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.

"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.

Infectious Proctitis due to Human Mpox.

We describe 2 cases of infectious proctitis secondary to human monkeypox in patients presenting with rectal pain. These cases highlight the importance of multidisciplinary management of monkeypox and in expanding case definitions and enabling clinical recognition in patients presenting without skin rash.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.

Complex PrEP: the factors requiring consultant-led review of PrEP users.

INTRODUCTION: HIV-1 pre-exposure prophylaxis (PrEP) has been available in England since March 2020 on the National Health Service using generic emtricitabine and tenofovir disoproxil. 56 Dean Street (56DS) provided PrEP through (1) additional private care from September 2015, estimated to be providing 11% of England's PrEP in 2019; and (2) the IMPACT trial, as well as monitoring those self-sourcing PrEP. Providing PrEP at scale through a nurse-led service required a safety net for complex individuals. 56DS introduced a consultant-led PrEP outpatient service, the PrEP review clinic, in January 2018 and we report the outcomes of this service. METHODS: We present a retrospective case note review of the PrEP review clinic with descriptive outcomes from 26 January 2018 to 20 December 2019. Reason for referral, demographics, PrEP management and PrEP discontinuations were recorded. RESULTS: 13 980 unique users accessed PrEP from 56DS during the two year evaluation period. 220 individuals were seen in the PrEP review clinic. Majority of patients were referred for renal issues (114 of 220, 51.8%), followed by side effects (59 of 220, 26.8%) and comorbidities (38 of 220, 17.2%). Of those with renal issues, 89 (out of 114, 78.1%) users were referred for an abnormal estimated glomerular filtration rate (eGFR). 35 (out of 114, 30.7%) PrEP users had an eGFR between 45 and 59 mL/min/1.73 m2, of whom 2 (5.7%) discontinued PrEP. Majority of users were advised to stop supplements±switch to event-based dosing (24 of 35, 68.6%). Ten PrEP users were referred with an eGFR between 30 and 44 mL/min/1.73 m2; 4 (40%) stopped or did not start PrEP and 6 (60%) were asked to stop supplements±switch to event-based dosing. DISCUSSION: A small proportion of PrEP users have complex PrEP issues. Methods to manage renal dysfunction with PrEP included stopping supplements and switching to event-based dosing. Those with side effects were managed with an array of options, with only modest effectiveness. Other PrEP options are needed to support those with toxicities or intolerances.

Treponema pallidum PCR testing for diagnosis of mucocutaneous ulcers suspicious for syphilis.

BACKGROUND: Primary syphilis is characterised by the appearance of an ulcerated lesion (chancre) on the anogenital or oral mucosa from which Treponema pallidum DNA may be detectable by PCR. Serological tests for syphilis may be non-reactive in early infection, even after the appearance of a chancre. We reviewed the use of a multiplex-PCR (M-PCR) test to determine the added value of T. pallidum DNA detection in the management of individuals presenting with mucocutaneous ulceration at a sexual health service in central London. METHODS: We performed a cross-sectional analysis of all individuals with detectable T. pallidum DNA from September 2019 to April 2020. Electronic patient records were reviewed and concomitant results for treponemal serology and/or rapid plasma reagin (RPR) extracted, along with demographic data, history of syphilis and indices of sexual behaviour including number of sexual partners contacted. Any subsequent treponemal serology and RPR results were also reviewed. RESULTS: M-PCR swab specimens were performed in 450 individuals, of whom 63 (14%) had detectable T. pallidum DNA; 60 of 63 (95%) were gay or bisexual men and 11 of 63 (17%) were living with HIV. A history of treated syphilis was present in 17 of 63 (27%). Same-day treponemal serology/RPR testing was performed in 58 of 63 (92%) patients. Of the 58 who had same-day syphilis serology/RPR, 9 (16%) had their syphilis infection confirmed by treponemal DNA PCR alone. A total of 165 partners were traced as contacts of infection, of whom 25 (15%) were contacts of individuals diagnosed by M-PCR testing alone. CONCLUSION: In individuals with T. pallidum PCR-positive lesions, around one in six in our cohort were negative on standard diagnostic serological tests for syphilis. Treponemal DNA testing is an important addition to serological assays in individuals with mucocutaneous ulceration who are at risk of recent syphilis infection and facilitates early diagnosis and contact tracing.

Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes.

INTRODUCTION: Preexposure prophylaxis (PrEP) is contributing to achieve a reduction in HIV diagnoses in men having sex with men (MSM). Albeit infrequent, HIV infections in the context of recent PrEP exposure represent a clinical challenge. METHODS: Data on recent PrEP use and possible reasons leading to HIV infection were analysed in individuals newly diagnosed with HIV at 56 Dean Street clinic in 2016-2020. Demographics, immune-virological parameters, genotypic resistance test results and treatment management in this group were compared with those not reporting recent PrEP exposure using Mann-Whitney U test and Fisher's exact test. RESULTS: Fifty-two of 1030 (5%) individuals reported recent PrEP exposure at HIV diagnosis; 98% were MSM, median age 34 years (interquartile range [IQR] 28-42), 65% of white ethnicity, 65% non-UK-born. 35% reported PrEP intake the day before testing HIV positive, 46% reported sub-optimal PrEP adherence since their last negative HIV test result. Thirty-three of 52 (63%) were self-sourcing PrEP and 9/52 (17%) reported issues with its supply. Recent PrEP use was associated to lower HIV viral load and higher CD4+ cell count at baseline than in counterparts non-recently exposed to PrEP (P < 0.01). M184V mutation was harboured more commonly in the recent PrEP use group (30% vs. 1%, P < 0.01). The proportion of individuals recently exposed to PrEP among those diagnosed with HIV rose sharply, reaching 21% in the first semester of 2020. Viral suppression was achieved by all patients intensified from PrEP to antiretroviral treatment (ART) who remained in care at week 24. DISCUSSION: Rapid PrEP intensification to ART allowed to achieve high rates of HIV viral suppression despite significant rates of M184V mutation harboured in those newly diagnosed with HIV and reporting recent PrEP exposure.

The success of HIV combination prevention: The Dean Street model.

The 56 Dean Street combination prevention model, a strong engagement with the LGBTQI community and flexible services adapted to users' changing needs led to an 80% drop in HIV diagnoses in gay, bisexual and other men who have sex with men (GBMSM) from 2015 to 2017. We describe the service changes at 56 Dean Street since 2012 which resulted in an increase in the frequency of HIV testing, the introduction of pre-exposure prophylaxis, earlier HIV diagnosis and a shorter time to viral suppression in those living with HIV. This model could be adapted to deliver similar results in those settings of high HIV prevalence among GBMSM and where access to technological innovation in healthcare and engagement with the community can be achieved.

Clinical and serological outcomes in patients treated with oral doxycycline for early neurosyphilis.

OBJECTIVES: Penicillin-based antibiotic treatment for syphilis infection with CNS involvement (early neurosyphilis) is not always a suitable treatment option. We compared outcomes of patients diagnosed with early neurosyphilis and treated with doxycycline or procaine G penicillin. METHODS: Serological and clinical outcomes were analysed in patients diagnosed with early neurosyphilis between January 2015 and October 2019 at 56 Dean Street, a combined sexual health and HIV service based in London, UK. Acute onset of CNS, ocular and/or otic symptomatology and a documented seroconverting syphilis serology or a >4-fold increase in rapid plasma reagin ('RPR)' test titre within the previous 12 months were criteria used to define a case. Mann-Whitney U-test and χ2 tests were used to test distributions between baseline characteristics and outcomes according to treatment administered. RESULTS: Eighty-seven patients were included: median age = 35 years (IQR = 31-45), 98% MSM, 79% white ethnicity, 53% HIV-1 positive and 40% previously diagnosed with syphilis at any stage. They were treated exclusively with either intramuscular (IM) procaine G penicillin (71%) or oral doxycycline (18%). Patients received doxycycline treatment over a penicillin-based regimen due to IM treatment declined (31%), inability to attend for IM injections (31%) or penicillin allergy (19%). Serological response was achieved by all patients; 91% reported full symptom resolution at 30 days from end of treatment. Similar rates of clinical and serological response and seroreversion were observed in the groups treated with procaine G penicillin versus doxycycline. CONCLUSIONS: The clinical and serological outcomes seen with penicillin-based versus doxycycline treatments were similar. A randomized controlled trial is needed to establish the effectiveness of doxycycline in the treatment of early neurosyphilis.

