How can HIV self-testing facilitate increased access to HIV testing among multiply marginalised populations? Perspectives from GBMSM and trans women in England and Wales.

BACKGROUND: HIV self-testing (HIVST) may facilitate marginalised populations' uptake of HIV testing, but whether the extent of marginalisation challenges individual uptake of HIVST remains under-researched. We aim to explore the perspectives of multiply marginalised cis-gender gay, bisexual and other men who have sex with men (GBMSM) and trans women on whether HIVST might increase their uptake of HIV testing. METHODS: We reanalysed qualitative interview data from SELPHI (the UK's largest HIVST randomised trial) collected between 2017 and 2020 from marginalised populations, defined as people self-identifying as non-heterosexual, transgender, non-White ethnicity and/or with low educational attainment. Thirty-eight interviews with multiply marginalised individuals were thematically examined using the framework method. We specifically focussed on kit usability (a function of the interaction between blood-based HIVST kits and users), perspectives on how HIVST can improve access to HIV testing and suggestions on need-based scale-up of HIVST. RESULTS: HIVST kits were considered usable and acceptable by multiply marginalised GBMSM and trans women. The majority of interviewees highlighted multi-levelled barriers to accessing HIV testing services due to structural and social marginalisation. Their multiply marginalised identities did not impede HIVST uptake but often form motivation to self-test. Three potential roles of HIVST in the HIV testing landscape were identified: (1) alternation of HIVST and facility-based testing, (2) integration of HIVST into sexual health services and (3) substituting facility-based testing with HIVST in the future. Perceived beneficiaries of HIVST included trans communities, individuals with undisclosed sexuality and people with physical disabilities. DISCUSSION: HIVST can facilitate marginalised populations' access and uptake of HIV testing by alternating with, integrating into and substituting for facility-based services in the UK. Marginalised identities did not present challenges but rather opportunities for person-centred scale-up of HIVST. Future implementation programmes should ensure equitable access to HIVST among trans people, men unable to disclose their sexuality, and perhaps people with physical disabilities.

Needs & networks: understanding the role and impact of social networks on HIV (self-)testing among GBMSM and trans people in England and Wales.

BACKGROUND: Understanding how HIV self-testing (HIVST) can meet the testing needs of gay, bisexual and other men who have sex with men (GBMSM) and trans people whose social networks vary is key to upscaling HIVST implementation. We aim to develop a contextual understanding of social networks and HIV testing needs among GBMSM (cis and transgender) and trans women in SELPHI (An HIV Self-testing Public Health Intervention), the UK's largest randomised trial on HIVST. METHODS: This study re-analysed qualitative interviews conducted from 2015 to 2020. Forty-three in-person interviews were thematically analysed using the Framework Method. Our analytic matrix inductively categorised participants based on the unmet needs for HIV testing and the extent of social network support. The role of social networks on HIVST behaviour was explored based on individuals' testing trajectories. RESULTS: Four distinct groups were identified based on their unmet testing needs and perceived support from social networks. Optimisation advocates (people with high unmet needs and with high network support, n = 17) strived to tackle their remaining barriers to HIV testing through timely support and empowerment from social networks. Privacy seekers (people with high unmet needs and with low network support, n = 6) prioritised privacy because of perceived stigma. Opportunistic adopters (people with low unmet needs and with high network support, n = 16) appreciated social network support and acknowledged socially privileged lives. Resilient testers (people with low unmet needs and with low network support, n = 4) might hold potentially disproportionate confidence in managing HIV risks without sustainable coping strategies for potential seroconversion. Supportive social networks can facilitate users' uptake of HIVST by: (1) increasing awareness and positive attitudes towards HIVST, (2) facilitating users' initiation into HIVST with timely support and (3) affording participants an inclusive space to share and discuss testing strategies. CONCLUSIONS: Our proposed categorisation may facilitate the development of differentiated person-centred HIVST programmes. HIVST implementers should carefully consider individuals' unmet testing needs and perceived levels of social support, and design context-specific HIVST strategies that link people lacking supportive social networks to comprehensive HIV care.

