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

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

Recommendations for defining preventable HIV-related mortality for public health monitoring in the era of Getting to Zero: an expert consensus.

Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data. These recommendations were informed by a comprehensive literature review and agreed by 42 international experts, including clinicians, public health professionals, researchers, commissioners, and community representatives. By applying the recommendations to 2019 national HIV surveillance data from the UK, we show that 30% of deaths among people with HIV were HIV-related or possibly HIV-related, and at least 63% of these deaths were preventable or potentially preventable. The application of these recommendations by health authorities will ensure consistent monitoring of HIV elimination targets and allow for the identification of inequalities and areas for intervention.

Assessing the impact of online postal self-sampling for sexually transmitted infections on health inequalities, access to care and clinical outcomes in the UK: protocol for ASSIST, a realist evaluation.

INTRODUCTION: The past decade has seen a rapid increase in the volume and proportion of testing for sexually transmitted infections that are accessed via online postal self-sampling services in the UK. ASSIST (Assessing the impact of online postal self-sampling for sexually transmitted infections on health inequalities, access to care and clinical outcomes in the UK) aims to assess the impact of these services on health inequalities, access to care, and clinical and economic outcomes, and to identify the factors that influence the implementation and sustainability of these services. METHODS AND ANALYSIS: ASSIST is a mixed-methods, realist evaluated, national study with an in-depth focus of three case study areas (Birmingham, London and Sheffield). An impact evaluation, economic evaluation and implementation evaluation will be conducted. Findings from these evaluations will be analysed together to develop programme theories that explain the outcomes. Data collection includes quantitative data (using national, clinic based and online datasets); qualitative interviews with service users, healthcare professionals and key stakeholders; contextual observations and documentary analysis. STATA 17 and NVivo will be used to conduct the quantitative and qualitative analysis, respectively. ETHICS AND DISSEMINATION: This study has been approved by South Central - Berkshire Research Ethics Committee (ref: 21/SC/0223). All quantitative data accessed and collected will be anonymous. Participants involved with qualitative interviews will be asked for informed consent, and data collected will be anonymised.Our dissemination strategy has been developed to access and engage key audiences in a timely manner and findings will be disseminated via the study website, social media, in peer-reviewed scientific journals, at research conferences, local meetings and seminars and at a concluding dissemination and networking event for stakeholders.

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.

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.

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.

Prevalence and correlates of depressive symptoms among gay, bisexual and other men who have sex with men in the PROUD randomised clinical trial of HIV pre-exposure prophylaxis.

OBJECTIVES: The aim of this analysis is to: (i) assess the prevalence of clinically significant depressive symptoms at baseline and follow-up for participants in the PROUD trial of HIV pre-exposure prophylaxis (PrEP), examining changes in prevalence over time and (ii) investigate the association of socioeconomic and psychosocial factors with depression. METHODS: PROUD was an open label randomised trial evaluating the benefit of PrEP for 544 HIV-negative gay, bisexual and other men who have sex with men (GBMSM) in England. Enrolment was between 2012 and 2014, with at least 2 years follow-up. Prevalence of depression (score ≥10 on Patient Health Questionnaire-9) was assessed and compared across time-points (using McNemar's χ2 tests) and between trial arms (using χ2 tests). Cross-sectional associations with socioeconomic and psychosocial factors were examined using baseline data in modified Poisson regression models and combined 12 and 24 month follow-up data in generalised estimating equations (GEEs). Prevalence ratios (PRs) were presented as unadjusted PR and adjusted PR (aPR) for age, UK birth, sexual identity, university education, London study clinic site and calendar time (and follow-up time-point in GEEs). RESULTS: Depression increased significantly from baseline (9.1%; 49/540) to the 12 month (14.4%; 59/410) and 24 month (14.4%; 48/333) follow-ups, possibly explained by underreporting at baseline. The prevalence of depression did not differ by study trial arm, at any time-point. In the baseline analysis, younger age, unemployment and crystal methamphetamine use, was associated with depression. In combined analysis of 12 and 24 month data, measures of intimate partner violence (IPV) (lifetime IPV victimisation aPR 2.57 (95% CI: 1.71 to 3.86)), internalised homophobia (aPR 1.91 (95% CI: 1.29 to 2.83)) and concealment of sexual identity (aPR 1.75 (95% CI: 1.16 to 2.65)), were strongly associated with depression. CONCLUSIONS: There is a high concomitant burden of psychosocial factors with depression among GBMSM. TRIAL REGISTRATION NUMBER: ISRCTN (ISRCTN94465371) and ClinicalTrials.gov (NCT02065986).

