. Long-term impacts described by men included mental health challenges, urethral/rectal symptoms and life-changing disability. Interpretation: In this study stigma was a central feature of mpox illness among GBMSM and could be exacerbated or lessened depending on the clinical and social support provided. Involving communities affected by outbreaks in co-producing, planning and delivering care (including contact-tracing) may help improve support provided. Funding: TCW, AJR, AS and FMB received support from the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research Programme (Ref: NIHR202038). CS and JS receive support from the National Institute for Health and Care Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with UKHSA; RV receives support from the NIHR HPRU in Emerging and Zoonotic Infections and NIHR HPRU in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency, World Health Organization or the Department of Health and Social Care.

Advantages of a synchrotron light source for fluorescence-detected linear dichroism.

Fluorescence-detected linear dichroism (FD-LD) enables one to collect linear dichroism spectra for oriented fluorophores in the presence of other absorbing species and light scattering. The experiment proceeds by scanning the excitation wavelength and using a filter to collect only emitted photons from the fluorophore. Thus, it has the potential to give data with enhanced selectivity and quality. By using a synchrotron radiation light source and fluorescence-detection, we show data for a range of fluorophores in different orienting environments. Film and flow-oriented FD-LD spectra were collected down to 170 nm. Even for flow-oriented liposomes, we have data collected down to 210 nm. For strongly scattering samples, for example, liposomes, FD-LD has the clear advantage that scattering is absent for the longer wavelength fluorescence photons. The collimated and smaller beam size of the synchrotron radiation also gives rise to sharper and more well-defined features in the spectra.

Experiences with health care services and HIV testing after sexual assault in cisgender gay, bisexual and other men who have sex with men and transgender people.

OBJECTIVES: This qualitative sub-study aimed to explore how cisgender gay, bisexual, and other men who have sex with men (cis-GBMSM) and transgender people who reported non-consensual sex (NCS) accessed health care services, what barriers they faced, and how this experience influenced subsequent HIV testing. METHODS: SELPHI is an online randomized controlled trial evaluating both acceptability and efficiency of HIV-self testing among cis-GBMSM and transgender people. Semi-structured interviews were conducted, audio-recorded, transcribed, and analysed through a framework analysis, as a qualitative sub-study. We identified narratives of NCS from interviews and investigated experiences of cis-GBMSM and transgender people accessing health care services following sexual assault. RESULTS: Of 95 participants, 15 (16%) spontaneously reported NCS. Participants reported a broad range of NCS, including partner's coercive behaviours, non-consensual removal of condoms, and rapes. All feared HIV transmission, leading them to test for HIV, underlining a marked lack of awareness of post-exposure prophylaxis (PEP). Most had negative experiences in communicating with reception staff in sexual health clinics following these incidents. A lack of confidentiality and empathy was described in these situations of psychological distress. Clinic visits were primarily focused on testing for HIV and sexually transmitted infection, and generally no specific psychological support was offered. Getting a negative HIV result was a key step in regaining control for people who experienced NCS. CONCLUSIONS: Sexual health care providers should take care to more fully address the issue of NCS with cis-GBMSM and transgender people when it arises. Recognizing and managing the emotional impact of NCS on affected patients would prevent negative experiences and increase confidence in care.

Linear dichroism and linearly polarised luminescence spectra of oriented samples collected on a new integrated instrument.

Linearly polarised luminescence (LPL) has a wide range of potential applications giving optical and geometric parameters for oriented lumiphores. In this work we present the first wavelength scanned LPL spectra. Analytes are either oriented on stretched polyethylene films or in flow. Applications of the wavelength-dependence of g-factors are illustrated.

Quantifying non-adherence to anti-tuberculosis treatment due to early discontinuation: a systematic literature review of timings to loss to follow-up.

