HIV Self-testing for Men Who Have Sex With Men (MSM) in England and Wales: A multi-method study of self-testing intervention development and evaluation

Background: Undiagnosed HIV among men who have sex with men (MSM) remains a significant public health challenge in the UK. Higher rates of recent and repeat HIV testing are necessary to ensure recent falls in HIV incidence among MSM in parts of England and Wales are fully reproduced nationally. HIV self-testing (HIVST) is the latest in a long line of HIV testing interventions, which has been developed to reduce barriers to testing for those at risk of acquiring the virus. An HIV Self-testing Public Health Intervention (SELPHI) is the first randomised controlled trial (RCT) delivering free HIVST kits to MSM in Europe. SELPHI has two interventions and aims to assess whether HIVST can increase diagnosis of prevalent HIV infections (intervention A) and reduce the time between infection and diagnosis for those at on-going risk of new HIV infections (intervention B). Social sciences have been at the heart of SELPHI, contributing to formative, implementation and evaluation research. This thesis seeks to develop an understanding of the potential contribution of HIVST to the wellbeing of MSM in England & Wales. It contributes significantly to the academy by developing a comprehensive evidence base enabling policy makers and service providers to optimise HIVST service delivery. Methods: This work is conceptually grounded in implementation science and uses the Behaviour Change Wheel (BCW), which includes the COM-B model of behaviour change to provide a framework for intervention development and to understand participant outcomes. A pragmatic, multi-method approach has been taken whereby the optimal data collection methods have been carefully selected based on their suitability to answer the research questions. Results: This thesis includes three studies presented over five published papers. The first is a formative study (contributing to papers 1 and 2) of qualitative focus group discussions with MSM which produces new understandings of the diversity of their values and preferences with regard to HIVST. This study also interrogates narrative understandings of the potential use of the technology, demonstrating HIVST use may be limited to when MSM do not perceive significant risk, except in the context of significant barriers to service access. The second study (contributing to paper 3) is a mixed methods interrogation of the implementation pilot, demonstrating high feasibility and acceptability of an HIVST intervention delivered to MSM through the SELPHI study. The final study (contributing to papers 4 and 5) is an evaluative analysis of qualitative in-depth interviews with individuals who have undergone HIVST, showing high acceptability and varying intervention performance across groups. The utility of COM-B as a model for understanding behaviour change in relation to HIVST is examined in paper 5. Conclusions: Online delivery of HIVST to MSM is feasible and acceptable; contexts of use and intervention performance will vary across groups. A number of intervention adaptations can be made to increase acceptability and the potential reach of HIVST interventions. The absence of a robust concept of need in COM-B means that this model may be sub-optimal in designing HIVST interventions, and perhaps interventions which meet needs generated by social norms

Protocol, rationale and design of SELPHI: A randomised controlled trial assessing whether offering free HIV self-testing kits via the internet increases the rate of HIV diagnosis 11 Medical and Health Sciences 1117 Public Health and Health Services 11 Medical and Health Sciences 1103 Clinical Sciences

BACKGROUND: Among men who have sex with men (MSM) in the UK, an estimated 28% have never tested for HIV and only 27% of those at higher risk test at least every 6 months. HIV self-testing (HIVST), where the person takes their own blood/saliva sample and processes it themselves, offers the opportunity to remove many structural and social barriers to testing. Although several randomised controlled trials are assessing the impact of providing HIVST on rates of HIV testing, none are addressing whether this results in increased rates of HIV diagnoses that link to clinical care. Linking to care is the critical outcome because it is the only way to access antiretroviral treatment (ART). We describe here the design of a large, internet-based randomised controlled trial of HIVST, called SELPHI, which aims to inform this key question. METHODS/DESIGN: The SELPHI study, which is ongoing is promoted via social networking website and app advertising, and aims to enroll HIV negative men, trans men and trans women, aged over 16 years, who are living in England and Wales. Apart from the physical delivery of the test kits, all trial processes, including recruitment, take place online. In a two-stage randomisation, participants are first randomised (3:2) to receive a free baseline HIVST or no free baseline HIVST. At 3 months, participants allocated to receive a baseline HIVST (and meeting further eligibility criteria) are subsequently randomised (1:1) to receive the offer of regular (every 3 months) free HIVST, with testing reminders, versus no such offer. The primary outcome from both randomisations is a laboratory-confirmed HIV diagnosis, ascertained via linkage to a national HIV surveillance database. DISCUSSION: SELPHI will provide the first reliable evidence on whether offering free HIVST via the internet increases rates of confirmed HIV diagnoses and linkage to clinical care. The two randomisations reflect the dual objectives of detecting prevalent infections (possibly long-standing) and the more rapid diagnosis of incident HIV infections. It is anticipated that the results of SELPHI will inform future access to HIV self-testing provision in the UK. TRIAL REGISTRATION: DOI 10.1186/ISRCTN20312003 registered 24/10/2016