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.

Differentiating impacts of non-pharmaceutical interventions on non-coronavirus disease-2019 respiratory viral infections: Hospital-based retrospective observational study in Taiwan.

BACKGROUND: Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease-2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored. METHODS: This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January-December 2019) to post-COVID period (January-May 2020). Patients with respiratory syndromes were tested for both enveloped (eg, influenza virus and seasonal coronavirus) and non-enveloped RVs (eg, enterovirus and rhinovirus) using multiplex reverse transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods. RESULTS: A total of 9693 patients underwent 12 127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan's national notification database. CONCLUSIONS: Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Health authorities may consider using hydrogen peroxide or chloride-based disinfectants as additional preventative strategies against non-enveloped respiratory viruses in the post-COVID-19 era.

Social consequences of mass quarantine during epidemics: a systematic review with implications for the COVID-19 response.

Four billion people worldwide have experienced coronavirus disease 2019 (COVID-19) confinement. Such unprecedented extent of mobility restriction to curb the COVID-19 pandemic may have profound impacts on how individuals live, travel and retain well-being. This systematic review aims to identify (i) the social consequences of mass quarantine-community-wide movement restrictions-during previous and current infectious disease outbreaks and (ii) recommended strategies to mitigate the negative social implications of COVID-19 lockdowns. Considering social determinants of health, we conducted a systematic review by searching five databases (Ovid-MEDLINE, EMBASE, PsycINFO, China National Knowledge Infrastructure and the World Health Organization COVID-19 database) for publications from inception to 9 April 2020. No limitation was set on language, location or study type. Studies that (i) contained peer-reviewed original empirical evidence and (ii) focussed on non-epidemiological implications of mass quarantine were included. We thematically synthesized and reported data due to heterogeneous disease and country context. Of 3067 publications found, 15 original peer-reviewed articles were selected for full-text extraction. Psychological distress, heightened communication inequalities, food insecurity, economic challenges, diminished access to health care, alternative delivery of education and gender-based violence were identified as negative social consequences of community-based quarantine in six infectious disease epidemics, including the current COVID-19 pandemic. In contrast, altruistic attitudes were identified as a positive consequence during previous quarantines. Diverse psychological and social consequences of mass quarantine in previous and current epidemics were evident, but individual country policies had been highly varied in how well they addressed the needs of affected individuals, especially those who are socially marginalized. Policymakers should balance the pros and cons of movement restrictions, facilitate multisectoral action to tackle social inequalities, provide clear and coherent guidance to the public and undertake time-bound policy evaluations to mitigate the negative impact of COVID-19 lockdowns and to establish preparedness strategies for future epidemics.

Taiwan guideline on oral pre-exposure prophylaxis for HIV prevention - 2018 update.

Pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus infection is proved to be effective and has been implemented worldwide. This article introduces the guideline development and revised recommendations and guidance on PrEP provision in the updated Taiwan PrEP guideline. The Taiwan PrEP guideline writing group searched randomized controlled trials and guidelines published before October 2017 through Medline/PubMed, Cochrane Database, Embase and ClinicalTrials.gov database. Keywords included pre(-)exposure prophylaxis, PrEP, Truvada, tenofovir, HIV, and AIDS. Each selected article was assessed by two authors using the Grading of Recommendations Assessment, Development and Evaluation. External reviewers were invited to independently evaluate the revised manuscript per the Appraisal of Guidelines for Research and Evaluation II. Before publication, a public consultation was held to reach consensus on the updated guideline among providers, civil society, and Taiwan Centers for Disease Control. Four systematic reviews and 28 original articles were reviewed by Taiwan PrEP writing group. The second version of the Taiwan PrEP guideline was released in March 2018. We recommended daily PrEP use for the following populations: strong recommendation and high quality of evidence for men who have sex with men (MSM) and transgender women (TGW), as well as heterosexual serodiscordant couples; weak recommendation and high quality of evidence for people who inject drugs, while weak recommendation and moderate quality of evidence for at-risk heterosexual men and women. There is high-quality evidence for event-driven PrEP in MSM and likely TGW, and we additionally recognized these key populations could benefit from such dosing regimen.

