Missed opportunities for guidance on sexually transmitted infection services: a global review of national HIV PrEP guidance.

OBJECTIVES: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income. METHODS: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023. RESULTS: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned. CONCLUSIONS: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

The Future of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: A Global Qualitative Consultation on Provider Perspectives on New Products and Differentiated Service Delivery.

Differentiated service delivery and new products, such as long-acting injectable cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), could increase uptake and use of pre-exposure prophylaxis (PrEP) for HIV prevention. We explored PrEP provider perspectives on differentiated PrEP service delivery and new PrEP products to inform World Health Organization (WHO) guidelines and programme implementation. 150 PrEP providers who participated in a WHO survey were randomly selected and 67 were invited for interviews based on geographic representation, provider cadre, gender, experience with community-based PrEP service delivery, and familiarity with new PrEP products. Semi-structured interviews were conducted virtually. Key themes were inductively extracted relating to differentiated service delivery and benefits and concerns regarding new PrEP products. 30 PrEP providers from 24 countries were interviewed. Across regions, providers were supportive of differentiated service delivery to respond to clients' needs and preferences, maintain services during COVID-19, and ensure access for priority populations that may face access challenges. Providers welcomed prospects of offering CAB-LA to their clients but had concerns about HIV testing, costs, and the need for clinic-based services, including staff who can administer injections. Providers felt the DVR was potentially important for some cisgender women, especially young clients and female sex workers, and raised fewer concerns compared to injectable PrEP. Providers' views are critical for the development of guidelines and implementing programmes that will best serve PrEP users. Understanding areas where provider capacities and biases may create barriers can define opportunities for training and support to ensure that providers can deliver effective programmes.

Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs: a global mapping of service delivery.

BACKGROUND: The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. METHODS: Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. RESULTS: PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. CONCLUSIONS: This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

Ending AIDS in the Asia-Pacific region by 2030: are we on track? Policy, epidemiological and intervention insights.

The Asia-Pacific region is home to nearly 6 million people living with HIV. Across the region, key populations - men who have sex with men, transgender women, people who inject drugs, sex workers, prisoners - and their sexual partners make up the majority of those living with HIV. While significant progress has been made in the past 5 years towards UNAIDS's 90-90-90 goals (90% of people with HIV diagnosed, 90% on antiretroviral therapy, 90% virologically suppressed), significant gaps remain. The papers in this Special Issue address important questions: are we on track to end the AIDS epidemic in the Asia-Pacific region? And can countries in this region reach the new UNAIDS targets for 2030?

Rising Chlamydia and Gonorrhoea Incidence and Associated Risk Factors Among Female Sex Workers in Australia: A Retrospective Cohort Study.

BACKGROUND: Female sex workers in Australia have achieved some of the lowest documented prevalences of human immunodeficiency virus (HIV) and other sexually transmissible infections globally but rates overall are increasing in Australia and warrant closer investigation. METHODS: We constructed a retrospective cohort using repeat testing data extracted from a network of 42 sexual health clinics. Poisson and Cox regression were used to determined trends in incidence and risk factors for HIV, chlamydia, gonorrhoea, and infectious syphilis among female sex workers. RESULTS: From 2009 to 2015, 18,475 women reporting sex work attended a participating service. The overall incidence of urogenital chlamydia was 7.7/100 person years (PY), declining by 38% from 2009 to 2013 before increasing by 43% to 2015 (P < 0.001); anorectal chlamydia incidence was 0.6/100 PY, and pharyngeal was 1.9/100 PY, which increased significantly during the study period (P < 0.001, both). For gonorrhoea, the urogenital incidence was 1.4/100 PY, anorectal incidence was 0.3/100 PY, P < 0.001), and 3.6/100 PY for pharyngeal; urogenital incidence doubled during the study period, anorectal increased fivefold, and pharyngeal more than tripled (P < 0.001, all). Incidence of infectious syphilis was 0.4/100 PY, which remained stable from 2009 to 2015 (P = 0.09). There were seven incident infections of HIV among female sex workers (0.1/100 PY). Inconsistent condom use with private partners, higher number of private partner numbers, recent injecting drug use, younger age, and country of birth variously predicted sexually transmissible infections among female sex workers. CONCLUSIONS: Although infectious syphilis and HIV remain uncommon in female sex workers attending Australian sexual health clinics, the increasing incidence of gonorrhoea across anatomical sites and increasing chlamydia after a period of decline demands enhanced health promotion initiatives.

