Monica Desai

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

Summary 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.

Healthcare providers' knowledge of, attitudes to and practice of pre-exposure prophylaxis for HIV infection.

Pre‐exposure prophylaxis (PrEP) has proven biological efficacy in reducing the risk of sexual acquisition of HIV. Healthcare providers (HCPs) knowledge of and attitudes to PrEP will be key to successful implementation. In England, PrEP is only available to men who have sex with men (MSM) through the open‐label randomized PROUD pilot study of immediate or deferred use.

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

BackgroundPre-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 86xa0% 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.MethodsThe 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 12xa0months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90xa0days. 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).ResultsThe median age of participants was 35 (IQR: 29–43). Typically participants were white (81xa0%), educated at a university level (61xa0%) and in full-time employment (72xa0%). Of all participants, 217 (40xa0%) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12xa0months in 330/515 (64xa0%) and 473/544 (87xa0%) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17xa0%) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5–20) partners in the last 90xa0days, 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 (34xa0%) participants in the past 12xa0months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees.ConclusionsThe 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 registrationCurrent Controlled TrialsISRCTN94465371. Date of registration: 28 February 2013.

Ongoing outbreak of invasive and non-invasive disease due to group A Streptococcus (GAS) type emm66 among homeless and people who inject drugs in England and Wales, January to December 2016

We report an outbreak of invasive and non-invasive disease due to an unusual type of Streptococcus pyogenes(group A Streptococcus, emm66) among a vulnerable, largely homeless population in southern England and Wales, detected in September 2016. Twenty-seven confirmed cases were subsequently identified between 5 January and 29 December 2016; 20 injected drugs and six reported problematic alcohol use. To date, we have ruled out drug-related vehicles of infection and identified few common risk factors.

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation

BACKGROUNDnIn the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain.nnnMETHODSnIn this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs.nnnFINDINGSnIntroduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40u2008000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40u2008000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex.nnnINTERPRETATIONnThis analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised.nnnFUNDINGnNational Institute for Health Research.

‘Slamming’ among men who have sex with men accessing general drug services, in response to Schmidt, AJ et al., 2016, Illicit drug use among gay and bisexual men in 44 cities: Findings from the European MSM Internet Survey (EMIS)

Schmidt et al. (2016) findings suggested high levels of sexualised drug use among men who have sex with men (MSM) in a number of UK cities, namely Brighton, Manchester and London. The extent of the use of various drugs, including those associated with sexualised drug use, among MSM found in the study is likely to be overestimated due to the potentially leading nature of questions asked about drugs (“When was the last time you consumed . . . ”) which could be perceived to be presenting drug use as normal. Additionally, the online sample approach may have over-sampled higher risk groups using the internet, as identified in the study’s limitations, for example those using it to meet others for sex (Schmidt et al., 2016; Platt et al., 2015). However, of concern, the recent UK’s ‘Shooting up’ report highlighted a high prevalence of the injection of drugs associated with sexualised drug use, particularly among MSM who had recently started injecting and attending general drug services (Public Health England et al., 2016). This sexualised injecting drug use, or ‘Slamming’, has previously been reported among some groups of HIV positive MSM primarily attending sexual health and specialist LGBT drug services (Mohammed et al., 2016; Kirby & Thornber-Dunwell, 2013; Erica et al., 2016). The Unlinked and Anonymous Monitoring (UAM) survey of people who inject drugs (PWID) is a surveillance system conducted in general drug services (including needle and syringe programmes) across England, Wales and Northern Ireland. Since 2000, the proportion of male PWID recruited who reported sex with men has increased (4.4% in 2000/01 to 8.4% in 2014/15, p < 0.001), as has prevalence of HIV among this group (2.2%–8.3%, p = 0.22). Drug use patterns have altered, with increasing stimulant injection (57%–77%, p < 0.001) and decreasing opiate injection (80%–65%, p < 0.001) among MSM.

Recent advances in pre-exposure prophylaxis for HIV

Abstract Although pre-exposure prophylaxis (PrEP)—the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV—is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation.