BACKGROUND: The burden of non-adherence to anti-tuberculosis (TB) treatment is poorly understood. One type is early discontinuation, that is, stopping treatment early. Given the implications of early discontinuation for treatment outcomes, we undertook a systematic review to estimate its burden, using the timing of loss to follow-up (LFU) as a proxy measure. METHODS: Web of Science, Embase and Medline were searched up to 14 January 2021 using terms covering LFU, TB and treatment. Studies of adults (≥ 18 years) on the standard regimen for drug-sensitive TB reporting the timing of LFU (WHO definition) were included. A narrative synthesis was conducted and quality assessment undertaken using an adapted version of Downs and Black. Papers were grouped by the percentage of those who were ultimately LFU who were LFU by 2 months. Three groups were created: <28.3% LFU by 2 months, ≥28.3-<38.3%, ≥38.3%). The percentage of dose-months missed due to early discontinuation among (1) those LFU, and (2) all patients was calculated. RESULTS: We found 40 relevant studies from 21 countries. The timing of LFU was variable within and between countries. 36/40 papers (90.0%) reported the percentage of patients LFU by the end of 2 months. 31/36 studies (86.1%) reported a higher than or as expected percentage of patients becoming LFU by 2 months. The percentage of dose-months missed by patients who became LFU ranged between 37% and 77% (equivalent to 2.2-4.6 months). Among all patients, the percentage of dose-months missed ranged between 1% and 22% (equivalent to 0.1-1.3 months). CONCLUSIONS: A larger than expected percentage of patients became LFU within the first 2 months of treatment. These patients missed high percentages of dose months of treatment due to early discontinuation. Interventions to promote adherence and retain patients in care must not neglect the early months of treatment. PROSPERO REGISTRATION NUMBER: CRD42021218636.

Integrated Circular Dichroism and Circularly Polarized Luminescence Measurements.

Circularly polarized luminescent (CPL) systems have a plethora of potential applications owing to their interesting excited-state properties. However, the progress in developing new chiral luminescence systems is significantly hindered by the lack of available instrumentation for the broader chemistry and materials science community to perform routine, reproducible measurements of chiral spectroscopies. In this work, we present data from an easy-to-use custom-built instrument based on a Jasco circular dichroism (CD) spectropolarimeter coupled with a CPL emission monochromator (CD/CPL hybrid system). The hybrid system measures CPL, fluorescence, CD, and absorbance on the same part of the sample without the need to move between the CD and CPL measurements. The instrument uses a xenon arc lamp as the light source, enabling a wide range of excitation wavelengths to support flexible development of new molecules and materials. Data obtained and presented for camphor, ruthenium metal complexes, the peptide gramicidin, and a DNA-ligand (4',6-diamidino-2-phenylindole, DAPI) system in this work highlight the ease of use and reproducibility of the results. The g-factors for CD and CPL obtained for the different compounds are shown to be the same for isolated transitions and some examples of how to use variations of g-factors with wavelength are demonstrated. The reliable and excellent benchmark results obtained from a custom-built commercial wavelength scanning CPL/CD hybrid instrument open up new avenues for the broader chemical and materials science community to intensify research on chiral luminescent systems.

Nanofluidic point-of-care IgE test for subtropical grass pollen for rapid diagnosis of allergic rhinitis.

BACKGROUND: Widening of subtropical climate zones globally and increasing grass-pollen exposure provide the impetus for developing a more precise and accessible diagnosis of allergy. OBJECTIVE: To evaluate the utility of recombinant allergen components of Panicoideae and Chloridoideae pollens for specific IgE testing in a rapid, point-of-care device. METHODS: Recombinant (r) Pas n 1 and Cyn d 1 were expressed, purified, and tested in the nanofluidic device for measuring serum specific IgE (spIgE) in a well-characterized Australian cohort. Concentrations and classes of spIgE to rPas n 1 and rCyn d 1, and total IgE were compared with skin prick test results and spIgE with grass pollen. RESULTS: Correlations between commercial and academic laboratories for 21 sera were high for rPas n 1 spIgE (r = 0.695) and total IgE (r = 0.945). Higher spIgE to rPas n 1 and rCyn d 1 fluorescence was detected in the patients with grass-pollen allergy and with clinician-diagnosed allergic rhinitis (n = 134) than in participants with other allergies (n = 49) or no allergies (n = 23). Correlation between spIgE concentrations to rPas n 1 (r = 0.679) and rCyn d 1 (r = 0.548), with Bahia and Bermuda grass-pollen spIgE, respectively, was highly significant (p<0.0001). The positive/negative predictive agreements of spIgE classes for rPas n 1 (73%/82.5%) and rCyn d 1 (67.8%/66.3%) between the nanofluidic and ImmunoCAP measurements for Bahia and Bermuda grass pollen, respectively, were substantial. CONCLUSION: Point-of-care nanofluidic tests for spIgE to rPas n 1 and rCyn d 1 could increase access to more precise clinical diagnosis for patients with allergies in subtropical regions.