Shaping and coordinating the implementation science agenda for injectable cabotegravir for PrEP: the role of the Biomedical Prevention Implementation Collaborative (BioPIC).

INTRODUCTION: Data from two randomized controlled trials (RCTs) showed that injectable cabotegravir (CAB) for pre-exposure prophylaxis (PrEP) was efficacious in reducing HIV acquisition. The US Food and Drug Administration approved CAB for PrEP in December 2021; Australia in August 2022; Zimbabwe in October 2022; South Africa in November 2022; Malawi in March 2023; and regulatory approvals are being sought in additional countries. The World Health Organization (WHO) recommended CAB be offered to people at substantial risk of HIV in July 2022. However, implementation experience beyond RCTs is limited. As countries consider CAB implementation, questions remain regarding delivery and involvement of populations excluded from the trials. A coordinated approach is needed to ensure these are addressed and CAB can be introduced in low- and middle-income countries in timely, acceptable and effective ways. DISCUSSION: Beginning in 2018, the Biomedical Prevention Implementation Collaborative (BioPIC) convened over 100 global health experts to develop a comprehensive introduction strategy for CAB. Using this roadmap, country landscaping for CAB introduction and lessons from oral PrEP implementation, AVAC and WHO co-convened 50 researchers, donors, implementers and civil society in September 2021 to: (1) identify questions and evidence gaps related to CAB across contexts and partners; (2) define the implementation science agenda; and (3) agree on mechanism(s) for future coordination. As a result, CAB-related questions were identified, including: defining optimal and feasible HIV testing strategies that expand access; delivery models; integration with a range of services, including family planning and antenatal care; and embedding CAB in demand generation for HIV prevention choices. Through convenings and mapping of implementation research, BioPIC identified gaps in populations, geographies and delivery approaches. CONCLUSIONS: The introduction strategy refined by BioPIC lays the groundwork for future HIV prevention products. Ongoing policy and implementation dialogue is critical to accelerate the design of CAB implementation studies that adequately address priority knowledge gaps. Additional long-acting HIV prevention products may be available over the next 5 years, increasing choice, but potentially making delivery and stakeholder engagement more complex. Ongoing coordination with WHO will accelerate the adoption of evidence-based policies and wide-scale implementation, and lessons from BioPIC can inform introduction processes for long-acting HIV prevention products.

Systematic review of the values and preferences regarding the use of injectable pre-exposure prophylaxis to prevent HIV acquisition.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an important HIV prevention option. Two randomized trials have provided efficacy evidence for long-acting injectable cabotegravir (CAB-LA) as PrEP. In considering CAB-LA as an additional PrEP modality for people at substantial risk of HIV, it is important to understand community response to injectable PrEP. We conducted a systematic review of values, preferences and perceptions of acceptability for injectable PrEP to inform global guidance. METHODS: We searched nine databases and conference websites for peer-reviewed and grey literature (January 2010-September 2021). There were no restrictions on location. A two-stage review process assessed references against eligibility criteria. Data from included studies were organized by constructs from the Theoretical Framework of Acceptability. RESULTS: We included 62 unique references. Most studies were observational, cross-sectional and qualitative. Over half of the studies were conducted in North America. Men who have sex with men were the most researched group. Most studies (57/62) examined injectable PrEP, including hypothetical injectables (55/57) or placebo products (2/57). Six studies examined CAB-LA specifically. There was overall interest in and often a preference for injectable PrEP, though there was variation within and across groups and regions. Many stakeholders indicated that injectable PrEP could help address adherence challenges associated with daily or on-demand dosing for oral PrEP and may be a better lifestyle fit for individuals seeking privacy, discretion and infrequent dosing. End-users reported concerns, including fear of needles, injection site pain and body location, logistical challenges and waning or incomplete protection. DISCUSSION: Despite an overall preference for injectable PrEP, heterogeneity across groups and regions highlights the importance of enabling end-users to choose a PrEP modality that supports effective use. Like other products, preference for injectable PrEP may change over time and end-users may switch between prevention options. There will be a greater understanding of enacted preference as more end-users are offered anti-retroviral (ARV)-containing injectables. Future research should focus on equitable implementation, including real-time decision-making and how trained healthcare providers can support choice. CONCLUSIONS: Given overall acceptability, injectable PrEP should be included as part of a menu of prevention options, allowing end-users to select the modality that suits their preferences, needs and lifestyle.

