Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.

Overcoming barriers to HIV pre-exposure prophylaxis (PrEP) coverage in Australia among Medicare-ineligible people at risk of HIV: results from the MI-EPIC clinical trial.

Background Overseas-born people who are ineligible for government-subsidised health care experience barriers to accessing HIV pre-exposure prophylaxis (PrEP) in Australia. This study aimed to assess a program providing free PrEP to overseas-born adults at risk of acquiring HIV. Methods Medicare-Ineligible Expanded Implementation in Communities (MI-EPIC) was a single-arm, open-label trial of daily tenofovir disoproxil fumarate/emtricitabine as PrEP. Six clinics recruited Medicare-ineligible adults who met HIV risk criteria in New South Wales, Australia. We recorded data on HIV and sexually transmitted infection (STI) diagnoses, and PrEP dispensing from July 2019 to June 2020. PrEP adherence as a medication possession ratio (MPR) was calculated as pills dispensed divided by days. We administered an optional survey on behaviours and attitudes to PrEP and sexual health. Results The 221 participants (206 men; 93.2%) had a median age of 29years (IQR 26-34). Participants were mostly born in Asia (53.4%), Latin America or the Caribbean (25.3%), or Europe (10.9%). Adherence was high; 190 participants (86.0%) had an MPR of >60%. Of 121 survey participants, 42 (34.7%) completed the survey in a language other than English. Of participants who had not used PrEP in the 6months before enrolment (n=45, 37.2%), the most common reasons were cost (n=22, 48.9%), and lack of knowledge about accessing PrEP (n=20, 44.4%). Conclusions Medicare-ineligible people at risk of HIV demonstrate high adherence when given access to free PrEP and translated information. Increasing PrEP awareness and reducing barriers to accessing PrEP in this high-risk population should be priorities in HIV prevention.

Progress Towards Elimination of Hepatitis C Infection Among People Who Inject Drugs in Australia: The ETHOS Engage Study.

BACKGROUND: Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. METHODS: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). RESULTS: Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00-2.16), incarcerated in the previous year (2.04; 1.38-3.02), and those injecting drugs daily or more (2.26; 1.43-2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48-.95), participants who were homeless (.59; .38-.96), and those injecting daily or more (.51; .31-.89). People aged ≥45 years (1.46; 1.06-2.01) and people receiving OAT (2.62; 1.52-4.51) were more likely to report HCV treatment. CONCLUSIONS: Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment.

Expanded HIV pre-exposure prophylaxis (PrEP) implementation in communities in New South Wales, Australia (EPIC-NSW): design of an open label, single arm implementation trial.

BACKGROUND: The New South Wales (NSW) HIV Strategy 2016-2020 aims for the virtual elimination of HIV transmission in NSW, Australia, by 2020. Despite high and increasing levels of HIV testing and treatment since 2012, the annual number of HIV diagnoses in NSW has remained generally unchanged. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV infection among gay and bisexual men (GBM) when taken appropriately. However, there have been no population-level studies that evaluate the impact of rapid PrEP scale-up in high-risk GBM. Expanded PrEP Implementation in Communities in NSW (EPIC-NSW) is a population-level evaluation of the rapid, targeted roll-out of PrEP to high-risk individuals. METHODS: EPIC-NSW, is an open-label, single-arm, multi-centre prospective observational study of PrEP implementation and impact. Over 20 public and private clinics across urban and regional areas in NSW have participated in the rapid roll-out of PrEP, supported by strong community mobilization and PrEP promotion. The study began on 1 March 2016, aiming to enroll at least 3700 HIV negative people at high risk of HIV. This estimate took into consideration criteria for PrEP prescription in people at high risk for acquiring HIV as defined in the NSW PrEP guidelines. Study participants receive once daily co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and are followed for up to 24 months. Follow-up includes: testing for HIV at 1 month, HIV and other sexually transmissible infections three-monthly, HCV annually and monitoring of renal function six-monthly. Optional online behavioural surveys are conducted quarterly. The co-primary endpoints are (i) HIV diagnoses and incidence in the cohort and (ii) HIV diagnoses in NSW. DISCUSSION: EPIC-NSW is a population-based PrEP implementation trial which targets the entire estimated population of GBM at high risk for HIV infection in NSW. It will provide a unique opportunity to evaluate the population impact of PrEP on a concentrated HIV epidemic. TRIAL REGISTRATION: https://clinicaltrials.gov/ (identifying number NCT02870790 ; registration date 14 August 2016), pre-results stage.

