The HepHIV 2023 Madrid conference: A call to action for political leadership in reaching the sustainable development goals on earlier testing and linkage to care for HIV, viral hepatitis, and sexually transmitted infections.

INTRODUCTION AND OBJECTIVES: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union. METHODS: The HepHIV 2023 organizing committee, alongside the Spanish Ministry of Health, oversaw the conference organization and prepared the scientific programme based on abstract rankings. Key outcomes are derived from conference presentations and discussions. RESULTS: Conference presentations covered the obstacles that HIV-related stigma and discrimination continue to pose to access to services, models for data collection to better monitor progress in the future, and examples of legislative action that can be taken at national levels. Diversification of testing approaches was also highlighted, to reach key populations, (e.g. migrant populations), to increase testing offered in healthcare settings (e.g. emergency departments), and to account for different stages of epidemics across the region. CONCLUSION: With a strong call for intensified action to address the impact of HIV-related stigma and discrimination on testing uptake, the conference concluded that strengthened collaboration is required between governments and implementers around testing and linkage to care. There is also an ongoing need to ensure sustainable political commitment and appropriate resource allocation to address gaps and inequalities in access for key populations and to focus on the implementation of integrated responses to HIV, viral hepatitis, and sexually transmitted infections.

Impact of national commissioning of pre-exposure prophylaxis (PrEP) on equity of access in England: a PrEP-to-need ratio investigation.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. In England, NHS availability was limited to participants of the PrEP Impact Trial until late 2020. Some key populations at greater risk of HIV were under-represented in the trial suggesting inequities in trial PrEP access. We used the PrEP-to-need ratio (PnR; number of PrEP users divided by new HIV diagnoses) to investigate whether PrEP access improved following routine commissioning in October 2020 and identify populations most underserved by PrEP. METHODS: Aggregated numbers of people receiving ≥1 PrEP prescription and non-late new HIV diagnoses (epidemiological proxy for PrEP need) were taken from national surveillance data sets. We calculated the PnR across socio-demographics during Impact (October 2017 to February 2020; pre-COVID-19 pandemic) and post-commissioning PrEP era (2021) in England. RESULTS: PnR increased >11 fold, from 4.2 precommissioning to 48.9 in 2021, due to a fourfold reduction in non-late new HIV diagnoses and near threefold increase in PrEP users. PnR increased across genders, however, the men's PnR increased 12-fold (from 5.4 precommissioning to 63.9 postcommissioning) while the women's increased sevenfold (0.5 to 3.5). This increasing gender-based inequity was observed across age, ethnicity and region of residence: white men had the highest PnR, increasing >13 fold (7.1 to 96.0), while Black African women consistently had the lowest PnR, only increasing slightly (0.1 to 0.3) postcommissioning, suggesting they were the most underserved group. Precommissioning, the PnR was 78-fold higher among white men than Black women, increasing to 278-fold postcommissioning. CONCLUSIONS: Despite the overall increase in PrEP use, substantial PrEP Impact trial inequities widened postcommissioning in England, particularly across gender, ethnicity and region of residence. This study emphasises the need to guide HIV combination prevention based on equity metrics relative to the HIV epidemic. The PnR could support the optimisation of combination prevention to achieve zero new HIV infections in England by 2030.

Acceptability of Dyad Care Management After Preterm Birth: A Qualitative Study.

OBJECTIVES: Care management programs for medically complex infants interact with parents after complicated pregnancies, when gaps in maternal health care are well documented. These care managers may have the relationships and skills to promote postpartum and interconception health and health care access. It is unknown whether expanding these care management models to address maternal needs would be acceptable. METHODS: We conducted qualitative interviews with women with a history of preterm birth and clinicians. For women with a history of preterm birth, additional inclusion criteria were Medicaid-insured infant in one health system and English proficiency. We purposively oversampled women whose infants received care management. Clinicians worked in two geographically adjacent health systems. Interviews explored priorities after preterm birth and perceived acceptability of mother-infant dyad care management. Interviews were audio recorded, transcribed, and coded following an integrated approach in which we applied a priori codes and captured emergent themes. RESULTS: We interviewed 33 women (10/2018-7/2021) and 24 clinicians (3/2021-8/2021). Women were predominantly non-Hispanic Black, and 15 had infants receiving care management. Clinicians included physicians, nurses, and social workers from Pediatrics, Obstetrics, and Family Medicine. Subgroups converged thematically, finding care management acceptable. Tailoring programs to address stress and sleep, emphasizing care managers with strong interpersonal skills and shared experiences with care management users, and program flexibility would contribute to acceptability. CONCLUSIONS FOR PRACTICE: Dyad care management after preterm birth is acceptable to potential program end-users and clinicians. Dyad health promotion may contribute to improved birth outcomes, infant, and parent health.