Prone position is associated with mild cerebral oxygen desaturation in elderly surgical patients.

PURPOSE: A variety of hemodynamic and respiratory alterations accompany patients in the prone position; however the effect of the prone position on intraoperative cerebral saturation has not been studied. We sought to examine whether the incidence of cerebral oxygen desaturation in elderly patients (≥68 years of age) undergoing spine surgery in the prone position was more common than patients undergoing major surgery in the supine position. METHODS: We performed a retrospective cohort study of 205 patients; 63 patients underwent surgery in the prone position and 142 in the supine position. Patients were evaluated for cerebral desaturation with bilateral cerebral oximetry. The primary predictor was position, secondary were: length of the surgery, incidence and duration of cerebral desaturation episodes at several thresholds, average time of Bispectral index below threshold of 45 in minutes, average electroencephalogram suppression ratio >0, amount of blood transfused, and the incidence of hypotension and hypertension. RESULTS: Elderly spine surgery patients in the prone position were more than twice as likely to experience mild cerebral desaturation as patients in the supine position. Patients in the prone position had longer surgeries; however cerebral desaturation in the prone position was significantly more common even when adjusted for surgery time and the occurrence of intraoperative hypotension. CONCLUSION: Cerebral desaturation is related to the prone position in elderly surgery patients. Future studies are necessary to determine whether this translates to a higher incidence of postoperative cognitive dysfunction and delirium.

Cutting edge: FADD is not required for antigen receptor-mediated NF-kappaB activation.

Recently, it has been demonstrated that stimulated T cells bearing defects in caspase-8 fail to promote nuclear shuttling of NF-kappaB complexes. Such cells display strikingly similar proliferative and survival defects as T cells lacking Fas-associated death domain protein (FADD) function. We characterized NF-kappaB signaling in T cells bearing a dominant-negative FADD transgene (FADDdd). Whereas FADDdd T cells displayed proliferative defects following activation, these were not a consequence of aberrant NF-kappaB signaling, as measured by IKK/IkappaB phosphorylation and IkappaB degradation. There were no appreciable defects in nuclear translocation of p65/Rel using ImageStream, a flow-based imaging cytometer. Pretreatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a potent caspase inhibitor, also failed to impede canonical NF-kappaB signaling. Secretion of IL-2 and up-regulation of various activation markers occurred normally. Thus, FADD does not play an essential role in NF-kappaB activation, suggesting an alternative route by which this adaptor promotes the clonal expansion of T cells.

The requirements for Fas-associated death domain signaling in mature T cell activation and survival.

Fas-associated death domain (FADD) is a death domain containing cytoplasmic adapter molecule required for the induction of apoptosis by death receptors. Paradoxically, FADD also plays a crucial role in the development and proliferation of T cells. Using T cells from mice expressing a dominant negative form of FADD (FADDdd), activation with anti-TCR Ab and costimulation or exogenous cytokines is profoundly diminished. This is also seen in wild-type primary T cells transduced with the same transgene, demonstrating that FADD signaling is required in normally differentiated T cells. The defective proliferation does not appear to be related to the early events associated with TCR stimulation. Rather, with a block in FADD signaling, stimulated T cells exhibit a high rate of cell death corresponding to the initiation of cell division. Although CD4 T cells exhibit a moderate deficiency, this effect is most profound in CD8 T cells. In vivo, the extent of this defective accumulation is most apparent; lymphocytic choriomenigitis virus-infected FADDdd-expressing mice completely fail to mount an Ag-specific response. These results show that, in a highly regulated fashion, FADD, and most likely caspases, can transduce either a signal for survival or one that leads directly to apoptosis and that the balance between these opposing outcomes is crucial to adaptive immunity.