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.

Barriers and facilitators to HIV Pre-Exposure Prophylaxis (PrEP) in Specialist Sexual Health Services in the United Kingdom: A systematic review using the PrEP Care Continuum.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) delivery in the UK is inequitable; over 95% of PrEP users were men who have sex with men (MSM) despite making up less than 50% of new HIV diagnoses. We conducted a systematic review to identify modifiable barriers and facilitators to PrEP delivery in the UK among underserved populations. METHODS: We searched bibliographic/conference databases using the terms HIV, PrEP, barriers, facilitators, underserved populations, and UK. Modifiable factors were mapped along the PrEP Care Continuum (PCC) to identify targets for interventions. RESULTS: In total, 44 studies were eligible: 29 quantitative, 12 qualitative and three mixed-methods studies. Over half (n = 24 [54.5%]) exclusively recruited MSM, whereas 11 were in mixed populations (all included MSM as a sub-population) and the other nine were in other underserved populations (gender and ethnicity minorities, women, and people who inject drugs). Of the 15 modifiable factors identified, two-thirds were at the PrEP contemplation and PrEParation steps of the PCC. The most reported barriers were lack of PrEP awareness (n = 16), knowledge (n = 19), willingness (n = 16), and access to a PrEP provider (n = 16), whereas the more reported facilitators were prior HIV testing (n = 8), agency and self-care (n = 8). All but three identified factors were at the patient rather than provider or structural level. CONCLUSIONS: This review highlights that the bulk of the scientific literature focuses on MSM and on patient-level factors. Future research needs to ensure underserved populations are included and prioritized (e.g. ethnicity and gender minorities, people who inject drugs) and provider and structural factors are investigated.

Impact of daily, oral pre-exposure prophylaxis on the risk of bacterial sexually transmitted infections among cisgender women: a systematic review and narrative synthesis.

Background: There are concerns that the use of pre-exposure prophylaxis (PrEP) may result in an increased incidence of sexually transmitted infections (STIs). Evidence for this is mixed and has mostly been based on reviews focussed on gay and bisexual men and transgender women, while none have summarised evidence in cisgender women. Methods: We conducted a systematic review to explore whether daily, oral PrEP use is associated with changes in bacterial STI occurrence (diagnoses or self-reported) and/or risk among HIV seronegative cisgender women (ciswomen). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. Results: We included 11 full text articles in a narrative synthesis, with the studies published between 2012 and 2021. The studies were mostly based in Africa (n=7, 63.6%) and reported on 3168 ciswomen using PrEP aged 16-56 years. Studies had marked differences in variables, including measurements and definitions (e.g., STI type) and limited data available looking specifically at ciswomen, principally in studies with both male and female participants. The limited evidence suggests that PrEP use is not associated with increased STI rates in ciswomen generally; however, adolescent girls and young women in Sub Saharan Africa have a higher prevalence of bacterial STIs prior to PrEP initiation, compared to adult ciswomen and female sex workers. Conclusions: We suggest future PrEP research make efforts to include ciswomen as study participants and report stratified results by gender identity to provide adequate data to inform guidelines for PrEP implementation. PROSPERO registration: CRD42019130438.

Assessment of mortality and hospital admissions associated with confirmed infection with SARS-CoV-2 Alpha variant: a matched cohort and time-to-event analysis, England, October to December 2020.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

Aberrant subcutaneous adipogenesis precedes adult metabolic dysfunction in an ovine model of polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS) affects over 10% of women. Insulin resistance, elevated free fatty acids (FFAs) and increased adiposity are key factors contributing to metabolic dysfunction in PCOS. We hypothesised that aberrant adipogenesis during adolescence, and downstream metabolic perturbations, contributes to the metabolic phenotype of adult PCOS. We used prenatally androgenised (PA) sheep as a clinically realistic model of PCOS. During adolescence, but not during fetal or early life of PA sheep, adipogenesis was decreased in subcutaneous adipose tissue (SAT) accompanied by decreased leptin, adiponectin, and increased FFAs. In adulthood, PA sheep developed adipocyte hypertrophy in SAT paralleled by increased expression of inflammatory markers, elevated FFAs and increased expression of genes linked to fat accumulation in visceral adipose tissue. This study provides better understanding into the pathophysiology of PCOS from puberty to adulthood and identifies opportunity for early clinical intervention to normalise adipogenesis and ameliorate the metabolic phenotype.

HPV vaccination of gay, bisexual and other men who have sex with men in sexual health and HIV clinics in England: vaccination uptake and attendances during the pilot phase.

BACKGROUND: Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase. METHODS: Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination. RESULTS: Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC. CONCLUSIONS: HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.