"Sex without fear": exploring the psychosocial impact of oral HIV pre-exposure prophylaxis on gay men in England.

Gay, bisexual, and other men who have sex with men (GBMSM) experience a high prevalence of psychosocial health problems, such as harmful substance use and depression, as well as being disproportionately affected by HIV. HIV Pre-Exposure Prophylaxis (PrEP) may provide psychosocial benefits beyond its intended purpose of reducing HIV infection. We explore the psychosocial impact of oral PrEP use on gay men in England using qualitative data from the PROUD study. From February 2014 to January 2016, semi-structured in-depth interviews were conducted with 40 gay men and one trans woman. Participants were purposively recruited based on trial arm allocation, adherence, and sexual risk behaviours. By removing HIV risk from sex, PrEP improves users' wellbeing by reducing HIV-related anxiety and internalised stigma and increasing HIV prevention self-efficacy, sexual pleasure, and intimacy. In turn, these psychological changes may influence behaviour in the form of greater sexual freedom, reduced harmful drug use, and more protective sexual health behaviours. However, PrEP may create internal conflict for some gay men, due to its disruption of social norms around condom use and its perceived influence on their sexual behaviour leading to reduced condom self-efficacy. These findings provide a baseline of PrEP's psychosocial impact amongst some of the first PrEP users in England and supports calls to consider the psychosocial impact of PrEP in prescribing guidelines.

Follicle-stimulating hormone in postmenopausal women living with HIV: a prevalence study.

OBJECTIVES: We examined follicle-stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months' amenorrhoea, and investigated correlation with menopausal symptoms. METHODS: A cross-sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months' amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal-Wallis test. RESULTS: Median age was 53 years [interquartile range (IQR): 51-55]; all were on antiretroviral therapy, three-quarters (n = 65) had a CD4 T-cell count > 500 cells/µL and 91.8% (n = 78) had an HIV viral load (VL) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1-78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T-cell count ≥ 200 cells/µL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m2 ). Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37). CONCLUSIONS: Four women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2 . We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months' amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.

Late diagnosis of HIV: An updated consensus definition.

INTRODUCTION: In recent years, HIV testing frequency has increased, resulting in more people being diagnosed during seroconversion with a temporarily low CD4 count. Using the current consensus definition of late HIV presentation ('presenting for care with a CD4 count < 350 cells/µL or an AIDS-defining event, regardless of CD4 count') these individuals would be incorrectly assigned as being diagnosed late. METHODS: In spring 2022, a European expert group convened to revise the current late HIV presentation consensus definition. A survey on data availability to apply this revised definition was sent to nominated European focal points responsible for HIV surveillance (n = 53). RESULTS: Experts agreed that the updated definition should refer to late HIV diagnosis rather than presentation and include the following addition: People with evidence of recent infection should be reclassified as 'not late', with evidence of recent infection considered hierarchically. The individual must have: (i) laboratory evidence of recent infection; (ii) a last negative HIV test within 12 months of diagnosis; or (iii) clinical evidence of acute infection. People with evidence of being previously diagnosed abroad should be excluded. A total of 18 countries responded to the survey; 83% reported capturing CD4 count and/or AIDS at diagnosis through national surveillance, 67% captured last negative test and/or previous HIV diagnosis, 61% captured seroconversion illness at diagnosis and 28% captured incident antibody results. CONCLUSIONS: Accurate data on late diagnosis are important to describe the effects of testing programmes. Reclassification of individuals with recent infection will help to better identify populations most at risk of poor HIV outcomes and areas for intervention.

COVID-19 mortality among people with diagnosed HIV compared to those without during the first wave of the COVID-19 pandemic in England.

