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

Exploring Mechanisms of Action: Using a Testing Typology to Understand Intervention Performance in an HIV Self-Testing RCT in England and Wales.

SELPHI involves two interventions: (A) It provides one HIV self-testing (HIVST) kit; (B) It offers 3-monthly repeat HIVST kits if participants report ongoing risk. A logic model underpinned by the Behaviour Change Wheel informed the design of the intervention. SELPHI recruited 10,135 cis-men and trans people in England and Wales, all reporting anal sex with a man. This paper explores how the interventions were experienced and the pathways to impact for different groups of trial participants. In-depth interviews with 37 cis-men who have sex with men (MSM) were used to inductively categorise participants based on sexual and HIV testing histories. Themes relating to intervention experiences and impacts were mapped onto SELPHI-hypothesised intermediate outcomes to consider intervention impacts. Three groups were identified: 'Inexperienced testers' engaged with SELPHI to overcome motivational and social and physical opportunity testing barriers. For 'pro self-testers', testing frequency was constrained by psychological and social barriers and lack of opportunity. 'Opportunistic adopters' engaged in HIVST for novelty and convenience. Perceived impacts for inexperienced testers were most closely aligned with the logic model, but for opportunistic adopters there was little evidence of impact. Distinctive groups were discernible with divergent intervention experiences. Using COM-B as a model for understanding behaviour change in relation to HIVST, our results indicate how HIVST interventions could be adapted to respond to different needs based on the target population's demographic and behavioural features

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

Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol

Background: Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe. Methods: KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes. Discussion: Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children. Trial registration: ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17

Impact and acceptability of HIV self-testing for trans men and trans women: A mixed-methods subgroup analysis of the SELPHI randomised controlled trial and process evaluation in England and Wales.

BACKGROUND: Globally, trans people are disproportionately affected by HIV, but research on strategies to increase testing are limited. SELPHI is a randomised-controlled-trial (RCT) of 10,135 cis men, trans men, and trans women reporting lifetime anal intercourse with male partners (cis or trans), evaluating whether the offer of free HIV self-testing (HIVST) increases diagnosis. This subgroup analysis from the SELPHI RCT aims to describe key HIVST outcomes and HIVST acceptability for trans people. METHODS: SELPHI recruited using social networking and trans focused social media. Participants were randomised 60/40 to baseline HIVST (Biosure™) (BT) vs no baseline HIVST (nBT); and at 3-months (if completed the survey and reported recent CAI) 50/50 to 3-monthly HIVST (RT) vs no repeat HIVST (nRT). Outcomes were self-reported through online surveys. We conducted a qualitative study of semi-structured peer-led participant interviews (n = 20) exploring HIVST motivations and experiences. These were analysed using a framework approach. FINDINGS: SELPHI recruited and randomised 118 trans men and trans women (94 trans men, 24 trans women), of whom 20 (16 trans men, 4 trans women) underwent the second randomisation. Median age at baseline was 29 (IQR: 22, 37), 79% were white, 79% were UK born, 37% had degree level education, and 31% had never tested for HIV. 62% (n = 59) of trans men completed the 3-month survey, but survey completion by trans women in nBT was too low (1/11) for randomised comparison. In trans men HIV testing uptake by 3 months was significantly higher in BT (95% 36/38) vs nBT (29%, 6/21) (RR=3.32 (1.68, 6.55) p<0.001). Trans people randomised to RT reported 3 times higher rate of HIV testing compared to nRT during the two-year follow-up (IRR 3.66 (1.86, 8.01) p<0.0001). STI testing frequency (mean number of tests during each 13 week period/ 2-year follow-up) was not significantly different across interventions: RT (0.03) and nRT (0.01) (IRR=1.86 95%CI; 0.77, 5.15; p = 0.15). Social harms were rare. Acceptability was very high in BT: 97% (38/39) found instructions easy to understand, 97% (37/38) found the HIVST simple to use and 100% (39/39) reported good overall experience. In interviews, reported HIVST benefits included increased autonomy, privacy, convenience and avoidance of health care providers perceived to be discriminatory and services that increased dysphoria. Minor lancet and test processing issues were reported. INTERPRETATION: HIVST significantly increased testing uptake and frequency in trans men and trans people overall, although recruitment and retention of trans women was low. HIVST acceptability was high and indicates easy access to this novel technology may increase HIV testing access for this key population

Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study

Background PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design. Methods Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants. Results Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported ‘being deferred’ as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design. Conclusion The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and generally acceptable to most participants in this study

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

Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial

CONTEXT Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. OBJECTIVE To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. INTERVENTION Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. MAIN OUTCOME MEASURES The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. RESULTS There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03). CONCLUSION Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN30019040

PROMIS - Prostate MR imaging study: a paired validating cohort study evaluating the role of multi-parametric MRI in men with clinical suspicion of prostate cancer

Background: Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway. Methods: PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10-12 core TRUS-biopsy (standard) and 5. mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others. Results: PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers

Acceptability of the study data collection.

<p>Acceptability of the study data collection.</p