Correction: expanded HIV pre-exposure prophylaxis (PrEP) implementation in communities in new South Wales, Australia (EPIC-NSW): design of an open label, single arm implementation trial.

After publication of the article [1], it has been brought to our attention that one of the members of the EPIC-NSW study group has had their name spelt incorrectly in the acknowledgements. The article mentions "Muhammad Hammoud" when in fact the correct spelling is "Mohamed Hammoud".

Adherence to daily HIV pre-exposure prophylaxis in a large-scale implementation study in New South Wales, Australia.

OBJECTIVES: To examine patterns of long-term pre-exposure prophylaxis (PrEP) adherence and its association with HIV seroconversion in NSW, Australia. DESIGN: Population-based HIV PrEP implementation study. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an open-label study of daily oral PrEP which recruited participants from March 2016 to April 2018. Adherence was measured using dispensing records. PrEP discontinuation was defined as an at least 120-day period without PrEP coverage. Long-term adherence patterns were identified using group-based trajectory modelling. RESULTS: Participants dispensed at least once (n = 9586) were almost all male (98.5%), identified as gay (91.3%), with a median age of 34 years (range: 18-86). Of the 6460 (67.4%) participants who had at least 9 months of follow-up since first dispensing, 1942 (30.1%) discontinued. Among these, 292 (15.0%) restarted later. Four distinct groups were identified ['Steep decline' in adherence (15.8%), 'Steady decline' (11.6%), 'Good adherence' (37.4%), and 'Excellent adherence' (35.2%)]. Older (P < 0.001) and gay-identified (P < 0.001) participants were more likely to have higher adherence, so were those living in postcodes with a higher proportion of gay-identified male residents (P < 0.001). Conversely, those who at baseline reported recent crystal methamphetamine use and had a recent diagnosis of sexually transmitted infection (STI) had lower adherence (P < 0.001). Overall HIV incidence was 0.94 per 1000 person-years (95% confidence interval: 0.49-1.81; n = 9) and was highest in the 'steep decline' group (5.45 per 1000 person-years; P = 0.001). CONCLUSION: : About 15% of participants stopped PrEP during study follow-up and were at increased risk of HIV infection. They were more likely to be younger and report a recent STI or methamphetamine use prior to PrEP initiation.

The 2016 HIV diagnosis and care cascade in New South Wales, Australia: meeting the UNAIDS 90-90-90 targets.

INTRODUCTION: The HIV Strategy in New South Wales (NSW) Australia aims to virtually eliminate HIV transmission by 2020. We estimated the 2016 HIV diagnosis and care cascade for the state of NSW, with a focus on introducing population-based data to improve data quality and assess progress towards the UNAIDS 90-90-90 targets. METHODS: To estimate the number of people living with diagnosed HIV (PLDHIV) we used NSW data from the Australian National HIV Registry, enhanced by surveillance among people recently diagnosed with HIV to improve migration estimates. The number of undiagnosed PLHIV was estimated using back-projection modelling by CD4 count at diagnosis. De-duplicated prescription claims data were obtained from the Australian Pharmaceutical Benefits Scheme (PBS), and were combined with an estimate for those ineligible, to determine the number of PLDHIV on antiretroviral therapy (ART). Data from a clinic network with 87% coverage of PLDHIV in NSW enabled the estimation of the number on ART who had HIV suppression. RESULTS AND DISCUSSION: We estimated that 10,110 PLHIV resided in NSW in 2016 (range 8400 to 11,720), among whom 9230 (91.3%) were diagnosed, and 8490 (92.0% of those diagnosed) were receiving ART. Among PLDHIV receiving ART, 8020 (94.5%) had suppressed viral load (<200 HIV-1 RNA copies/mL). Overall, 79.3% of all PLHIV had HIV virological suppression. CONCLUSION: NSW has met each of the UNAIDS 90-90-90 targets. The enhanced surveillance methods and data collection systems improved data quality. Measuring and meeting the 90-90-90 targets is feasible and could be achieved in comparable parts of the world.

Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790. FINDINGS: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6). INTERPRETATION: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. FUNDING: New South Wales Ministry of Health, Gilead Sciences.

Health promotion 'on steroids': the value of an experiential approach to promote rapid HIV testing in NSW, Australia.

In 2012, there was a sharp increase in human immunodeficiency virus (HIV) notifications in New South Wales (NSW), Australia, following a 10-year period of relative stability. This increase, among other factors, triggered the development of a new HIV strategy that included renewed efforts to increase testing to improve early diagnosis, enable early treatment and reduce the risk of onward transmission. This article describes the activities conducted by NSW Health and partner organisations during November 2013 in the week before World AIDS Day (phase one (P1)) and HIV testing week in July 2014 (phase 2 (P2)). A model of pop-up HIV testing, new to Australia, was used to take testing to those most at risk of infection, and was promoted through social media and experiential techniques. During P1, an average of seven tests per hour were conducted at the pop-up service, compared with four tests per hour at a fast-track screening service in a nearby sexual health clinic. During HIV testing week, the campaign hashtag was mentioned an average of 56 times per day, following a baseline of six mentions per day one week before. The estimated total social media reach was 549,769 people via 459 posts. The pop-up testing model proved popular, and the use of social media and experiential techniques has extended the reach of the 'test more' messages. Further research is required to determine causality between specific HIV messaging and experiential techniques and testing rates.

Lessons learnt from the first Australian 'pop-up' HIV testing site.

Lessons learnt from the first 'pop-up' HIV testing site in Australia suggest that highly visible testing activity was acceptable in the context of inner Sydney and that pop-up sites may be a useful adjunct to clinic-based models. Further evaluation of alternative testing models is needed to inform the scale up of HIV testing in Australia.

A novel time-limited pop-up HIV testing service for gay men in Sydney, Australia, attracts high-risk men.

UNLABELLED: Background HIV diagnoses have been increasing steadily in Australia and are concentrated among gay, bisexual and other men who have sex with men (GBM). HIV testing is a key control strategy, and in 2013, a novel time-limited pop-up community HIV testing service (Pop-up) was introduced to raise awareness and increase testing options for GBM. The Pop-up service offered rapid HIV tests only. We compared uptake and outcomes of the Pop-up service to an established clinical model [a fast-track screening service in a sexual health clinic offering rapid and/or conventional HIV tests and sexually transmissible infection (STI) tests]. METHODS: Service delivery data was collated and analysed from the HIV Pop-up (25 November to 1 December 2013) and the fast-track HIV/STI screening service (Xpress) in a sexual health clinic immediately before the Pop-up (1 August to 22 November 2013). A comparison of all the HIV tests and results, tests per hour and characteristics of new clients (demographics, risk behaviour, testing history) was conducted using χ(2), Poisson distribution and Ranksum tests. RESULTS: At the Pop-up service, 182 GBM had a rapid HIV test conducted over the 5-day period (average: seven HIV tests per hour) and no HIV tests were reactive (0%, 95% confidence interval: 0-1.8%). At the Xpress service, 1075 asymptomatic GBM had at least one STI test and 957 GMB had a HIV test (rapid or conventional) conducted over the 3-month period (average: four HIV tests per hour), with two positive HIV tests (0.2%, 95% confidence interval: 0.02-0.7) and 151 positive STI tests (14%, 95% confidence interval: 12-16.2). Compared with new patients at the Xpress service, GBM attending the Pop-up service were older (median of 39 vs 29 years, P<0.01); more likely to report ≥5 sexual partners in the past 3 months (P=0.02); more likely to reside in 'Gay Sydney' (P<0.01); and more likely to be tested for HIV (P<0.01). CONCLUSIONS: Time-limited Pop-up community HIV testing is feasible and reached high-risk GBM, but compared with a clinic-based model, it only reached a smaller proportion of GBM who test infrequently or who have never been tested and are unaware of their HIV status. No STI testing was conducted through the Pop-up service, which allowed a higher throughput of HIV tests; however, a significant number of STIs may have been missed.