HIV pre-exposure prophylaxis and its implementation in the PrEP Impact Trial in England: a pragmatic health technology assessment.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. To enable routine commissioning of PrEP in England, we aimed to establish population need, duration of need, PrEP uptake, and duration of use in attendees of sexual health services (SHS) in England. METHODS: The Impact Trial was a prospective, open-label, single-arm, multicentre trial conducted at 157 SHS across England between Oct 13, 2017, and July 12, 2020. Clinicians assessed HIV-negative attendees for their risk of HIV acquisition to identify those who were eligible to participate and receive either daily or event-based oral PrEP (tenofovir disoproxil maleate with emtricitabine), as appropriate. Eligible participants were aged 16 years or older, considered HIV-negative on the day of enrolment, and willing to adhere to the trial procedures. Non-trial attendees are mutually exclusive of trial participants and included SHS attendees who were not recruited to the Impact Trial at any point. They include HIV-negative individuals aged 16 years or older who attended a participating SHS at least once after recruitment at that SHS had begun and before Feb 29, 2020. The main outcomes assessed were PrEP need, uptake, and use, and HIV and sexually transmitted infection (STI) incidence. Data are presented up to Feb 29, 2020, before the introduction of COVID-19 control measures. The study is registered with ClinicalTrials.gov, NCT03253757. FINDINGS: In this analysis, we include 21 356 of 24 268 participants enrolled before Feb 29, 2020. 20 403 participants (95·5%) were men who have sex with men (MSM). Uptake of PrEP among SHS attendees clinically assessed and coded as eligible was 21 292 (57·1%) of 37 289. 18 400 trial participants had at least one post-enrolment visit and a median of 361 days of follow-up (IQR 143-638); 14 039 (75·9%) of these had enough PrEP prescribed to provide protection for 75% of their follow-up time. Among MSM, HIV incidence was 0·13 (95% CI 0·08-0·19) per 100 person-years in trial participants (27 seroconversions) and 0·95 (95% CI 0·88-1·03) per 100 person-years in non-trial attendees (587 seroconversions; proportionate reduction of 86·8%, 95% CI 80·2-91·6). 18 607 bacterial STIs were recorded (incidence 68·1 per 100 person-years in trial participants who were MSM). 4343 (24·4%) MSM participants were diagnosed with two or more STIs, accounting for 14 800 (79·5%) of all 18 607 diagnoses. INTERPRETATION: PrEP need was higher than initially estimated by an expert stakeholder group. The high proportion of follow-up time protected by PrEP suggests that the need for protection persisted throughout trial participation for most participants. HIV incidence among MSM trial participants was low. The large unmet need for PrEP suggests that greater provision is required to maximise the potential of a national programme. The high incidence of bacterial STIs among participants, concentrated within a subgroup of PrEP users, presents an opportunity for tailored STI control measures. FUNDING: NHS England.

The effect of combination prevention strategies on HIV incidence among gay and bisexual men who have sex with men in the UK: a model-based analysis.