Risk, reassurance and routine: a qualitative study of narrative understandings of the potential for HIV self-testing among men who have sex with men in England

BACKGROUND: HIV testing has seen a rapid evolution over the last decade with multiple modalities now in use globally. In recent years HIV self-testing (HIVST) has been legalised in the UK paving the way for further expansion of testing. Interventions are delivered in particular social contexts which shape uptake. It is therefore important to understand how novel interventions are likely to be received by their intended users. This study aims to understand how HIVST compliments existing testing strategies considered or adopted by men who have sex with men (MSM). We do this by analysing normative discourses surrounding HIV testing and their perceptions of HIVST's potential future roles. METHODS: Six focus group discussions (FGDs) were conducted with 47 MSM in London, Manchester and Plymouth. One focus group included only MSM who reported higher risk behaviours and one with those who had never tested for HIV. Data were analysed through a thematic framework analysis. RESULTS: Three main narratives for testing for HIV were identified: (i) testing in response to a specific risk event; (ii) as reassurance when there was a small amount of doubt or anxiety related to HIV; and (iii) in response to social norms perpetuated through peers, HIV community groups and the medical establishment to test regularly for HIV. HIVST had limited utility for men when testing in response to specific risk events except in the case of significant structural barriers to other testing opportunities. HIVST was considered to have utility when seeking reassurance, and was thought to be very useful when testing to satisfy the needs and expectations of others around regular testing. There was some ambivalence about the incursion of a clinical intervention into the home. CONCLUSIONS: HIVST following risk events will likely be limited to those for whom existing service provision is insufficient to meet immediate needs based on structural or personal barriers to testing. Obligations of biological citizenship are central to MSM's understanding of the utility of HIVST. In the context of discourses of biocitizenship, men perceive HIVST to have dual roles: firstly as a tool to manage (mild) anxiety around one's HIV status based on an acknowledgment of HIV vulnerability arising from being homosexually active. Secondly, HIVST is useful in complying with social norms and meeting the perceived demands of biomedicine

Consolidating emerging evidence surrounding HIVST and HIVSS: A rapid systematic mapping protocol

BACKGROUND: HIV self-testing (HIVST) is becoming popular with policy makers and commissioners globally, with a key aim of expanding access through reducing barriers to testing for individuals at risk of HIV infection. HIV self-sampling (HIVSS) was available previously to self-testing but was confined mainly to the USA and the UK. It remains to be seen whether the momentum behind HIVST will also energise efforts to expand HIVSS. Recent years have seen a rapid growth in the type of evidence related to these interventions as well as several systematic reviews. The vast majority of this evidence relates to acceptability as well as values and preferences, although new types of evidence are emerging. This systematic map aims to consolidate all emerging evidence related to HIVST and HIVSS to respond to this rapidly changing area. METHODS: We will systematically search databases and the abstracts of five conferences from 2006 to the present date, with monthly-automated database searches. Searches will combine key terms relating to HIV (e.g. HIV, AIDS, human immune-deficiency syndrome) with terms related to self-testing (e.g. home-test, self-test, mail-test, home dried blood spot test). Abstracts will be reviewed against inclusion criteria in duplicate. Data will be manually extracted through a standard form and then entered to an open access relational map (HIVST.org). When new and sufficient evidence emerges which addresses existing knowledge gaps, we will complete a review on a relevant topic. DISCUSSION: This innovative approach will allow rapid cataloguing, documenting and dissemination of new evidence and key findings as they emerge into the public domain. SYSTEMATIC REVIEW REGISTRATION: This protocol has not been registered with PROSPERO as they do not register systematic maps

