Client and staff perceptions of acceptability of MyCheck: a direct-to-pathology telehealth and e-testing service for comprehensive bloodborne virus and sexually transmissible infection screening.

Background Sydney Sexual Health Centre (SSHC) is the largest sexual health clinic in New South Wales (NSW), servicing clients at high risk of sexually transmissible infections and bloodborne viruses. SSHC piloted a direct-to-pathology pathway that facilitated bloodborne virus/sexually transmissible infection testing at one of the ~500 participating pathology collection centres located across NSW. This qualitative study sought to understand SSHC client and provider perspectives of acceptability of the MyCheck intervention. Methods Semi-structured in-depth interviews were conducted with 11 clients who underwent testing via the MyCheck pathway and eight staff members involved in implementing MyCheck. The seven components of Sekhon's Theoretical Framework of Acceptability informed this analysis. Results Participants broadly conveyed 'affective attitude' toward the MyCheck pathway. The telehealth intervention reduced client 'burden' and 'opportunity cost' through enabling greater testing convenience at a location suitable to them and provided timely results. Issues of 'ethicality' were raised by clients and staff as pathology centre staff were, on a few occasions, regarded as being judgmental of SSHC clients. 'Intervention coherence' issues were largely attributed to pathology centre personnel being unfamiliar with the intervention, with billing issues being a recurrent concern. Participants perceived MyCheck as an 'effective' testing pathway. SSHC staff were able to offer the intervention with ease through seamless IT integration ('self-efficacy'). Conclusion The MyCheck intervention was perceived by both SSHC clients and staff as an acceptable bloodborne virus/sexually transmissible infection testing pathway. However, further work is required to address stigma experienced by some clients when attending pathology collection centres.

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand - the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM).

Recent studies have provided evidence for the effectiveness of using doxycycline (Doxy-PEP) to prevent bacterial sexually transmissible infections (STI), namely chlamydia, gonorrhoea, and syphilis, among gay, bisexual, and other men who have sex with men who have experienced multiple STIs. However, there remain several unanswered questions around potential adverse outcomes from Doxy-PEP, including the possibility of inducing antimicrobial resistance in STIs and other organisms, and the possibility of disrupting the microbiome of people who choose to use Doxy-PEP. This interim position statement from the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine aims to outline the current evidence for Doxy-PEP, and to highlight potential adverse outcomes, to enable clinicians to conduct evidence-based conversations with patients in Australia and Aotearoa New Zealand who intend to use Doxy-PEP.

Infectious syphilis in women and heterosexual men in major Australian cities: sentinel surveillance data, 2011-2019.

OBJECTIVES: To examine changes in the positive infectious syphilis test rate among women and heterosexual men in major Australian cities, and rate differences by social, biomedical, and behavioural determinants of health. DESIGN, SETTING: Analysis of data extracted from de-identified patient records from 34 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses (ACCESS). PARTICIPANTS: First tests during calendar year for women and heterosexual men aged 15 years or more in major cities who attended ACCESS sexual health clinics during 2011-2019. MAIN OUTCOME MEASURES: Positive infectious syphilis test rate; change in annual positive test rate. RESULTS: 180 of 52 221 tested women (0.34%) and 239 of 36 341 heterosexual men (0.66%) were diagnosed with infectious syphilis. The positive test rate for women was 1.8 (95% confidence interval [CI], 0.9-3.2) per 1000 tests in 2011, 3.0 (95% CI, 2.0-4.2) per 1000 tests in 2019 (change per year: rate ratio [RR], 1.12; 95% CI, 1.01-1.25); for heterosexual men it was 6.1 (95% CI, 3.8-9.2) per 1000 tests in 2011 and 7.6 (95% CI, 5.6-10) per 1000 tests in 2019 (RR, 1.10; 95% CI, 1.03-1.17). In multivariable analyses, the positive test rate was higher for women (adjusted RR [aRR], 1.85; 95% CI, 1.34-2.55) and heterosexual men (aRR, 2.39; 95% CI, 1.53-3.74) in areas of greatest socio-economic disadvantage than for those in areas of least socio-economic disadvantage. It was also higher for Indigenous women (aRR, 2.39; 95% CI, 1.22-4.70) and for women who reported recent injection drug use (aRR, 4.87; 95% CI, 2.18-10.9) than for other women; it was lower for bisexual than heterosexual women (aRR, 0.48; 95% CI, 0.29-0.81) and for women who reported recent sex work (aRR, 0.35; 95% CI, 0.29-0.44). The positive test rate was higher for heterosexual men aged 40-49 years (aRR, 2.11; 95% CI, 1.42-3.12) or more than 50 years (aRR, 2.36; 95% CI, 1.53-3.65) than for those aged 15-29 years. CONCLUSION: The positive test rate among both urban women and heterosexual men tested was higher in 2019 than in 2011. People who attend reproductive health or alcohol and drug services should be routinely screened for syphilis.

Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is associated with adverse renal outcomes when prescribed for HIV infection. There are few data concerning real-world renal outcomes amongst patients prescribed TDF for pre-exposure prophylaxis (PrEP). METHODS AND FINDINGS: Data were extracted from 52 sexual health clinics across Australia from 2009-2019. All patients prescribed TDF-containing antiretroviral therapy and PrEP were included. Rates of renal impairment (a fall in eGFR to <60 ml/min/1·73m2) were calculated for people living with HIV (PLWHIV) prescribed TDF and HIV negative PrEP-users. Risk factors were assessed using Cox-proportional hazards models. Sensitivity analysis of risk using 1:1 propensity-score matching to adjust for potential imbalance in HIV and PrEP cohorts was conducted. 5,973 patients on PrEP and 1,973 PLWHIV were included. There were 39 (0.7%) instances of renal impairment in the PrEP group and 81 (4.1%) in the PLWHIV cohort (hazard ratio [HR]:0.35 95% confidence interval [CI]: 0.22-0.56). Rates of renal impairment were 4.01/1000 person-years (95%CI:2.93-5.48) in the PrEP cohort and 16.18/1000 person-years (95%CI:13.01-20.11) in the PLWHIV cohort (p<0.001). Predictors of renal impairment were: older age (40-49 years (HR:5.09 95%CI: 2.12-12.17) and 50-82 years (HR:13.69 95%CI: 5.92-31.67) (compared with 30-39 years) and baseline eGFR<90ml/min (HR:61.19 95%CI: 19.27-194.30). After adjusting for age and baseline eGFR the rate of renal impairment remained lower in the PrEP cohort (aHR:0.62 95%CI: 0.40-0.94, p = 0.023). In propensity-matched analysis using 1,622 patients per cohort the risk of renal impairment remained higher in the PLWHIV cohort (log-rank p = 0.001). CONCLUSION: Patients prescribed TDF-based PrEP had lower rates of renal impairment than patients prescribed TDF for HIV infection. In propensity analysis, after matching for some risk factors, rates of renal impairment remained higher amongst patients with HIV.

Australian sexually transmitted infection (STI) management guidelines for use in primary care 2022 update.

The 'Australian Sexually Transmitted Infection (STI) Management Guidelines For Use In Primary Care' (www.sti.guidelines.org.au ) provide evidence-based, up-to-date guidance targeted at use in primary care settings. A major review of the guidelines was undertaken in 2020-22. All content was reviewed and updated by a multi-disciplinary group of clinical and non-clinical experts, and assessed for appropriateness of recommendations for key affected populations and organisational and jurisdictional suitability. The guidelines are divided into six main sections: (1) standard asymptomatic check-up; (2) sexual history; (3) contact tracing; (4) STIs and infections associated with sex; (5) STI syndromes; and (6) populations and situations. This paper highlights important aspects of the guidelines and provides the rationale for significant changes made during this major review process.

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.

Long-term protection from HIV infection with oral HIV pre-exposure prophylaxis in gay and bisexual men: findings from the expanded and extended EPIC-NSW prospective implementation study.

BACKGROUND: Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. METHODS: Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790. FINDINGS: Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44). INTERPRETATION: HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk. FUNDING: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.

Young Aboriginal people's sexual health risk reduction strategies: a qualitative study in remote Australia.