BACKGROUND: In the UK, the number of new HIV diagnoses among gay and bisexual men who have sex with men (GBMSM) has decreased substantially. We aimed to understand the contribution of different interventions in reducing HIV incidence so far; to estimate future HIV incidence with continuation of current policies and with further scaling up of current interventions; and to estimate the maximum additional annual cost that should be spent towards these interventions for them to offer value for money. METHODS: We calibrated a dynamic, individual-based, stochastic simulation model, the HIV Synthesis Model, to multiple sources of data on HIV among GBMSM aged 15 years or older in the UK. Primarily these were routine HIV surveillance data collected by the UK Health Security Agency. We compared HIV incidence in 2022 with the counterfactual incidence: if HIV testing rates stopped increasing in 2012 and the policy of antiretroviral therapy (ART) at diagnosis was not introduced in mid-2015; if pre-exposure prophylaxis (PrEP) was not introduced; if condom use was low from 2012 in all GBMSM, at levels similar to those observed in 1980; and in the first and second scenario combined. We also projected future outcomes under the assumption of continuation of current policies and considering increases in PrEP and HIV testing uptake and a decrease in condomless sex. FINDINGS: Our model estimated a 77% (90% uncertainty interval [UI] 61-88) decline in HIV incidence since around 2014, with an estimated 597 infections ([90% UI 312-956]; 1·1 per 1000 person-years [90% UI 0·6-1·8]) in men aged 15-64 years in 2022. Both PrEP introduction and increased HIV testing with ART initiation at diagnosis each had a substantial effect on HIV incidence. Without PrEP introduction, we estimate there would have been 2·16 times the number of infections that actually occurred (90% UI 1·06-3·75) between 2012 and 2022; without increased HIV testing and ART initiation at diagnosis there would have been 2·18 times the number of infections that actually occurred (1·18-3·60), and if condomless sex was at the levels before the HIV epidemic, there would have been 2·27 times the number of infections that actually occurred (0·9-5·4). If rates of testing, ART use, and PrEP use remain as they are currently, there is a predicted decline in incidence to 388 HIV infections in 2025 (90% UI 226-650) and to 263 (137-433) in 2030. Increases in HIV testing and PrEP use were predicted to accelerate the decline in HIV incidence. Given the quality-adjusted life-year (QALY) benefit and a cost-effectiveness threshold of £30 000 per QALY gained, in order to be cost-effective an additional £1·62 million could be spent per year to increase testing levels by 34% (90% UI 25-46) and PrEP use by 55% (10-107). To achieve that, a 16% reduction in the cost of delivery of testing and PrEP would be required. INTERPRETATION: Combination prevention, including a PrEP strategy, played a major role in the reduction in HIV incidence observed so far in the UK among GBMSM. Continuation of current activities should lead to a continued decline; however, it is unlikely to lead to reaching the target of fewer than 50 HIV infections per year among GBMSM by 2030. It will be important to reduce costs for testing and PrEP for their continued expansion to be cost-effective. FUNDING: National Institute for Health Research under its Programme Grants for Applied Research Programme and Medical Research Council-UK Research and Innovation.

New Approaches to Stretched Film Sample Alignment and Data Collection for Vibrational Linear Dichroism.

Rapid measurements of vibrational linear dichroism (VLD) infrared spectra are shown to be possible by using stretched polymer films and an extension of existing instrumentation designed for vibrational circular dichroism spectroscopy. Earlier techniques can be extended using additional inexpensive polymer substrates to record good-quality VLD spectra of a significantly wider range of compounds with comparatively short sample-preparation times. The polymer substrates used, polyethylene and polytetrafluoroethylene, are commonly available and inexpensive, and samples are more easily prepared than that for many earlier stretched-film and crystal studies. Data are presented for neutral hydrophobic organic molecules on hydrophobic films including acridine, anthracene, fluorene, and recently synthesized S-(4-((4-cyanophenyl)ethynyl)phenyl)ethanethioate. We extend the approach to polar or ionic species, including 2,2'-bipyridine, 1,10-phenanthroline, and sodium dodecyl sulfate, by oxidizing polyethylene films to change their wetting properties. The combination of new instrumentation and modified sample preparation methods is useful in basic spectroscopy for untangling and assigning complicated infrared spectra. Nevertheless, it is not a panacea as surface-adsorbed molecules are often not monodispersed, and higher analyte concentrations can lead to aggregation and resonance phenomena that have previously been observed for infrared spectra on surfaces. These effects can be assessed by varying the sample concentration. The focus of this paper is experimental, and detailed analysis of most of the spectra lies outside its scope, including some well-studied compounds such as acridine and anthracene that allow comparisons with earlier research.

Shape-Induced Variations in Aromatic Thiols Adsorption on Gold Nanoparticle: A Novel Method for Accurate Evaluation of Adsorbed Molecules.

Nonspherical gold nanoparticles (GNPs) are increasingly used to enhance sensitivity and selectivity in analytical methods such as surface-enhanced Raman spectroscopy (SERS) for detecting trace biomarkers. However, there is limited research on the adsorption properties of aromatic thiols onto gold nanoparticles of different morphologies, where surface curvature varies significantly at the molecular level. In this study, we investigated the adsorption kinetics of 4-mercaptobenzoic acid, an aromatic molecule, on GNPs with different shapes using SERS. Our findings revealed significant differences in the adsorption behavior and binding site preferences of aromatic thiols on GNPs with distinct morphologies. While thiol molecules consider any surface site on nanospheres equally appealing, nanostars exhibit variations in curvature and surface energy, leading to initial binding with further repositioning from the tips of the nanostar after plasmon activation. To address these differences, we proposed a universal method to evaluate the quantity of tightly bound adsorbed molecules on GNPs independently of the particle size, shape, or concentration.

Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis.

BACKGROUND: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV. METHODS: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV. FINDINGS: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios. INTERPRETATION: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects. FUNDING: Bill & Melinda Gates Foundation to the HIV Modelling Consortium.

Estimating the hospital costs of care for people living with HIV in England using routinely collected data.

BACKGROUND: Understanding the health care activity and associated hospital costs of caring for people living with HIV is an important component of assessing the cost effectiveness of new technologies and for budget planning. METHODS: Data collected between 2010 and 2017 from an English HIV treatment centre were combined with national reference costs to estimate the rate of hospital attendances and costs per quarter year, according to demographic and clinical factors. The final dataset included records for 1763 people living with HIV, which was analysed using negative binomial regression models and general estimating equations. RESULTS: People living with HIV experienced an unadjusted average of 0.028 (standard deviation [SD] 0.20) inpatient episodes per quarter, equivalent to one every 9 years, and 1.85 (SD 2.30) outpatient visits per quarter. The unadjusted mean quarterly cost per person with HIV (excluding antiretroviral drug costs) was £439 (SD 604). Outpatient appointments and inpatient episodes accounted for 88% and 6% of total costs, respectively. In adjusted models, low CD4 count was the strongest predictor of inpatient stays and outpatient visits. Low CD4 count and new patient status (having a first visit at the Trust in the last 6 months) were the factors that most increased estimated costs. Associations were weaker or less consistent for demographic factors (age, sex/sexual orientation/ethnicity). Sensitivity analyses suggest that the findings were generally robust to alternative parameter and modelling assumptions. CONCLUSION: A number of factors predicted hospital activity and costs, but CD4 cell count and new patient status were the strongest. The study results can be incorporated into future economic evaluations and budget impact assessments of HIV-related technologies.

Understanding experiences of potential harm among MSM (cis and trans) using HIV self-testing in the SELPHI randomised controlled trial in England and Wales: a mixed-methods study.

BACKGROUND: The potential of HIV self-testing (HIVST) to cause harm is a concern hindering widespread implementation. The aim of this paper is to understand the relationship between HIVST and harm in SELPHI (An HIV Self-testing Public Health Intervention), the largest randomised trial of HIVST in a high-income country to date. METHODS: 10 111 cis and trans men who have sex with men (MSM) recruited online (geolocation social/sexual networking apps, social media), aged 16+, reporting previous anal intercourse and resident in England or Wales were first randomised 60/40 to baseline HIVST (baseline testing, BT) or not (no baseline testing, nBT) (randomisation A). BT participants reporting negative baseline test, sexual risk at 3 months and interest in further HIVST were randomised to three-monthly HIVST (repeat testing, RT) or not (no repeat testing, nRT) (randomisation B). All received an exit survey collecting data on harms (to relationships, well-being, false results or being pressured/persuaded to test). Nine participants reporting harm were interviewed in-depth about their experiences in an exploratory substudy; qualitative data were analysed narratively. RESULTS: Baseline: predominantly cis MSM, 90% white, 88% gay, 47% university educated and 7% current/former pre-exposure prophylaxis (PrEP) users. Final survey response rate was: nBT=26% (1056/4062), BT=45% (1674/3741), nRT=41% (471/1147), RT=50% (581/1161).Harms were rare and reported by 4% (n=138/3691) in exit surveys, with an additional two false positive results captured in other study surveys. 1% reported harm to relationships and to well-being in BT, nRT and RT combined. In all arms combined, being pressured or persuaded to test was reported by 1% (n=54/3678) and false positive results in 0.7% (n=34/4665).Qualitative analysis revealed harms arose from the kit itself (technological harms), the intervention (intervention harms) or from the social context of the participant (socially emergent harms). Intervention and socially emergent harms did not reduce HIVST acceptability, whereas technological harms did. DISCUSSION: HIVST harms were rare but strategies to link individuals experiencing harms with psychosocial support should be considered for HIVST scale-up. TRIAL REGISTRATION NUMBER: ISRCTN20312003.