OBJECTIVES: We describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England. METHODS: National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID-19 mortality surveillance data (2 March 2020-16 June 2020); HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID-19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity. RESULTS: Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID-19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID-19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15-59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID-19 mortality risk than those without (2.18; 95% CI: 1.76-2.70). Most people with HIV who died of/with COVID-19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID-19 outcomes (87%). CONCLUSIONS: In the first wave of the pandemic in England, COVID-19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID-19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity.

Perceptions and Practicalities Influencing Pre-exposure Prophylaxis Adherence Among Men Who Have Sex with Men in England.

PrEP is highly effective for HIV prevention but requires adequate adherence. In this paper we use the perceptions and practicalities approach (PAPA) to identify factors that influenced PrEP adherence using qualitative data from the PROUD study. From February 2014 to January 2016, we interviewed 41 gay, bisexual and other men-who-have-sex-with-men and one trans woman who were enrolled in the study. We purposively recruited participants for interview based on trial arm allocation, adherence and sexual risk behaviours. The interviews were conducted in English, audio-recorded, transcribed, coded and analysed using framework analysis. Participants in general were highly motivated to use and adhere to PrEP, and this was linked to strong perceptions of personal necessity for PrEP as they felt at risk of HIV and viewed PrEP as highly effective. On the other hand, concerns about side effects and HIV resistance did inhibit PrEP initiation and adherence although this was uncommon. Practical factors such as daily routine, existing habitual pill-taking and pill storage impacted adherence. Drug and alcohol use rarely caused participants to miss doses. These findings indicate that using the principals of PAPA to unpick influencers of PrEP use, could help tailor adherence support in PrEP programmes.

National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review.

BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Why sexual health clinics are important in the 2020s.

To make services more accessible, acceptable and affordable, sexual health service delivery models have embraced innovation, technology, outreach and decentralisation. In particular, some routine high-volume services, like asymptomatic testing for sexually transmitted infections (STIs), can be delivered in general practice, online or in non-clinical settings. On the surface, sexual health clinics, like hospitals or other primary care clinics, might appear to be operating on a model that has not changed significantly in recent times. However, globally sexual healthcare needs are rising both in volume and complexity, not all of which can be adequately met through decentralised care. Sexual health clinics themselves are the site of considerable innovation. The importance of sexual health clinics in the diagnosis and treatment of symptomatic STIs is likely to increase with the increasing burden of disease, the complexity of treatment guidelines and the emergence of new infections. Services essential to patient health such as immediate or complex clinical care, partner notification and safeguarding, and activities essential to the health system like research, training and supervision require expertise to be located where it can be accessed and maintained at reasonable cost. We do not know whether increasing some services outside existing models can safely compensate for reducing other services inside them.

Menopausal status, age and management among women living with HIV in the UK.

BACKGROUND: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45-60 years in England. METHODS: Socio-demographic, lifestyle and clinical data were collected through a self-completed cross-sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre-, peri- or post-menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan-Meier survival analysis. RESULTS: The 847 women had a median age of 49 [interquartile range (IQR): 47-52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre-, peri- or post-menopausal, respectively. After adjusting for age, associations of menopausal status with non-cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43-0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20-5.94)] and unemployment [1.34 (0.97-1.84)] remained significant. Median (IQR) age at LMP was 54 (51-55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. CONCLUSIONS: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options.

HIV seroprevalence in five key populations in Europe: a systematic literature review, 2009 to 2019.

BackgroundIn Europe, HIV disproportionately affects men who have sex with men (MSM), people who inject drugs (PWID), prisoners, sex workers, and transgender people. Epidemiological data are primarily available from national HIV case surveillance systems that rarely capture information on sex work, gender identity or imprisonment. Surveillance of HIV prevalence in key populations often occurs as independent studies with no established mechanism for collating such information at the European level.AimWe assessed HIV prevalence in MSM, PWID, prisoners, sex workers, and transgender people in the 30 European Union/European Economic Area countries and the United Kingdom.MethodsWe conducted a systematic literature review of peer-reviewed studies published during 2009-19, by searching PubMed, Embase and the Cochrane Library. Data are presented in forest plots by country, as simple prevalence or pooled across multiple studies.ResultsEighty-seven country- and population-specific studies were identified from 23 countries. The highest number of studies, and the largest variation in HIV prevalence, were identified for MSM, ranging from 2.4-29.0% (19 countries) and PWID, from 0.0-59.5% (13 countries). Prevalence ranged from 0.0-15.6% in prisoners (nine countries), 1.1-8.5% in sex workers (five countries) and was 10.9% in transgender people (one country). Individuals belonging to several key population groups had higher prevalence.ConclusionThis review demonstrates that HIV prevalence is highly diverse across population groups and countries. People belonging to multiple key population groups are particularly vulnerable; however, more studies are needed, particularly for sex workers, transgender people and people with multiple risks.

