Alan McOwan

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.

There is such a thing as asking for trouble: taking rapid HIV testing to gay venues is fraught with challenges.

Objectives: To explore the feasibility and acceptability of offering rapid HIV testing to men who have sex with men in gay social venues. Methods: Qualitative study with in-depth interviews and focus group discussions. Interview transcripts were analysed for recurrent themes. 24 respondents participated in the study. Six gay venue owners, four gay service users and one service provider took part in in-depth interviews. Focus groups were conducted with eight members of a rapid HIV testing clinic staff and five positive gay men. Results: Respondents had strong concerns about confidentiality and privacy, and many felt that HIV testing was “too serious” an event to be undertaken in social venues. Many also voiced concerns about issues relating to post-test support and behaviour, and clinical standards. Venue owners also discussed the potential negative impact of HIV testing on social venues. Conclusion: There are currently substantial barriers to offering rapid HIV tests to men who have sex with men in social venues. Further work to enhance acceptability must consider ways of increasing the confidentiality and professionalism of testing services, designing appropriate pre-discussion and post-discussion protocols, evaluating different models of service delivery, and considering their cost-effectiveness in relation to existing services.

Identifying undiagnosed HIV in men who have sex with men (MSM) by offering HIV home sampling via online gay social media: a service evaluation

Background An estimated one in eight men who have sex with men (MSM) in London lives with HIV, of which 16% are undiagnosed. It is a public health priority to minimise time spent undiagnosed and reduce morbidity, mortality and onward HIV transmission. ‘Dean Street at Home’ provided an online HIV risk self-assessment and postal home HIV sampling service aimed at hard-to-reach, high-risk MSM. Objectives This 2-year service evaluation aims to determine the HIV risk behaviour of users, the uptake of offer of home sampling and the acceptability of the service. Methods Users were invited to assess their HIV risk anonymously through messages or promotional banners on several gay social networking websites. Regardless of risk, they were offered a free postal HIV oral fluid or blood self-sampling kit. Reactive results were confirmed in clinic. A user survey was sent to first year respondents. Results 17 361 respondents completed the risk self-assessment. Of these, half had an ‘identifiable risk’ for HIV and a third was previously untested. 5696 test kits were returned. 121 individuals had a reactive sample; 82 (1.4% of returned samples) confirmed as new HIV diagnoses linked to care; 14 (0.25%) already knew their diagnosis; and 14 (0.25%) were false reactives. The median age at diagnosis was 38; median CD4 505 cells/µL and 20% were recent infections. 61/82 (78%) were confirmed on treatment at the time of writing. The post-test email survey revealed a high service acceptability rate. Conclusions The service was the first of its kind in the UK. This evaluation provides evidence to inform the potential roll-out of further online strategies to enhance community HIV testing.

Diagnostics within the clinic to test for gonorrhoea and chlamydia reduces the time to treatment: a service evaluation

Rapid on-site diagnostics permit prompt recognition and treatment of infections. We introduced the GeneXpert system (Cepheid, California, USA) within 56 Dean Street, a central London sexual health clinic. The machine processes Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) samples in 90 min by real-time PCR. We present the results of the service evaluation of a pilot where GeneXpert was used to process samples from individuals attending outreach or specialised clinics. Asymptomatic attenders whose samples were processed using the GeneXpert system were compared with asymptomatic ‘standard of care’ …