HIV self-testing intervention experiences and kit usability: results from a qualitative study among men who have sex with men in the SELPHI (Self-Testing Public Health Intervention) randomized controlled trial in England and Wales.

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes

Pilot phase of an internet-based RCT of HIVST targeting MSM and transgender people in England and Wales: advertising strategies and acceptability of the intervention

BACKGROUND: The SELPHI study (An HIV Self-Testing Public Health Intervention) is an online randomised controlled trial (RCT) of HIV self-testing (HIVST). The aim of this study was to assess the feasibility of recruiting UK men who have sex with men (cis and trans) and trans women who have sex with men to the SELPHI pilot, and the acceptability of the HIVST intervention used among those randomised to receive a kit. METHODS: A mixed-methods approach to assessing trial feasibility and intervention acceptability was taken, using quantitative data from advertising sources and RCT surveys alongside qualitative data from a nested sub-study. RESULTS: Online recruitment and intervention delivery was feasible. The recruitment strategy led to the registration of 1370 participants of whom 76% (1035) successfully enrolled and were randomised 60/40 to baseline testing vs no baseline testing. Advertising platforms performed variably. Reported HIVST kit use increased from 83% at two weeks to 96% at three months. Acceptability was very high across all quantitative measures. Participants described the instructions as easy to use, and the testing process as simple. The support structures in SELPHI were felt to be adequate. Described emotional responses to HIVST varied. CONCLUSIONS: Recruiting to a modest sized HIVST pilot RCT is feasible, and the recruitment, intervention and HIVST kit were acceptable. Research on support needs of individuals with reactive results is warranted

Sexual risk and HIV testing disconnect in men who have sex with men (MSM) recruited to an online HIV self-testing trial.

OBJECTIVES: We report the frequency of previous HIV testing at baseline in men who have sex with men (MSM) who enrolled in an HIV self-testing (HIVST) randomized controlled trial [an HIV self-testing public health intervention (SELPHI)]. METHODS: Criteria for enrolment were age ≥ 16 years, being a man (including trans men) who ever had anal intercourse (AI) with a man, not being known to be HIV positive and having consented to national HIV database linkage. Using online survey baseline data (2017-2018), we assessed associations with never having tested for HIV and not testing in the previous 6 months, among men who reported at least two recent condomless AI (CAI) partners. RESULTS: A total of 10 111 men were randomized; the median age was 33 years [interquartile range (IQR) 26-44 years], 89% were white, 20% were born outside the UK, 0.8% were trans men, 47% were degree educated, and 8% and 4% had ever used and were currently using pre-exposure prophylaxis (PrEP), respectively. In the previous 3 months, 89% reported AI and 72% reported CAI with at least one male partner. Overall, 17%, 33%, 54%, and 72% had tested for HIV in the last 3 months, 6 months, 12 months and 2 years, respectively; 13% had tested more than 2 years ago and 15% had never tested. Among 3972 men reporting at least two recent CAI partners, only 22% had tested in the previous 3 months. Region of residence and education level were independently associated with recent HIV testing. Among current PrEP users, 15% had not tested in the previous 6 months. CONCLUSIONS: Most men in SELPHI, particularly those reporting at least two CAI partners and current PrEP users, were not testing in line with current UK recommendations. The results of the trial will inform whether online promotion of HIVST addresses ongoing testing barriers