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

OBJECTIVE: HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines. DESIGN: Systematic review and meta-analysis. METHODS: We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resistance, pregnancy-related adverse events, and sexual behavior. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively. RESULTS: We identified 12 articles/abstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval: 0.07-0.61), resulting in a 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior. CONCLUSIONS: CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies; more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials.

Scaling up access to HIV pre-exposure prophylaxis (PrEP): should nurses do the job?

Task sharing has been one of the most important enabling policies supporting the global expansion of access to HIV testing and treatment. The WHO public health approach, which relies on delivery of antiretroviral therapy (ART) by nurses, has enabled a trebling of the number of people receiving ART during the past decade. WHO recognises that HIV pre-exposure prophylaxis (PrEP) can also be provided by nurses; however, many countries still do not have policies in place that support nurse provision of PrEP. In sub-Saharan Africa, most countries allow nurses to prescribe ART, but only a few countries have policies in place that allow nurses to prescribe PrEP. Nurse-led PrEP delivery is particularly low in the Asia-Pacific region, which has some of the world's fastest growing epidemics. Even in many high-income countries, PrEP scale-up has been limited because policies often require medical doctors or specialists to prescribe. Service providers in many countries are coming to realise that scaling up access to PrEP cannot be achieved by medical doctors alone, and nurse-led PrEP delivery can help to lay the groundwork for supporting uptake of other HIV prevention approaches that will become available in the future. Countries with policies that authorise nurses to prescribe ART could be early adopters and help to pave the way for wider adoption of nurse-led PrEP delivery.

Cost-effectiveness and impact of pre-exposure prophylaxis to prevent HIV among men who have sex with men in Asia: A modelling study.

INTRODUCTION: More than 70% of new HIV infections in Asia occurred in eight countries in 2020: Cambodia, China, India, Indonesia, Myanmar, Nepal, Thailand, and Vietnam-with a rising incidence among men who have sex with men (MSM). The World Health Organization (WHO) recommends pre-exposure prophylaxis (PrEP) for those at risk of acquiring HIV, yet wide-scale implementation of PrEP, on a daily or event-driven basis, has been limited in Asia. METHODS: The Optima HIV model was applied to examine the impact of scaling-up PrEP over five-years to cover an additional 15% of MSM compared with baseline coverage, a target deemed feasible by regional experts. Based on behavioral survey data, we assume that covering 15% of higher-risk MSM will cover 30% of all sexual acts in this group. Scenarios to compare the impact of generic-brand daily dosing of PrEP with generic event-driven dosing (15 days a month) were modelled from the start of 2022 to the end of 2026. Cost-effectiveness of generic versus branded PrEP was also assessed for China, the only country with an active patent for branded, higher cost PrEP. The impact on new HIV infections among the entire population and cost per HIV-related disability-adjusted life year (DALY) averted were estimated from the beginning of 2022 to the end of 2031 and from 2022 to 2051. RESULTS: If PrEP were scaled-up to cover an additional 15% of MSM engaging in higher-risk behavior from the beginning of 2022 to the end of 2026 in the eight Asian countries considered, an additional 100,000 (66,000-130,000) HIV infections (17%) and 300,000 (198,000-390,000) HIV-related DALYs (3%) could be averted over the 2022 to 2031 period. The estimated cost per HIV-related DALY averted from 2022 to 2031 ranged from US$600 for event-driven generic PrEP in Indonesia to US$34,400 for daily branded PrEP in Thailand. Over a longer timeframe from 2022 to 2051, the cost per HIV-related DALY averted could be reduced to US$100-US$12,700. CONCLUSION: PrEP is a critical tool to further reduce HIV incidence in highly concentrated epidemics. Implementing PrEP in Asia may be cost-effective in settings with increasing HIV prevalence among MSM and if PrEP drug costs can be reduced, PrEP could be more cost-effective over longer timeframes.