Rapidly declining HIV infection in MSM in central London

In 2016, there were 1·8 million new HIV infections worldwide. Although the annual number of new HIV infections has fallen by 16% since 2010, the rate of decline is far too slow to meet the fast-track target of 500 000 new infections per year, agreed at the UN General Assembly in 2016. We still have no cure or effective vaccine to prevent HIV. There are, however, many HIV prevention approaches available, including rapid treatment of those diagnosed with HIV to render them uninfectious— the treatment as prevention strategy. This has been an important UNAIDS policy to diminish the global burden of HIV by achieving the 90-90-90 metric by 2020 and embraced by the fast-track cities campaign. In some countries where 90-90-90 has been or has almost been achieved, incidence rates have not declined meaningfully, but in others such as Swaziland, where there is a comprehensive test-and-treat programme linked to prevention including voluntary medical male circumcision, incidence has fallen by 44%. Until 2015, new HIV infections in the UK were relatively stable, with a total of 6286 infections in that year. In 2016, Public Health England reported an 18% reduction in new diagnoses, with a 21% decrease among gay and bisexual men, a group in whom diagnoses had steadily been increasing since 2007. The reduced incidence in gay and bisexual men was most pronounced in London, in whom there was a 29% decrease with an overall decline in infections in gay men outside London of 11%. The accepted explanation for this significant change was a large increase in HIV tests among gay and bisexual men attending sexual health clinics (from 37 224 in 2007 to 143 560 in 2016), including repeat testing in higher risk men and improvements in the uptake of ART after HIV diagnosis. However, increased screening probably provides only a partial explanation. 56 Dean Street, a sexual health service in London, diagnoses one in three new HIV infections in the capital and sees a quarter of newly diagnosed individuals in the UK. Since 2015, the clinic has seen an 80% reduction in diagnoses (figure). Similar trends have been seen in four other large London clinics. The decline in new infections seen at Dean Street occurred against a background of a significant increase in testing in high-risk gay men in 2014–15 which subsequently stabilised. Other important factors might have also played a part. Patients at the clinic commence HIV treatment within a median of 7 days of diagnosis. Whether this contributes substantially to a decrease in transmission deserves further study because knowledge of HIV status alone is associated with a reduction in risk behaviour for a variable period of time after diagnosis. Another important factor that needs to be considered as a major contributor to the decline in diagnoses is the use of HIV pre-exposure prophylaxis (PrEP). In the Autumn of 2014, the PROUD and IPERGAY PrEP studies were stopped early, after both showed an 86% reduction in HIV acquisition risk for people taking tenofovir disoproxil fumarate plus emtricitabine versus placebo. Gay men began to purchase generic PrEP from India as it is not available through the UK health system. This was facilitated by community activists who set up I Want PrEP Now offering advice and links to online pharmacies for people seeking to purchase PrEP on the internet. At the same time, 56 Dean Street launched a service offering support and monitoring for people buying generics online, including drug concentration testing to ensure authenticity. In addition, Dean Street PRIME, an intervention for people with at least a 10% chance For more on I Want PrEP Now see www.iwantprepnow.co.uk Published Online October 20, 2017 http://dx.doi.org/10.1016/ S2352-3018(17)30181-9

Not just PrEP: other reasons for London's HIV decline

www.thelancet.com/hiv Vol 4 April 2017 e153 Diagnoses started to fall in the autumn of 2015 (figure). In 2014, we opened Dean Street Express, reducing time to treatment for chlamydia and gonorrhoea from 10 days to 2 days. Given that both these infections are drivers of HIV transmission, their early treatment may have played a part in the decline in new infections. Additionally, the opening of Dean Street Express was linked to a significant increase in HIV testing in high risk men who have sex with men (MSM). Other factors likely to have had an effect are that we prescribe over a quarter of the HIV post-exposure prophylaxis in the UK (2637 of 9609 prescriptions in 2015), and the Dean Street Wellbeing Programme promoting regular testing in high risk MSM, including those practising chemsex. Not just PrEP: other reasons for London’s HIV decline

High HIV incidence in men who have sex with men following an early syphilis diagnosis: is there room for pre-exposure prophylaxis as a prevention strategy?

Objectives HIV pre-exposure prophylaxis (PrEP) is becoming a pivotal strategy for HIV prevention. Understanding the impact of risk factors for HIV transmission to identify those at highest risk would favour the implementation of PrEP, currently limited by costs. In this service evaluation, we estimated the incidence of bacterial STIs in men who have sex with men (MSM) diagnosed with early syphilis attending a London sexual health clinic according to their HIV status. In addition, we estimated the incidence of HIV infection in HIV-negative MSM, following a diagnosis of early syphilis. Methods We undertook a retrospective case note review of all MSM patients diagnosed with early syphilis between January and June 2014. A number of sexual health screens and diagnoses of chlamydia, gonorrhoea and HIV were prospectively analysed following the syphilis diagnosis. Results 206 MSM were diagnosed with early syphilis. 110 (53%) were HIV-negative at baseline, 96 (47%) were HIV-positive. Only age (37 vs 32 years, p=0.0005) was significantly different according to HIV status of MSM at baseline. In HIV-negative versus HIV-positive MSM, incidence of rectal chlamydia infection at follow-up was 27 cases vs 50/100 person-years of follow-up (PYFU) (p=0.0039), 33 vs 66/100 PYFU (p=0.0044) for rectal gonorrhoea and 10 vs 26/100 PYFU (p=0.0044) for syphilis reinfection, respectively. Total follow-up for 110 HIV-negative MSM was 144 person-years. HIV incidence was 8.3/100 PYFU (CI 4.2 to 14). Conclusions A diagnosis of early syphilis carries a high risk of consequent HIV seroconversion and should warrant prioritised access to prevention measures such as PrEP and regular STI screening to prevent HIV transmission.