Chemsex is not a barrier to self-reported daily PrEP adherence among PROUD study participants.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a novel HIV prevention method whereby HIV-negative individuals take the drugs tenofovir and emtricitabine to prevent HIV acquisition. Optimal adherence is critical for PrEP efficacy. Chemsex describes sexual activity under the influence of psychoactive drugs, in the UK typically; crystal methamphetamine, gamma-hydroxybutyrate(GHB) and/or mephedrone. Chemsex drug use has been associated with increased HIV transmission risk among gay, bisexual and other men who have sex with men (GBM) and poor ART adherence among people living with HIV. This study assessed whether self-reported chemsex events affected self-reported daily PrEP adherence among PROUD study participants. METHODS: The PROUD study was an open-label, randomised controlled trial, conducted in thirteen English sexual health clinics, assessing effectiveness of TruvadaⓇ-PrEP among 544 HIV-negative GBM. The study reported an 86% risk-reduction of HIV from daily PrEP. Participants were asked about chemsex engagement at follow-up visits. Monthly self-reports of missed PrEP tablets were aggregated to assess adherence between visits. Univariable and multivariable regression analyses were performed to test for associations between chemsex and reporting less than seven out of seven intended doses(<7/7ID) in the 7 days before and/or after last condomless anal intercourse(CAI). RESULTS: 1479 follow-up visit forms and 2260 monthly adherence forms from 388 participants were included in the analyses, with 38.5% visit forms reporting chemsex since last visit and 29.9% follow-up periods reporting <7/7ID. No statistically significant associations were observed between reporting <7/7ID and chemsex (aOR=1.29 [95% CI 0.90-1.87], p = 0.168). Statistically significant associations were seen between reporting <7/7ID and participants perceiving that they would miss PrEP doses during the trial, Asian ethnicity, and reporting unemployment at baseline. CONCLUSIONS: These analyses suggest PrEP remains a feasible and effective HIV prevention method for GBM engaging in chemsex, a practise which is prevalent in this group and has been associated with increased HIV transmission risk.

Outcome of an HIV education program for primary care providers: Screening and late diagnosis rates.

BACKGROUND: Late HIV diagnosis remains one of the challenges in combating the epidemic. Primary care providers play an important role in screening for HIV infection. Our study aims to evaluate the relationship between knowledge and barriers to HIV testing and screening outcomes. The impact of an education program for primary care providers, towards improving HIV testing and late diagnosis rates, is also assessed. METHODS: A self-administered questionnaire that was developed within the framework of the European project OptTEST was used to examine HIV knowledge and barriers to HIV testing scores before and after being involved in an HIV education program. A quasi-experimental design with pre- and post-intervention measures was performed to investigate its impact. We performed multivariable logistic regression analysis to assess the relationship between variables for the HIV testing offer. RESULTS: A total of 20 primary care centers and 454 primary care staff were included. Baseline OptTEST results showed that more knowledgeable staff offered an HIV test more frequently (OR 1.07; CI 95% 1.01-1.13; p = 0.027) and had lower barrier scores (OR 0.89; CI 95% 0.77-0.95; p = 0.005). Nurses had lower scores in knowledge-related items (OR 0.28; CI 95% 0.17-0.46; p<0.001), but higher scores in barrier-related items than physicians (OR 3.28; CI 95% 2.01-5.46; p<0.001). Specific centers with more knowledgeable staff members had a significant association with a greater level of new HIV diagnosis rates (OR 1.61; CI 95% 1.04-2.49; p = 0.032). After the intervention, we found that 12 out of 14 individual questions showed improved scores. In the 6 months after the training program, we similarly found a higher HIV testing rate (OR 1.19; CI 1.02-1.42; p = 0.036). CONCLUSIONS: This study highlights the association between knowledge and barriers to HIV testing, including HIV testing rates. It shows that it is possible to modify knowledge and reduce perceived barriers through educational programs, subsequently improving HIV screening outcomes.