Background Surveillance data indicate that Aboriginal and Torres Strait Islander young people are more likely than their non-Indigenous counterparts to experience sexually transmissible infections (STIs) and teenage pregnancy. Despite increasing emphasis on the need for strengths-based approaches to Aboriginal sexual health, limited published data document how young Aboriginal people reduce sexual health risks encountered in their everyday lives. METHODS: In-depth interviews with 35 young Aboriginal women and men aged 16-21 years in two remote Australian settings were conducted; inductive thematic analysis examining sexual health risk reduction practices was also conducted. RESULTS: Participants reported individual and collective STI and pregnancy risk reduction strategies. Individual practices included accessing and carrying condoms; having a regular casual sexual partner; being in a long-term trusting relationship; using long-acting reversible contraception; having fewer sexual partners; abstaining from sex; accessing STI testing. More collective strategies included: refusing sex without a condom; accompanied health clinic visits with a trusted individual; encouraging friends to use condoms and go for STI testing; providing friends with condoms. CONCLUSION: Findings broaden understanding of young Aboriginal people's sexual health risk reduction strategies in remote Aboriginal communities. Findings signal the need for multisectoral STI prevention and sexual health programs driven by young people's existing harm minimisation strategies and cultural models of collective support. Specific strategies to enhance young people's sexual health include: peer condom distribution; accompanied health service visits; peer-led health promotion; continued community-based condom distribution; enhanced access to a fuller range of available contraception in primary care settings; engaging health service-experienced young people as 'youth health workers'.

Outreach services to brothels facilitate sexually transmissible infection testing for Asian sex workers in regional Australia.

Outreach services providing sexually transmissible infection (STI) testing on-site in brothels were introduced in 2012 by Pacific Clinic Newcastle, Australia. Asian female sex workers (FSW) were more likely than non-culturally and linguistically diverse (CALD) FSW to access testing via outreach services than in clinics (OR 2.38, 95% CI 1.82-3.11, P < 0.0001) and to test positive for chlamydia or gonorrhoea (OR 2.58, 95% CI 1.58-4.20, P = 0.0001). Outreach services offering testing on-site in brothels are recommended to facilitate access for Asian FSW in similar settings.

Young Aboriginal people's engagement with STI testing in the Northern Territory, Australia.

BACKGROUND: Australian surveillance data document higher rates of sexually transmissible infections (STIs) among young Aboriginal people (15-29 years) in remote settings than non-Aboriginal young people. Epidemiological data indicate a substantial number of young Aboriginal people do not test for STIs. Rigorous qualitative research can enhance understanding of these findings. This paper documents socio-ecological factors influencing young Aboriginal people's engagement with clinic-based STI testing in two remote settings in the Northern Territory, Australia. METHODS: In-depth interviews with 35 young Aboriginal men and women aged 16-21 years; thematic analysis examining their perceptions and personal experiences of access to clinic-based STI testing. RESULTS: Findings reveal individual, social and health service level influences on willingness to undertake clinic-based STI testing. Individual level barriers included limited knowledge about asymptomatic STIs, attitudinal barriers against testing for symptomatic STIs, and lack of skills to communicate about STIs with health service staff. Social influences both promoted and inhibited STI testing. In setting 1, local social networks enabled intergenerational learning about sexual health and facilitated accompanied visits to health clinics for young women. In setting 2, however, social connectedness inhibited access to STI testing services. Being seen at clinics was perceived to lead to stigmatisation among peers and fear of reputational damage due to STI-related rumours. Modalities of health service provision both enhanced and inhibited STI testing. In setting 1, outreach strategies by male health workers provided young Aboriginal men with opportunities to learn about sexual health, initiate trusting relationships with clinic staff, and gain access to clinics. In setting 2, barriers were created by the location and visibility of the clinic, appointment procedures, waiting rooms and waiting times. Where inhibitive factors at the individual, social and health service levels exist, young Aboriginal people reported more limited access to STI testing. CONCLUSIONS: This is the first socio-ecological analysis of factors influencing young Aboriginal people's willingness to undertake testing for STIs within clinics in Australia. Strategies to improve uptake of STI testing must tackle the overlapping social and health service factors that discourage young people from seeking sexual health support. Much can be learned from young people's lived sexual health experiences and family- and community-based health promotion practices.

Computationally efficient, exact, covariate-adjusted genetic principal component analysis by leveraging individual marker summary statistics from large biobanks.

The popularization of biobanks provides an unprecedented amount of genetic and phenotypic information that can be used to research the relationship between genetics and human health. Despite the opportunities these datasets provide, they also pose many problems associated with computational time and costs, data size and transfer, and privacy and security. The publishing of summary statistics from these biobanks, and the use of them in a variety of downstream statistical analyses, alleviates many of these logistical problems. However, major questions remain about how to use summary statistics in all but the simplest downstream applications. Here, we present a novel approach to utilize basic summary statistics (estimates from single marker regressions on single phenotypes) to evaluate more complex phenotypes using multivariate methods. In particular, we present a covariate-adjusted method for conducting principal component analysis (PCA) utilizing only biobank summary statistics. We validate exact formulas for this method, as well as provide a framework of estimation when specific summary statistics are not available, through simulation. We apply our method to a real data set of fatty acid and genomic data.