Predictors of starting and stopping chemsex in men who have sex with men in England: findings from the AURAH2 prospective study.

BACKGROUND: Chemsex (the use of psychoactive drugs in sexual contexts) has been associated with HIV acquisition and other STIs, so there is benefit in identifying those most likely to start chemsex to offer risk reduction interventions such as pre-exposure prophylaxis (PrEP). To date, there have been no data from a longitudinal study analysing factors most associated with starting and stopping chemsex. METHODS: The prospective cohort study, Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2), collected 4 monthly and annual online questionnaire data from men who have sex with men (MSM) from 2015 to 2018. We investigate the association of sociodemographic factors, sexual behaviours and drug use with starting and stopping chemsex among 622 men who completed at least one follow-up questionnaire. Poisson models with generalised estimating equations were used to produce risk ratios (RRs) accounting for multiple starting or stopping episodes from the same individual. Multivariable analysis was adjusted for age group, ethnicity, sexual identity and university education. FINDINGS: In the multivariable analysis, the under 40 age group was significantly more likely to start chemsex by the next assessment (RR 1.79, 95% CI 1.12 to 2.86). Other factors which showed significant association with starting chemsex were unemployment (RR 2.10, 95% CI 1.02 to 4.35), smoking (RR 2.49, 95% CI 1.63 to 3.79), recent condomless sex (CLS), recent STI and postexposure prophylaxis (PEP) use in the past year (RR 2.10, 95% CI 1.33 to 3.30). Age over 40 (RR 0.71, 95% CI 0.51 to 0.99), CLS, and use of PEP (RR 0.64, 95% CI 0.47 to 0.86) and PrEP (RR 0.47, 95% CI 0.29 to 0.78) were associated with lower likelihood of stopping chemsex by the next assessment. INTERPRETATION: Knowledge of these results allows us to identify men most likely to start chemsex, thus providing an opportunity for sexual health services to intervene with a package of risk mitigation measures, especially PrEP use.

Couette flow fluorescence detected linear dichroism for analytes in lipid bilayers.

Membranes are important sites of intermolecular interactions in biological systems. However, they present significant analytical challenges as they contain multiple analytes and are dynamic in nature. In this work, we show how a Jasco J-1500 circular dichroism spectropolarimeter can be used with a microvolume Couette flow cell and appropriate cut-off filters to measure excitation fluorescence detected linear dichroism (FDLD) of fluorophores embedded in liposomal membranes. The result is a spectrum that selectively probes the fluorophore(s) and eliminates the scattering that is apparent in the corresponding flow linear dichroism (LD) spectrum. The FDLD spectrum is opposite in sign from the LD spectrum with relative magnitudes modified by the quantum yields of the transitions. FDLD thus enables analyte orientations to be identified in a membrane. Data for a membrane peptide, gramicidin, and two aromatic analytes, anthracene and pyrene, are presented. Issues with the "leakage" of photons by the long pass filters used is also discussed.

Electronic health records to capture primary outcome measures: two case studies in HIV prevention research.

BACKGROUND: There is increasing interest in the use of electronic health records (EHRs) to improve the efficiency and cost-effectiveness of clinical trials, including the capture of outcome measures. MAIN TEXT: We describe our experience of using EHRs to capture the primary outcome measure - HIV infection or the diagnosis of HIV infection - in two randomised HIV prevention trials conducted in the UK. PROUD was a clinic-based trial evaluating pre-exposure prophylaxis (PrEP), and SELPHI was an internet-based trial evaluating HIV self-testing kits. The EHR was the national database of HIV diagnoses in the UK, curated by the UK Health Security Agency (UKHSA). In PROUD, linkage to the UKHSA database was performed at the end of the trial and identified five primary outcomes in addition to the 30 outcomes diagnosed by the participating clinics. Linkage also produced an additional 345 person-years follow-up, an increase of 27% over clinic-based follow-up. In SELPHI, new HIV diagnoses were primarily identified via UKHSA linkage, complemented by participant self-report through internet surveys. Rates of survey completion were low, and only 14 of the 33 new diagnoses recorded in the UKHSA database were also self-reported. Thus UKHSA linkage was essential for capturing HIV diagnoses and the successful conduct of the trial. CONCLUSIONS: Our experience of using the UKHSA database of HIV diagnoses as a source of primary outcomes in two randomised trials in the field of HIV prevention was highly favourable and encourages the use of a similar approach in future trials in this disease area.