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.

BASHH 2016 UK national audit and survey of HIV testing, risk assessment and follow-up: case note audit.

This national audit demonstrated discrepancies between actual practice and that indicated by clinic policies following enquiry about alcohol, recreational drugs and chemsex use. Clinics were more likely to enquire about risk behaviour if this was clinic policy or routine practice. Previous testing was the most common reason for refusing HIV testing, although 33% of men who have sex with men had a prior test of more than three months ago. Of the group declining due to recent exposure in the window period, 21/119 cases had an exposure within the four weeks prior to presentation, but had a previous risk not covered by previous testing. Recommendations include provision of risk assessments for alcohol, recreational drug use and chemsex, documenting reasons for HIV test refusal, provision of HIV point-of-care testing, follow-up for cases at higher risk of HIV and advice about community testing or self-sampling/testing.

Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort.

BACKGROUND: Deaths in HIV-positive people have decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996. Fewer AIDS-related deaths and an ageing cohort have resulted in an increase in the proportion of HIV patients dying from non-AIDS-related disorders. Here we describe mortality and causes of death in people diagnosed with HIV in the HAART era compared with the general population. METHODS: In this observational analysis, we linked cohort data collected by Public Health England (PHE) for individuals aged 15 years and older, diagnosed with HIV in England and Wales from 1997 to 2012, to the Office for National Statistics (ONS) national mortality register. Cohort inclusion began at diagnosis with follow-up clinical information collected every year from all 220 National Health Service (NHS) HIV outpatient clinics nationwide. To classify causes of death we used a modified Coding Causes of Death in HIV (CoDe) protocol, which uses death certificate data and clinical markers. We applied Kaplan-Meier analysis for survival curves and mortality rate estimation and Cox regression to establish independent predictors of all-cause mortality, adjusting for sex, infection route, age at diagnosis, region of birth, year of diagnosis, late diagnosis, and history of HAART. We used standardised mortality ratios (SMRs) to make comparisons with the general population. FINDINGS: Between 1997 and 2012, 88 994 people were diagnosed with HIV, contributing 448 839 person-years of follow up. By the end of 2012, 5302 (6%) patients had died (all-cause mortality 118 per 10 000 person-years, 95% CI 115-121). In multivariable analysis, late diagnosis was a strong predictor of death (hazard ratio [HR] 3·50, 95% CI 3·13-3·92). People diagnosed more recently had a lower risk of death (2003-07: HR 0·66, 95% CI 0·62-0·70; 2008-12: HR 0·65, 95% CI 0·60-0·71). Cause of death was determinable for 4808 (91%) of 5302 patients; most deaths (2791 [58%] of 4808) were attributable to AIDS-defining illnesses. Cohort mortality was significantly higher than the general population for all causes (SMR 5·7, 95% CI 5·5-5·8), particularly non-AIDS infections (10·8, 9·8-12·0) and liver disease (3·7, 3·3-4·2). All-cause mortality was highest in the year after diagnosis (SMR 24·3, 95% CI 23·4-25·2). INTERPRETATION: Despite the availability of free treatment and care in the UK, AIDS continues to account for the majority of deaths in HIV-positive people, and mortality remains higher in HIV-positive people than in the general population. These findings highlight the importance of prompt diagnosis, care engagement, and optimum management of comorbidities in reducing mortality in people with HIV. FUNDING: Public Health England.

HIV testing in Europe: Evaluating the impact, added value, relevance and usability of the European Centre for Disease Prevention and Control (ECDC)'s 2010 HIV testing guidance.