Association of HIV status with sexual function in women aged 45-60 in England: results from two national surveys.

Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV.

Investigating the decline in Lymphogranuloma venereum diagnoses in men who have sex with men in the United Kingdom since 2016: an analysis of surveillance data.

Background Following an upward trajectory in Lymphogranuloma venereum (LGV) diagnoses in the UK from 2004 to 2016, with annual diagnoses increasing from 28 to 904, diagnoses fell to 641 in 2017; this was inconsistent with the upward trend in other bacterial sexually transmissible infections (STIs) between 2016 and 2017. An analysis of surveillance data from multiple sources to investigate the possible factors contributing to this decline in LGV was performed. METHODS: LGV tests and diagnoses in the UK from 2004 to 2018 were captured through laboratory data from the LGV Reference Laboratories and laboratories conducting in-house LGV testing. These data and clinical diagnoses data from England were analysed alongside the national management guidelines issued over the course of the epidemic. RESULTS: LGV diagnoses increased between 2004 and 2015 and then decreased between 2016 and 2018. LGV testing increased from 2010 to 2018 (2690-10850). Test positivity halved between 2015 (14.8%, 929-6272) and 2018 (7.3%, 791-10850). Peaks in LGV testing and diagnoses appeared to coincide with the publication of national LGV management guidelines and changes to clinical practice. The proportion of LGV diagnoses among HIV-positive men who have sex with men (MSM) fell between 2013 and 2018 (74-48%). CONCLUSIONS: The fall in diagnoses and positivity were likely due to increasing earlier clinical diagnosis and treatment. Changes to the national management guidelines, the clinical policy and practice of some larger clinics and potentially changes to the guidelines for the treatment of chlamydia broadened the scope of testing and increased testing in asymptomatic patients which, in combination, likely had a positive effect on the control of LGV infection.

Nurse practitioner student clinical placement processes: A national survey of nurse practitioner programs.

BACKGROUND: Providing quality clinical sites and preceptors is one of the greatest challenges for nurse practitioner programs. PURPOSE: To conduct a national survey of nurse practitioner (NP) program directors to better understand the complex process for clinical site placement in the United States. METHODS: In 2018, a web-based survey was sent to program directors to ascertain the faculty and staff effort allocation and processes related to NP student placements, the number of required clinical rotations, the total hour requirement, and preceptor incentives and barriers. FINDINGS: There was a 47% survey response rate. Variation in processes was found across NP programs. Almost 14% of respondents said that students were required to find sites entirely on their own. Ten percent of faculty reported devoting 90% to 100% of their effort to finding preceptors. Preceptors and sites were rarely paid, but other incentives were common. DISCUSSION: It is vital for NP programs to streamline clinical placement processes, to foster academic-practice partnerships, and to advocate for federal funding to train the future NP workforce.

Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial.