Falling treatment uptake in the hepatitis C care cascade is a growing threat to achieving elimination.

Most high-income countries are not on track to achieve the World Health Organization hepatitis C elimination targets. As elimination programmes assess growing proportions of patients in community-based pathways, rates of treatment uptake may fall. We aimed to identify factors associated with DAA treatment uptake and measure changes in their prevalence over time. We performed a time-to-treatment analysis on 2728 patients approved for hepatitis C Direct-Acting Antiviral treatment in the North Central London region between January 2016 and October 2019. We investigated the association between treatment uptake and factors including assessment/treatment setting (hospital, drug service or prison), patient age, gender, injection drug use, harmful alcohol use, cirrhosis status and previous treatment. The likelihood of treatment uptake was reduced by three independent risk factors. These included assessment setting: prison-based or drug-service pathways (aHR 0.29 or 0.81 vs. hospital outpatient pathway, 95% CI 0.21-0.40 and 0.70-0.94 respectively, p < .001); being UK-born (aHR 0.89 vs. non-UK born, 0.82-0.98, p = .01); and history of harmful alcohol use (aHR 0.84 vs. no history, 0.72-0.99, p = .04). The average number of these risk factors for not starting treatment per patient increased over time (R2  = 0.66 p < .001). Independent of these, there was an additional 5% reduction in rate of treatment initiation in each successive year of the programme (aHR 0.95, 0.91-0.99, p = .02). In conclusion, disengagement from care before treatment uptake was found to be a growing threat to elimination. Despite provision of community-based test-to-cure pathways, there are persistent barriers to treatment uptake and these are increasing over time.

Free HIV self-test for identification and linkage to care of previously undetected HIV infection in men who have sex with men in England and Wales (SELPHI): an open-label, internet-based, randomised controlled trial.

BACKGROUND: High levels of HIV testing in men who have sex with men remain key to reducing the incidence of HIV. We aimed to assess whether the offer of a single, free HIV self-testing kit led to increased HIV diagnoses with linkage to care. METHODS: SELPHI was an internet-based, open-label, randomised controlled trial that recruited participants via sexual and social networking sites. Eligibility criteria included being a man or trans woman (although trans women are reported separately); being resident in England or Wales, UK; being aged 16 years or older; having had anal intercourse with a man; not having a positive HIV diagnosis; and being willing to provide name, email address, date of birth, and consent to link to national HIV databases. Participants were randomly allocated (3:2) by computer-generated number sequence to receive a free HIV self-test kit (BT group) or to not receive this free kit (nBT group). Online surveys collected data at baseline, 2 weeks after enrolment (BT group only), 3 months after enrolment, and at the end of the study. The primary outcome was confirmed (linked to care) new HIV diagnosis within 3 months of enrolment, analysed by intention to treat. Those assessing the primary outcome were masked to allocation. This study is registered with the ISRCTN Clinical Trials Register, number ISRCTN20312003. FINDINGS: 10 111 participants (6049 in BT group and 4062 in nBT group) enrolled between Feb 16, 2017, and March 1, 2018. The median age of participants was 33 years (IQR 26-44 years); 9000 (89%) participants were White; 8118 (80%) participants were born in the UK; 81 (1%) participants were transgender men; 4706 (47%) participants were university educated; 1537 (15%) participants had never been tested for HIV; and 389 (4%) participants were taking pre-exposure prophylaxis. At enrolment, 7282 (72%) participants reported condomless anal sex with at least one male partner in the previous 3 months. In the BT group, of the 4511 participants for whom HIV testing information was available, 4263 (95%) reported having used the free HIV self-test kit within 3 months.Within 3 months of enrolment there were 19 confirmed new HIV diagnoses (0·31%) in 6049 participants in the BT group and 15 (0·37%) of 4062 in the nBT group (p=0·64). INTERPRETATION: The offer of a single, free HIV self-test did not lead to increased rates of new HIV diagnoses, which could reflect decreasing HIV incidence rates in the UK. Nonetheless, the offer of a free HIV self-testing kit resulted in high HIV testing rates, indicating that self-testing is an attractive testing option for a large group of men who have sex with men. FUNDING: UK National Institute for Health and Care Research.