BACKGROUND: An evaluation of the 2010 ECDC guidance on HIV testing, conducted in October 2015-January 2016, assessed its impact, added value, relevance and usability and the need for updated guidance. METHODS: Data sources were two surveys: one for the primary target audience (health policymakers and decision makers, national programme managers and ECDC official contact points in the European Union/European Economic Area (EU/EEA) countries and one for a broader target audience (clinicians, civil society organisations and international public health agencies); two moderated focus group discussions (17 participants each); webpage access data; a literature citation review; and an expert consultation (18 participants) to discuss the evaluation findings. RESULTS: Twenty-three of 28 primary target audience and 31 of 51 broader target audience respondents indicated the guidance was the most relevant when compared with other international guidance. Primary target audience respondents in 11 of 23 countries reported that they had used the guidance in development, monitoring and/or evaluation of their national HIV testing policy, guidelines, programme and/or strategy, and 29 of 51 of the broader target audience respondents reported having used the guidance in their work. Both the primary and broader target audience considered it important or very important to have an EU/EEA-level HIV testing guidance (23/28 and 46/51, respectively). CONCLUSION: The guidance has been widely used to develop policies, guidelines, programmes and strategies in the EU/EEA and should be regularly updated due to continuous developments in the field in order to continue to serve as an important reference guidance in the region.

Enrichment of HLA Types and Single-Nucleotide Polymorphism Associated With Non-progression in a Strictly Defined Cohort of HIV-1 Controllers.

HIV-1 controllers (HIC) are extremely rare patients with the ability to control viral replication, maintain unchanging CD4 T-cell count, and evade disease progression for extensive periods of time, in the absence of antiretroviral therapy. In order to establish the representation of key genetic correlates of atypical disease progression within a cohort of HIV-1+ individuals who control viral replication, we examine four-digit resolution HLA type and single-nucleotide polymorphisms (SNP) previously identified to be correlated to non-progressive infection, in strictly defined HIC. Clinical histories were examined to identify patients exhibiting HIC status. Genomic DNA was extracted, and high definition HLA typing and genome-wide SNP analysis was performed. Data were compared with frequencies of SNP in European long-term non-progressors (LTNP) and primary infection cohorts. HLA-B alleles associated with atypical disease progression were at very high frequencies in the group of five HIC studied. All four HIC of European ancestry were HLA-B*57+ and half were also HLA-B*27+. All HIC, including one of self-reported African ethnicity, had the HLA-Cw*0602 allele, and the HLA-DQ9 allele was present only in HIC of European ancestry. A median 95% of the top 19 SNP known to be associated with LTNP status was observed in European HIC (range 78-100%); 17/19 of the SNP considered mapped to chromosome 6 in the HLA region, whereas 2/19 mapped to chromosome 8. The HIC investigated here demonstrated high enrichment of HLA types and SNP previously associated with long-term non-progression. These findings suggest that the extreme non-progressive phenotype considered here is associated with a genetic signature characterized by a single-genetic unit centered around the HLA-B*57 haplotype and the possible additive effect of HLA-B*27.

An effective strategy to diagnose HIV infection: findings from a national audit of HIV partner notification outcomes in sexual health and infectious disease clinics in the UK.

OBJECTIVES: Partner notification (PN) is a key public health intervention in the control of STIs. Data regarding its clinical effectiveness in the context of HIV are lacking. We sought to audit HIV PN outcomes across the UK. METHODS: All UK sexual health and HIV services were invited to participate. Clinical audit consisted of retrospective case-note review for up to 40 individuals diagnosed with HIV per site during 2011 (index cases) and a review of PN outcomes for up to five contacts elicited by PN per index case. RESULTS: 169/221 (76%) clinical services participated (93% sexual health/HIV services, 7% infectious diseases/HIV units). Most (97%) delivered PN for HIV. Data were received regarding 2964 index cases (67% male; 50% heterosexual, 52% white). PN was attempted for 88% of index cases, and outcomes for 3211 contacts were audited (from an estimated total of 6400): 519 (16%) were found not to be at risk of undiagnosed HIV infection, 1399 (44%) were informed of their risk and had an HIV test, 310 (10%) were informed of the risk but not known to have tested and 983 (30%) were not informed of their risk of HIV infection. Of 1399 contacts tested through PN, 293 (21%) were newly diagnosed with HIV infection. Regular partners were most likely to test positive (p<0.001). CONCLUSIONS: HIV PN is a highly effective diagnostic strategy. Non-completion of PN thus represents a missed opportunity to diagnose HIV in at-risk populations. Vigorous efforts should be made to pursue PN to identify people living with, and at risk of, HIV infection.

An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis.

BACKGROUND: Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. METHODS: The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). RESULTS: The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees. CONCLUSIONS: The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94465371 . Date of registration: 28 February 2013.

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.