Variation in human genetic polymorphisms, their association with Helicobacter pylori acquisition and gastric cancer in a multi-ethnic country.

BACKGROUND AND AIM: The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients. METHODS: Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models. RESULT: The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection. CONCLUSION: These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection.

Adoption of guidelines on and use of oral pre-exposure prophylaxis: a global summary and forecasting study.

BACKGROUND: In 2016, the UN General Assembly set a global target of 3 million oral pre-exposure prophylaxis (PrEP) users by 2020. With this target at an end, we aimed to assess global trends in the adoption of WHO PrEP recommendations into national guidelines and numbers of PrEP users, defined as people who received oral PrEP at least once in a given year, and to estimate future trajectories of PrEP use. METHODS: In this global summary and forecasting study, data on adoption of WHO PrEP recommendations and numbers of PrEP users were obtained through the Global AIDS Monitoring system and WHO regional offices. Trends in these indicators for 2016-19 by region and for 2019 by country were described, including by gender and priority populations where data were available. PrEP user numbers were forecasted until 2023 by selecting countries with at least 3 years of PrEP user data as example countries in each region to represent possible future PrEP user trajectories. PrEP user growth rates observed in example countries were applied to countries in corresponding regions under different scenarios, including a COVID-19 disruption scenario with static global PrEP use in 2020. FINDINGS: By the end of 2019, 120 (67%) of 180 countries with data had adopted the WHO PrEP recommendations into national guidelines (23 in 2019 and 30 in 2018). In 2019, there were about 626 000 PrEP users across 77 countries, including 260 000 (41·6%) in the region of the Americas and 213 000 (34·0%) in the African region; this is a 69% increase from about 370 000 PrEP users across 66 countries in 2018. Without COVID-19 disruptions, 0·9-1·1 million global PrEP users were projected by the end of 2020 and 2·4-5·3 million are projected by the end of 2023. If COVID-19 disruptions resulted in no PrEP user growth in 2020, the projected number of PrEP users in 2023 is 2·1-3·0 million. INTERPRETATION: Widespread adoption of WHO PrEP recommendations coincided with a global increase in PrEP use. Although the 2020 global PrEP target will be missed, strong future growth in PrEP use is possible. New PrEP products could expand the PrEP user base, and, with greater expansion of oral PrEP, further adoption of WHO PrEP recommendations, and simplified delivery, PrEP could contribute to ending AIDS by 2030. FUNDING: Unitaid, Bill & Melinda Gates Foundation, and WHO.

Distinct cagA EPIYA motifs are associated with ethnic diversity in Malaysia and Singapore.