Outcomes of acutely HIV-1-infected individuals following rapid antiretroviral therapy initiation.

BACKGROUND Few data exist on the benefits and acceptability of rapid initiation of antiretroviral treatment in acute HIV infection (AHI). We analysed a large cohort of acutely infected HIV patients starting antiretroviral therapy (ART) to determine uptake, linkage into care and time to achieve viral suppression. METHODS Case notes of all individuals diagnosed with AHI between May 2014 and October 2015 at 56 Dean Street, a sexual health clinic in London, UK were reviewed. AHI was defined through documentation of plasma HIV RNA positivity only, plasma HIV RNA and p24 antigen positivity with a negative HIV enzyme immunoassay (EIA) test or HIV EIA test switching from negative to positive within 6 weeks. Between-group comparisons of time to viral suppression according to ART chosen were performed using the log-rank test. RESULTS We identified 113 individuals with AHI. Linkage to care was 95%. 77% of patients started ART at first medical appointment: all men who have sex with men, median age 35 years, median viral load (VL) log10 6.45, median CD4+ T-cell count 483 cells/mm3. Median time from diagnosis to ART initiation was 20 days. At 24 weeks, no patients had discontinued ART; 99% of patients achieved viral suppression by 24 weeks, with a median time to documented VL suppression of 74 days. Viral suppression was more rapid with integrase inhibitors compared with other regimens (median 41 versus 88.5 days, P<0.05). CONCLUSIONS In acute HIV infection, individuals demonstrated high ART uptake and rapid VL suppression suggesting that early treatment with antiretrovirals is acceptable and efficacious.

O19 Can express treatment reduce onward transmission

Background/introduction The introduction of onsite Cepheid® GeneXpert diagnostics for asymptomatic STI screens cut ‘test to treatment’ time by 190 h. Aim(s)/objectives To evaluate the Public Health benefit of faster treatment. Methods Patients with chlamydia (CT) and/or gonorrhoea (GC) over 8 weeks in February 2014 were retrospectively identified. We compared the timing of testing, treatment and number of recent sexual partners with a control group from November 2013. Assuming rate of partners remains unchanged, we calculated ‘partners spared’ exposure per infected patient due to faster treatment. Results 431 patients were identified with CT and/or GC infection. 81% (349/431) were MSM. Median age was 29 years. 23% of index patients disclosed high risk behaviour including fisting, chemsex and injecting drug use. Median ‘test to treatment’ time dropped from 238 h to 48 h. The number of partners spared exposure was 0.5 per index case. This equates to a total 196 partners spared exposure over the study period. Discussion/conclusion For every two people diagnosed with an infection, one partner was spared exposure. Limiting the duration of infectivity and the potential for onward transmission has clear public health benefits and is of particular value in this cohort with multiple partners who engage in high-risk behaviour.

Interventions to increase access to STI services: a study of England's ‘high-impact changes’ across three central London clinics

Background Increasing access to sexual health services is a key objective for the Department of Health in England and Wales. In 2006 it published 10 high-impact changes (HICs) designed to enhance 48 h access to genitourinary medicine services. However, there is limited evidence on the effectiveness of the proposed interventions. Objective To evaluate the implementation of five HICs in three sexual health clinics over 4 years. These HICs included a text message results service, nurse-delivered asymptomatic service, clinic refurbishment, a centralised booking service and an electronic appointment system. Methods The effect of HICs was evaluated by measuring clinical activity, number of sexual health screens performed, and patients seen within 48 h. These data were obtained from the clinic database, mandatory reports and Health Protection Agency waiting time surveys, respectively. Results The median number of new patients seen per month increased from 3635 to 4263 following the implementation of the five HICs. The follow-up/new patient ratio fell from 0.67 to 0.21 during the study. The biggest fall corresponded to a rise in patients receiving results by text message, from 0% to 40%. Only the centralised booking service was associated with a significant increase in the number of new patients seen. Discussion Providing results by text message was associated with a reduced number of follow-up patients, while implementation of a centralised booking service coincided with a significant increase in patient access. Further research is required to evaluate the relative importance of the other HICs.