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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., Competing Interests: Potential conflicts of interest. N. J. D. has received research support through the Gilead Australia Fellowship for an unrelated project (paid to institution). A. C. has received research funding from Gilead Sciences, MSD, and ViiV Healthcare (paid to institution); consulting fees, lecture and travel sponsorships from Gilead Sciences, MSD. and ViiV Healthcare (paid to author); and has served on advisory boards for Gilead Sciences, MSD. and ViiV Healthcare (paid to author). I. Z. has received previous research support from Gilead Sciences for research unrelated to the current work and is a member of the Australian Nation PrEP Guideline Writing Group. P. R. has received research funding from Gilead Sciences, and honoraria for speaking from Gilead Sciences, MSD, and ViiV. B. B. reports grants from Gilead Sciences (Unrestricted research grant, 2021-22) and ViiV Healthcare (Unrestricted research grant, 2022-23), honorarium from Gilead Sciences (speakers fee, 2020), and support from ViiV Healthcare (Travel to Melbourne for meeting, 2022). A. E. G. reports royalties or licenses from ViiV, implementation research on injectable PrEP (paid to institution), support from ViiV for attending a meeting on injectable treatment (2022) and is a member of the Governing council of the International AIDS society. R. G. is an investigator on a project that receives funding from Gilead (unrelated to this project). J. H. is an executive member for the board at NSW Gender Centre inc. S. J. M. reports support from Gilead to attend local education evenings (does not include national or international meetings; unpaid participation, local restaurant dinner and talk). B. Y. reports support from Mylan Pty Ltd (travelled to Canberra, Australian Capital Territory to present EPIC-NSW study at a clinical care meeting at Canberra Hospital on 28 August 2019). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The use of preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has raised concerns of increased sexual risk behaviors. These behaviors may be associated with increased incidence of sexually acquired hepatitis C virus (HCV) among gay and bisexual men., Methods: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study was a cohort study of daily coformulated tenofovir disoproxil fumarate and emtricitabine for HIV prevention. We recruited 9596 people at high risk of HIV acquisition from 31 clinics across New South Wales and the Australia Capital Territory in Australia. We report prior exposure to HCV and incidence in this cohort between 2016 and 2019., Results: At least 1 HCV test result was available for 8658 (90.2%) participants. These individuals had a median age of 34 years (interquartile range, 28-43), most of whom were male (8530, 98.5%), identified as gay (7944, 91.8%), and were born in Australia (51.8%). Prior exposure to HCV was detected among 81 participants at baseline (0.9%; 95% confidence interval [CI]: .71.2). Twenty of 8577 participants were diagnosed with incident infection (rate 0.2/100 person-years [95% CI: .1-.3/100 person-years]). They were significantly older (median age 41 years vs 34 years, P = .044), and more likely to report methamphetamine use at baseline (incidence rate ratio, 2.7 [95% CI: 1.00-7.2]) than those without incident infection., Conclusions: In this population of PrEP users, HCV prior exposure and incidence were low. With high levels of HCV and HIV testing and treatment, the dual goals of HIV and HCV elimination could be achieved in this population. Clinical Trials Registration: number NCT02870790., Competing Interests: Potential conflicts of interest. A. G. receives grant funding from Viiv for study of injectable preexposure prophylaxis and Seqirus for genital warts surveillance; membership of global forum on adult HPV from MSD; member of Governing Council 2020 from International AIDS Society; and in kind support for a trial of a gonorrhea vaccine (Bexsero vaccine) from GSK. B. B. receives unrestricted grant funding from ViiV and Gilead Sciences for studies unrelated to the submitted work, 2021–2022; travel honorarium in 2019 from Gilead Sciences; honorarium in 2020 from Gilead Sciences and honorarium in 2021 from Virology Education; and Board Director of HIV communication organization in NSW Australia from ACON Health. G. M, receives grant funding from Gilead Sciences and AbbVie and reports payment or honoraria from Janssen. N. D. received research support paid to her institution (UNSW Sydney) through a Gilead Australia Fellowship for an unrelated project. P. R. receives from funding from Gilead Sciences and personal speaker fees from Gilead Sciences and AbbVie. D. J. T. has received payment for providing expert reports for the NSW justice system on the significance of STIs in cases of suspected child sexual abuse. He has not received payment for expert testimony relevant to any aspect of this manuscript on PrEP more generally. D. A. B. reports trial funding from Viiv Healthcare and MSD; participation on an Advisory Board for Gilead Sciences and AbbVie; and a leadership or fiduciary role as an advisor to Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). No other investigators reported any other relevant funding or conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: HIV preexposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations., Methods: A posthoc analysis of EPIC-NSW, a large Australian multicentre PrEP implementation trial for patients at high risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new-onset renal impairment, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2., Results: A total of 6808 participants were eligible for inclusion. Almost all were male (99%), with a median age of 35 years [interquartile range (IQR): 28-44]. Approximately one-quarter (26%) had a baseline eGFR <90 ml/min per 1.73 m2. Over a median follow-up period of 1.2 years (IQR: 0.6-1.7), the rate of renal impairment was 5.8 episodes per 1000 person-years [95% confidence interval (CI): 4.0-7.8]. In multivariable Cox regression, there was a higher risk of renal impairment in participants aged ≥50 years [hazard ratio (HR) 14.7, 95% CI: 5.0-43.3, P < 0.001] and those with an eGFR <90 ml/min per 1.73 m2 (HR 28.9, 95% CI: 6.9-121.9) at baseline., Conclusion: In a large-scale implementation study, TDF-containing PrEP was associated with a low risk of renal impairment overall, whereas older patients and those with preexisting renal dysfunction were at substantially increased risk., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background In Australia, the preventative use of antiretroviral drugs [pre-exposure prophylaxis (PrEP) and treatment as prevention] is being embraced to protect individuals at high risk of HIV and reduce onward transmission., Methods: The adaptation of a behavioural surveillance system, the Gay Community Periodic Surveys, was reviewed to monitor the uptake and effect of new prevention strategies in Australia's primary HIV-affected population (gay and bisexual men, GBM). The national trends in key indicators during 2000-15 were reviewed and a new measure to take account of antiretroviral-based prevention was developed., Results: Between 2000 and 2015, there were significant increases (P<0.001) in annual HIV testing (56.1-64.8%), condomless sex with casual partners (26.8-38.8%) and the proportion of HIV-positive men on HIV treatment (72.5-88.4%) and with an undetectable viral load (73.7-94.7%). The proportion of casual partners who were HIV negative, not on PrEP and who engaged in receptive condomless sex also increased between 2000 and 2015 from 12.8 to 19.3%. Two scenarios anticipating the effect of PrEP highlighted the need to target GBM who engage in receptive condomless sex while also sustaining condom use at a population level., Conclusions: Behavioural surveillance can be successfully adapted to follow the effect of antiretroviral-based prevention. It is anticipated that HIV testing and HIV treatment will continue to increase among Australian GBM, but to prevent new infections, intervention in the growing proportion of GBM who have condomless sex with casual partners is needed. For PrEP to have its desired effect, condom use needs to be sustained.