BACKGROUND: B cells produce alloantibodies and activate alloreactive T cells, negatively affecting kidney transplant survival. By contrast, regulatory B cells are associated with transplant tolerance. Immunotherapies are needed that inhibit B-cell effector function, including antibody secretion, while sparing regulators and minimising infection risk. B lymphocyte stimulator (BLyS) is a cytokine that promotes B-cell activation and has not previously been targeted in kidney transplant recipients. We aimed to determine the safety and activity of an anti-BLyS antibody, belimumab, in addition to standard-of-care immunosuppression in adult kidney transplant recipients. We used an experimental medicine study design with multiple secondary and exploratory endpoints to gain further insight into the effect of belimumab on the generation of de-novo IgG and on the regulatory B-cell compartment. METHODS: We undertook a double-blind, randomised, placebo-controlled phase 2 trial of belimumab, in addition to standard-of-care immunosuppression (basiliximab, mycophenolate mofetil, tacrolimus, and prednisolone) at two centres, Addenbrooke's Hospital, Cambridge, UK, and Guy's and St Thomas' Hospital, London, UK. Participants were eligible if they were aged 18-75 years and receiving a kidney transplant and were planned to receive standard-of-care immunosuppression. Participants were randomly assigned (1:1) to receive either intravenous belimumab 10 mg per kg bodyweight or placebo, given at day 0, 14, and 28, and then every 4 weeks for a total of seven infusions. The co-primary endpoints were safety and change in the concentration of naive B cells from baseline to week 24, both of which were analysed in all patients who received a transplant and at least one dose of drug or placebo (the modified intention-to-treat [mITT] population). This trial has been completed and is registered with ClinicalTrials.gov, NCT01536379, and EudraCT, 2011-006215-56. FINDINGS: Between Sept 13, 2013, and Feb 8, 2015, of 303 patients assessed for eligibility, 28 kidney transplant recipients were randomly assigned to receive belimumab (n=14) or placebo (n=14). 25 patients (12 [86%] patients assigned to the belimumab group and 13 [93%] patients assigned to the placebo group) received a transplant and were included in the mITT population. We observed similar proportions of adverse events in the belimumab and placebo groups, including serious infections (one [8%] of 12 in the belimumab group and five [38%] of 13 in the placebo group during the 6-month on-treatment phase; and none in the belimumab group and two [15%] in the placebo group during the 6-month follow-up). In the on-treatment phase, one patient in the placebo group died because of fatal myocardial infarction and acute cardiac failure. The co-primary endpoint of a reduction in naive B cells from baseline to week 24 was not met. Treatment with belimumab did not significantly reduce the number of naive B cells from baseline to week 24 (adjusted mean difference between the belimumab and placebo treatment groups -34·4 cells per µL, 95% CI -109·5 to 40·7). INTERPRETATION: Belimumab might be a useful adjunct to standard-of-care immunosuppression in renal transplantation, with no major increased risk of infection and potential beneficial effects on humoral alloimmunity. FUNDING: GlaxoSmithKline.

Predictive factors for HIV infection among men who have sex with men and who are seeking PrEP: a secondary analysis of the PROUD trial.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) is a highly effective method of HIV prevention for men who have sex with men (MSM). However, uncertainty remains around the optimal eligibility criteria for PrEP, specifically whether there are subgroups at low risk of HIV for whom PrEP might not be warranted. METHODS: PROUD was an open-label waitlist trial design that randomised MSM attending participating sexual health centres in England to receive PrEP immediately (IMM) or after a deferral period of 1 year (DEF). This analysis is based on participants who were randomised to the deferred arm, when they did not have access to PrEP. HIV incidence was compared between subgroups defined by baseline characteristics. RESULTS: Overall, 21 participants acquired HIV infection over 239.3 person-years (PY) follow-up, yielding an incidence rate of 8.8/100 PY (95% CI 5.4 to 13.4). Two highly significant predictors for HIV acquisition were identified. Men with a self-reported diagnosis of syphilis, rectal chlamydia (CT) or rectal gonorrhoea (GC) in the previous 12 months had an incidence of 17.2/100 PY (95% CI 9.7 to 28.5); those reporting receptive anal intercourse without a condom (ncRAI) with two or more partners in the previous 3 months had an incidence of 13.6/100 PY (95% CI 7.9 to 21.7). The incidence rate among participants lacking both of these risk factors was 1.1/100 PY (1/87.6, 95% CI 0.03 to 6.4). CONCLUSIONS: The high HIV incidence in PROUD suggests that most participants appropriately judged their need for PrEP. Eligibility criteria for a PrEP programme can therefore be broad, as in the current guidelines. However, a recent history of syphilis or rectal CT/GC, or multiple ncRAI partners indicates a high imminent risk of HIV infection. MSM with any of these characteristics should be offered PrEP as a matter of urgency.

The Context of Sexual Risk Behaviour Among Men Who Have Sex with Men Seeking PrEP, and the Impact of PrEP on Sexual Behaviour.