COVID-19 restrictions and changing sexual behaviours in HIV-negative MSM at high risk of HIV infection in London, UK.

OBJECTIVES: The COVID-19 pandemic and its related restrictions have affected attendance to and delivery of UK sexual healthcare services (SHS). We surveyed the impact on sexual behaviour of men having sex with men (MSM) to inform future SHS provision. METHODS: We conducted a cross-sectional, anonymous, web-based survey among HIV-negative MSM at high risk of HIV infection who attended 56 Dean Street, a sexual health and HIV clinic. The survey was conducted over a 7-day period in August 2020. Data on sociodemographic characteristics, sexual behaviour and related mental well-being experienced during lockdown (defined as 23 March-30 June 2020) were extracted. Categorical and non-categorical variables were compared according to HIV pre-exposure prophylaxis (PrEP) use. RESULTS: 814 MSM completed the questionnaire: 75% were PrEP users; 76% reported they have been sexually active, of which 76% reported sex outside their household. 75% reported fewer partners than prior to lockdown. Isolation/loneliness (48%) and anxiety/stress (27%) triggered sexual activity, and 73% had discussed COVID-19 transmission risks with their sexual partners. While 46% reported no change to emotions ordinarily experienced following sex, 20% reported guilt for breaching COVID-19 restrictions. 76% implemented one or more changes to their sexual behaviour, while 58% applied one or more steps to reduce COVID-19 transmission during sex. 36% accessed SHS and 30% reported difficulties in accessing testing/treatment. Of those who accessed SHS, 28% reported an STI diagnosis. PrEP users reported higher partner number, engagement in 'chemsex' and use of SHS than non-PrEP users. CONCLUSIONS: COVID-19 restrictions had a considerable impact on sexual behaviour and mental well-being in our survey respondents. High rates of sexual activity and STI diagnoses were reported during lockdown. Changes to SHS provision for MSM must respond to high rates of psychological and STI-related morbidity and the challenges faced by this population in accessing services.

Rapid ART start in early HIV infection: Time to viral load suppression and retention in care in a London cohort.

OBJECTIVES: Rapid antiretroviral therapy (ART) initiation is recommended in early HIV infection (EHI), even in the absence of baseline viral resistance test result. We analysed time to viral suppression according to ART regimen started in a cohort of patients diagnosed with EHI. METHODS: Clinical records of individuals consecutively diagnosed with EHI between July 2016-June 2018 were reviewed. The distribution of clinical, virological and immunological factors was compared in treatment groups using the Mann-Whitney U-test. RESULTS: 262 individuals (97% MSM) were diagnosed with EHI. 58% of patients agreed to start ART within 14 days of diagnosis. Tenofovir-based combinations were prescribed to all patients. DRV/b was the most commonly prescribed third agent (78%), when genotypic resistance testing was not available at time of ART choice. Switching to INSTI was encouraged once VRT became available and 27% switched from DRV/b to INSTI (mainly RAL) within 28 days from ART start. Those receiving INSTI were more likely to have a baseline viral load exceeding 1 million HIV-1 RNA copies/mL compared with those starting with DRV/b. Rapid start with INSTI regimens resulted in quicker viral suppression than when DRV/b was chosen in EHI, even when that was subsequently switched to INSTI. Retention in care following rapid ART start was achieved by all patients at 24 weeks. CONCLUSIONS: Starting an INSTI-based ART combination was associated with quicker viral suppression than when a protease inhibitor-based combination was chosen. No differences in the achievement of viral suppression or in retention in care were observed.

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.

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).

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.