Introduction: HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers., Discussion: Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific., Conclusions: Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes., Competing Interests: IZ and AG have received research funding and in-kind supply of study medication (Truvada) from Gilead Sciences, Inc. NP, TA, SJ and YRL have no conflict of interest to declare.

Introduction: Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults., Methods and Analysis: PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants-mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV., Ethics and Dissemination: The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete., Trial Registration Number: NCT02206555; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We analyzed the HIV risk reduction strategies (RRS) used by Australian gay and bisexual men with casual partners. Among 1346 men who reported any condomless anal intercourse with casual partners, 75% frequently practiced at least one RRS. The most common RRS was serosorting, frequently practiced by 55% of HIV-positive and 47% of HIV-negative participants. Condoms were frequently (but inconsistently) used by 17% of HIV-positive, 41% of HIV-negative, and 30% of untested participants. Relying on an undetectable viral load was frequently practiced by 58% of HIV-positive participants. Strategic positioning, withdrawal, and non-HIV-positive men taking antiretroviral medication were less common strategies.

Purpose of Review: HIV infection among MSM remains a significant issue. Data relevant to MSM populations from animal models, pharmacokinetic studies and clinical trials are summarized and challenges and potential consequences of use of preexposure prophylaxis (PrEP) by MSM are discussed., Recent Findings: Rectal simian-human immunodeficiency virus transmission in macaque models can be prevented by intermittent PrEP dosing. The Preexposure Prophylaxis Initiative (iPrEx) study found that daily oral emtricitabine-tenofovir disoproxyl fumarate (TDF/FTC) decreased HIV infection by 44% among 2499 high-risk MSM. Men with detectable levels of TDF or FTC in plasma and peripheral blood mononuclear cells experienced more than 90% protective effect, emphasizing the importance of adherence. In iPrEX and other studies, PrEP was generally safe and well tolerated. However, it appears that TDF use is associated with a small but significant decrease in mean bone mineral density. No risk compensation has been demonstrated, but this remains an area of potential concern when PrEP is used outside the setting of a placebo-controlled trial. Numerous PrEP trials in MSM are currently underway., Summary: Oral FTC/TDF is effective in preventing HIV infection among MSM. Optimal PrEP agents and dosing regimens now need to be identified. Understanding the patterns of and impediments to PrEP use among MSM is vital and these should be monitored in ongoing demonstration projects and open-label studies.

Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006., Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts., Results: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community-based surveys in Australia (69-85% and 49-83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small., Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.