There are still important gaps in our understanding of how people will incorporate PrEP into their existing HIV prevention strategies. In this paper, we explore how PrEP use impacted existing sexual risk behaviours and risk reduction strategies using qualitative data from the PROUD study. From February 2014 to January 2016, we conducted 41 in-depth interviews with gay, bisexual and other men who have sex with men (GBMSM) enrolled in the PROUD PrEP study at sexual health clinics in England. The interviews were conducted in English and were audio-recorded. The recordings were transcribed, coded and analysed using framework analysis. In the interviews, we explored participants' sexual behaviour before joining the study and among those using or who had used PrEP, changes to sexual behaviour after starting PrEP. Participants described the risk behaviour and management strategies before using PrEP, which included irregular condom use, sero-sorting, and strategic positioning. Participants described their sexual risk taking before initiating PrEP in the context of the sexualised use of drugs, geographical spaces linked with higher risk sexual norms, and digitised sexual networking, as well as problematic psychological factors that exacerbated risk taking. The findings highlight that in the main, individuals who were already having frequent condomless sex, added PrEP to the existing range of risk management strategies, influencing the boundaries of the 'rules' for some but not all. While approximately half the participants reduced other risk reduction strategies after starting PrEP, the other half did not alter their behaviours. PrEP provided an additional HIV prevention option to a cohort of GBMSM at high risk of HIV due to inconsistent use of other prevention options. In summary, PrEP provides a critical and necessary additional HIV prevention option that individuals can add to existing strategies in order to enhance protection, at least from HIV. As a daily pill, PrEP offers protection in the context of the sex cultures associated with sexualised drug use, digitised sexual applications and shifting social norms around sexual fulfilment and risk taking. PrEP can offer short or longer-term options for individuals as their sexual desires change over their life course offering protection from HIV during periods of heightened risk. PrEP should not be perceived or positioned in opposition to the existing HIV prevention toolkit, but rather as additive and as a tool that can and is having a substantial impact on HIV.

Intimate partner violence, depression, and sexual behaviour among gay, bisexual and other men who have sex with men in the PROUD trial.

BACKGROUND: Little is known about the prevalence and correlates of intimate partner violence (IPV) among gay, bisexual and other men who have sex with men (GBMSM) in the UK. The aim of this study was to investigate the prevalence of IPV, associations of socio-economic and psychosocial factors with IPV, and the association of IPV with depression and sexual behaviour, among GBMSM in the PROUD trial of pre-exposure prophylaxis (PrEP). METHODS: PROUD enrolled 544 HIV-negative participants in England from 2012 to 2014; participants were randomised to immediate or deferred PrEP. This analysis included 436 GBMSM who had IPV data at month-12 and/or 24. Prevalence of IPV victimization and perpetration (lifetime, and in the past year) was assessed at these time-points. Generalized estimating equations were used to investigate associations with IPV, using pooled data from both time-points. RESULTS: At month-12 (N = 410), 44.9% of men reported ever being a victim of IPV, 15.6% in the last year, and 19.5% reported ever perpetrating IPV, 7.8% in the last year. At month-24 (N = 333), the corresponding prevalence was 40.2 and 14.7% for lifetime and past year IPV victimization and 18.0 and 6.9% for lifetime and past year IPV perpetration. IPV prevalence did not differ by randomised arm. Men reporting internalized homophobia and sexualized drug use were more likely to report IPV. Lifetime and last year experience of IPV victimization and perpetration were strongly associated with depressive symptoms (PHQ-9 ≥ 10) (adjusted for socio-demographics: lifetime IPV victimization PR 2.57 [95% CI: 1.71, 3.86]; past year IPV victimization PR 2.93 [95% CI: 1.96, 4.40]; lifetime IPV perpetration PR 2.87 [95% CI: 1.91, 4.32]; past year IPV perpetration PR 3.47 [95% CI: 2.13, 5.64], p < 0.001 for all); IPV was not consistently associated with measures of condomless anal sex or high partner numbers. CONCLUSIONS: GBMSM at high-risk of HIV who are seeking/taking PrEP may experience a high burden of IPV, which may be linked to depression. Training on awareness of and enquiry for IPV among GBMSM in sexual health clinics is recommended. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02065986 . Registered 19 February 2014 (retrospectively registered).