BACKGROUND: In vitro studies have shown that the biologic activity of CagA is influenced by the number and class of EPIYA motifs present in its variable region as these motifs correspond to the CagA phosphorylation sites. It has been hypothesized that strains possessing specific combinations of these motifs may be responsible for gastric cancer development. This study investigated the prevalence of cagA and the EPIYA motifs with regard to number, class, and patterns in strains from the three major ethnic groups within the Malaysian and Singaporean populations in relation to disease development. MATERIALS AND METHODS: Helicobacter pylori isolates from 49 Chinese, 43 Indian, and 14 Malay patients with functional dyspepsia (FD) and 21 gastric cancer (GC) cases were analyzed using polymerase chain reaction for the presence of cagA and the number, type, and pattern of EPIYA motifs. Additionally, the EPIYA motifs of 47 isolates were sequenced. RESULTS: All 126 isolates possessed cagA, with the majority encoding EPIYA-A (97.6%) and all encoding EPIYA-B. However, while the cagA of 93.0% of Indian FD isolates encoded EPIYA-C as the third motif, 91.8% of Chinese FD isolates and 81.7% of Chinese GC isolates encoded EPIYA-D (p < .001). Of Malay FD isolates, 61.5% and 38.5% possessed EPIYA-C and EPIYA-D, respectively. The majority of isolates possessed three EPIYA motifs; however, Indian isolates were significantly more likely to have four or more (p < .05). CONCLUSION: Although, H. pylori strains with distinct cagA-types are circulating within the primary ethnic groups resident in Malaysia and Singapore, these genotypes appear unassociated with the development of GC in the ethnic Chinese population. The phenomenon of distinct strains circulating within different ethnic groups, in combination with host and certain environmental factors, may help to explain the rates of GC development in Malaysia.

A priority-driven, policy-relevant research program to support a response to blood-borne viruses and sexually transmissible infections in NSW, Australia.

OBJECTIVES: Strong collaboration between researchers, policy makers and practitioners supports the use of research evidence in policy and practice. Strategies for increasing the use of evidence in policy development and implementation include creating more opportunities for closer collaboration between researchers and policy makers, ensuring research syntheses are more accessible to policy makers, and increasing workforce capacity to utilise evidence. Type of program or service: The BBV & STI Research, Intervention and Strategic Evaluation Program, 2014-2019 (BRISE) is a coherent and integrated program that delivers policy-relevant research, strategic advice, capacity building and communications to support the response to blood-borne viruses (BBV) and sexually transmissible infections (STI) in New South Wales (NSW), Australia. BRISE has five key objectives: generate high-quality research; maximise the use of research; build research capacity; communication and marketing; and governance and management. RESULTS: BRISE facilitates the coproduction of research where researchers and policy makers are meaningfully involved in all stages of research priority setting and codesign from development to application, building an understanding of the way evidence is generated to allow for greater integration between research and use of evidence. LESSONS LEARNT: Bringing multiple research projects together under a single contract and budget provided the NSW Ministry of Health (the Ministry) with cost efficiencies and streamlined contract management and project reporting. A flexible work plan allowed for a mix of longer-term (up to 5-year) projects and shorter projects that were responsive to emerging policy-relevant research priorities. The Ministry became involved in the production of collaborative research as a research partner, rather than solely a research 'funder'. The joint management of research projects involving a policy officer from the Ministry provided opportunities for individuals to build on their research capabilities and literacy. Collaborative priority setting and project work, and increased research literacy, improved the likelihood that research generated would then be used in policy and practice.

Nurse-led pre-exposure prophylaxis: a non-traditional model to provide HIV prevention in a resource-constrained, pragmatic clinical trial.

There is little evidence and no standardised model for nurse-led HIV pre-exposure prophylaxis (PrEP). In 2016, public sexual health clinics in the state of New South Wales (NSW), Australia, participating in the population-scale PrEP access trial Expanded PrEP Implementation In Communities in New South Wales (EPIC-NSW) were authorised to adopt a nurse-led model of PrEP provision in order to facilitate the rapid expansion of PrEP access to more than 8000 participants in under 2 years without additional resources. The model has been implemented successfully in public clinics in 10 of 14 local health districts, with widespread support and no serious safety events reported. With the increasing importance of PrEP as an HIV prevention tool, non-traditional models of care, including nurse-led PrEP, are needed.

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.