Cost and cost-effectiveness of an HIV pre-exposure prophylaxis (PrEP) programme for high-risk men who have sex with men in England: results of a static decision analytical model

Abstract Background The efficacy and effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV infection acquisition by high-risk men who have sex with men (MSM) is established. We estimated the cost and cost-effectiveness of a proposed daily oral PrEP programme covering 10u2008000 high-risk MSM attending genitourinary medicine clinics in England. Methods From the perspective of public providers, a static decision analytical model was used to investigate lifetime HIV infections, treatment costs, and quality-adjusted-life-year (QALY) losses associated with daily PrEP given for 1 year, beginning in 2016, compared with no intervention. A cohort of MSM who were not known to be HIV positive at their first attendance in 2012 and had tested HIV negative between 42 and 365 days previously was identified. These men were followed up from the date of their earliest negative HIV test in 2012 for up to 1 year either until they seroconverted or until their last attendance. HIV incidence was calculated as the number of seroconversions (new HIV diagnoses) per 100 person-years. Data sources including genitourinary medicine clinic activity data were used to estimate HIV incidence in year 1 and thereafter. Costs were updated to 2013–14 values and both future costs and QALYs were discounted at 3·5%. Budgetary impact was undiscounted. Findings At 86% effectiveness, delivery of PrEP to 10u2008000 high-risk MSM in the first year (target population with an HIV incidence of 2·4 per 100 person-years in year 1) resulted in 178 fewer lifetime HIV infections, 28 delayed infections, and an incremental cost-effectiveness ratio (ICER) of £26u2008300, compared with no PrEP. More conservative assumptions of 64% PrEP effectiveness gave an ICER of £54u2008500, compared with no PrEP. ICER was highly sensitive to year 1 HIV incidence (eg, with HIV incidence of 3·3 per 100 person-years and at 86% PrEP effectiveness, ICER was £4170), PrEP effectiveness, PrEP drug costs, and potential changes in antiretroviral treatment cost upon patent expiry. An investment of £54 million in year 1 breaks even anywhere from year 42 (86% PrEP effectiveness) to beyond year 61 (64% PrEP effectiveness). Interpretation The model shows that the estimated cost-effectiveness of PrEP is very sensitive to key variables (eg, year 1 HIV incidence and patient adherence), about which there is much uncertainty, especially if programme scale-up occurs. A substantial reduction in the price of antiretroviral drugs, when used for PrEP, is needed to give the necessary assurance of cost-effectiveness, and for an affordable public health programme of sufficient size. Funding None.

Information for action: a method to inform HIV shared care planning in primary care at the PCT level

Increasing HIV patient numbers, emerging comorbidities and an ageing patient population support the need for HIV shared care service delivery models in the UK.1–3 The British HIV Association recommends that HIV patients register with a general practitioner (GP) and disclose their status, but the limited data available suggest disclosure is variable.4 5 Successful shared care planning depends on understanding the local HIV-infected population and the proportion of HIV infections disclosed …

Sexualised drug use in the United Kingdom (UK): A review of the literature

BACKGROUNDnSexualised drug use (SDU) refers to the use of drugs in a sexual context. This includes Chemsex- the use of drugs (specifically crystal methamphetamine, GHB/GBL and mephedrone) before or during planned sexual activity to sustain, enhance, disinhibit or facilitate the experience. Here we aimed to synthesise available UK prevalence data for Chemsex, SDU and the use of Chemsex drugs in an undefined context (CDU) in men who have sex with men (MSM).nnnMETHODSnPapers published between January 2007 and August 2017 reporting Chemsex, SDU and/or Chemsex drug use (CDU) prevalence in MSM were identified through PubMed. Citations were searched for further eligible publications. We also conducted a review of national surveillance data, extracting prevalence data for Chemsex, SDU or CDU. Synthesized data were then assessed to determine the time at which these drugs were taken, in this case just prior to or during sexual activity (event-level).nnnRESULTSnOur search identified 136 publications, of which 28 were included in the final data synthesis. Three of the four surveillance systems assessed provided SDU or CDU data in MSM. Few publications included event-level data for Chemsex (nu202f=u202f4), with prevalence estimates ranging from 17% among MSM attending sexual health clinics (SHC) to 31% in HIV-positive MSM inpatients. Prevalence estimates for SDU (nu202f=u202f7 publications) also varied considerably between 4% in MSM receiving HIV care to 41% among MSM attending SHC for HIV post-exposure prophylaxis (PEP). Eighteen publications provided data for CDU.nnnCONCLUSIONnPrevalence estimates varied considerably due to differences in the definition used and population assessed. Standardised definitions and studies with representative national samples of MSM are required to improve our understanding of the extent of Chemsex and its associated risks. Longitudinal event-level data for SDU and Chemsex are needed to monitor impact of interventions.