Optimized Dynamical Decoupling in a Model Quantum Memory

We present experimental measurements on a model quantum system that demonstrate our ability to dramatically suppress qubit error rates by the application of optimized dynamical decoupling pulse sequences in a variety of experimentally relevant noise environments. We provide the first demonstration of an analytically derived pulse sequence developed by Uhrig, and find novel sequences through active, real-time experimental feedback. These new sequences are specially tailored to maximize error suppression without the need for a priori knowledge of the ambient noise environment. We compare these sequences against the Uhrig sequence, and the well established CPMG-style spin echo, demonstrating that our locally optimized pulse sequences outperform all others under test. Numerical simulations show that our locally optimized pulse sequences are capable of suppressing errors by orders of magnitude over other existing sequences. Our work includes the extension of a treatment to predict qubit decoherence under realistic conditions, including the use of finite-duration, square $\pi$ pulses, yielding strong agreement between experimental data and theory for arbitrary pulse sequences. These results demonstrate the robustness of qubit memory error suppression through dynamical decoupling techniques across a variety of qubit technologies.Comment: Subject to press embarg

An enigmatic hypoplastic defect of the maxillary lateral incisor in recent and fossil orangutans from Sumatra (Pongo abelii) and Borneo (Pongo pygmaeus)

Developmental dental pathologies provide insight into health of primates during ontogeny, and are particularly useful for elucidating the environment in which extant and extinct primates matured. Our aim is to evaluate whether the prevalence of an unusual dental defect on the mesiolabial enamel of the upper lateral incisor, thought to reflect dental crowding during maturation, is lesser in female orangutans, with their smaller teeth, than in males; and in Sumatran orangutans, from more optimal developmental habitats, than in those from Borneo. Our sample includes 49 Pongo pygmaeus (87 teeth), 21 P. abelii (38 teeth), Late Pleistocene paleo-orangutans from Sumatra and Vietnam (67 teeth), Late Miocene catarrhines Lufengpithecus lufengensis (2 teeth), and Anapithecus hernyaki (7 teeth). Methods include micro-CT scans, radiography, and dental metrics of anterior teeth. We observed fenestration between incisor crypts and marked crowding of unerupted crowns, which could allow tooth-to-tooth contact. Tooth size does not differ significantly in animals with or without the defect, implicating undergrowth of the jaw as the proximate cause of dental crowding and defect presence. Male orangutans from both islands show more defects than do females. The defect is significantly more common in Bornean orangutans (71 %) compared to Sumatran (29 %). Prevalence among fossil forms falls between these extremes, except that all five individual Anapithecus show one or both incisors with the defect. We conclude that maxillary lateral incisor defect is a common developmental pathology of apes that is minimized in optimal habitats and that such evidence can be used to infer habitat quality in extant and fossil apes

Rubisco evolution in C₄ eudicots: an analysis of Amaranthaceae sensu lato.

BACKGROUND: Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) catalyses the key reaction in the photosynthetic assimilation of CO₂. In C₄ plants CO₂ is supplied to Rubisco by an auxiliary CO₂-concentrating pathway that helps to maximize the carboxylase activity of the enzyme while suppressing its oxygenase activity. As a consequence, C₄ Rubisco exhibits a higher maximum velocity but lower substrate specificity compared with the C₃ enzyme. Specific amino-acids in Rubisco are associated with C₄ photosynthesis in monocots, but it is not known whether selection has acted on Rubisco in a similar way in eudicots. METHODOLOGY/PRINCIPAL FINDINGS: We investigated Rubisco evolution in Amaranthaceae sensu lato (including Chenopodiaceae), the third-largest family of C₄ plants, using phylogeny-based maximum likelihood and Bayesian methods to detect Darwinian selection on the chloroplast rbcL gene in a sample of 179 species. Two Rubisco residues, 281 and 309, were found to be under positive selection in C₄ Amaranthaceae with multiple parallel replacements of alanine by serine at position 281 and methionine by isoleucine at position 309. Remarkably, both amino-acids have been detected in other C₄ plant groups, such as C₄ monocots, illustrating a striking parallelism in molecular evolution. CONCLUSIONS/SIGNIFICANCE: Our findings illustrate how simple genetic changes can contribute to the evolution of photosynthesis and strengthen the hypothesis that parallel amino-acid replacements are associated with adaptive changes in Rubisco