Strategies to improve control of sexually transmissible infections in remote Australian Aboriginal communities: a stepped-wedge, cluster-randomised trial.

BACKGROUND: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. METHODS: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16-34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12610000358044. FINDINGS: Between April, 2010, and April, 2011, we recruited 68 primary care centres and grouped them into 24 clusters, which were randomly assigned into year 1 clusters (estimated population aged 16-34 years, n=11 286), year 2 clusters (n=10 288), or year 3 clusters (n=13 304). One primary health-care centre withdrew from the study due to restricted capacity to participate. We detected no difference in the relative prevalence of STIs between intervention and control clusters (adjusted relative risk [RR] 0·97, 95% CI 0·84-1·12; p=0·66). However, testing coverage was substantially higher in intervention clusters (22%) than in control clusters (16%; RR 1·38; 95% CI 1·15-1·65; p=0·0006). INTERPRETATION: Our intervention increased STI testing coverage but did not have an effect on prevalence. Additional interventions that will provide increased access to both testing and treatment are required to reduce persistently high prevalences of STIs in remote communities. FUNDING: Australian National Health and Medical Research Council.

Qualitative perspectives on the sustainability of sexual health continuous quality improvement in clinics serving remote Aboriginal communities in Australia.

OBJECTIVES: To examine barriers and facilitators to sustaining a sexual health continuous quality improvement (CQI) programme in clinics serving remote Aboriginal communities in Australia. DESIGN: Qualitative study. SETTING: Primary health care services serving remote Aboriginal communities in the Northern Territory, Australia. PARTICIPANTS: Seven of the 11 regional sexual health coordinators responsible for supporting the Northern Territory Government Remote Sexual Health Program. METHODS: Semi-structured in-depth interviews conducted in person or by telephone; data were analysed using an inductive and deductive thematic approach. RESULTS: Despite uniform availability of CQI tools and activities, sexual health CQI implementation varied across the Northern Territory. Participant narratives identified five factors enhancing the uptake and sustainability of sexual health CQI. At clinic level, these included adaptation of existing CQI tools for use in specific clinic contexts and risk environments (eg, a syphilis outbreak), local ownership of CQI processes and management support for CQI. At a regional level, factors included the positive framing of CQI as a tool to identify and act on areas for improvement, and regional facilitation of clinic level CQI activities. Three barriers were identified, including the significant workload associated with acute and chronic care in Aboriginal primary care services, high staff turnover and lack of Aboriginal staff. Considerations affecting the future sustainability of sexual health CQI included the need to reduce the burden on clinics from multiple CQI programmes, the contribution of regional sexual health coordinators and support structures, and access to and use of high-quality information systems. CONCLUSIONS: This study contributes to the growing evidence on how CQI approaches may improve sexual health in remote Australian Aboriginal communities. Enhancing sustainability of sexual health CQI in this context will require ongoing regional facilitation, efforts to build local ownership of CQI processes and management of competing demands on health service staff.

High Adherence to HIV Pre-exposure Prophylaxis and No HIV Seroconversions Despite High Levels of Risk Behaviour and STIs: The Australian Demonstration Study PrELUDE.

PrELUDE study evaluated daily pre-exposure prophylaxis (PrEP) in high-risk individuals in Australia. This open-label, single-arm study tested participants for HIV/STI and collected behavioural information three-monthly. We report trends over 18 months in medication adherence, side-effects, HIV/STI incidence and behaviour. 320 gay/bisexual men (GBM), 4 women and 3 transgender participants, followed on average 461 days, reported taking seven pills/week on 1,591 (88.5%) occasions and 4-6 pills/week on 153 (8.5%) occasions. No HIV infections were observed. STI incidence was high and stable, while gonorrhoea infections declined from 100.0 to 25.8/100 person-years between 6 and 15 months (p < 0.001). The number of HIV-positive and unknown-status sex partners, and condomless anal intercourse, significantly increased. In this high-risk cohort of mainly GBM, increases in risk behaviours and high STI incidence were not accompanied by HIV infections due to high adherence to daily PrEP. The study informed policy and further PrEP implementation among Australian GBM.

Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project.

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15-1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555.

Evaluating the performance of gene-based tests of genetic association when testing for association between methylation and change in triglyceride levels at GAW20.

Although methylation data continues to rise in popularity, much is still unknown about how to best analyze methylation data in genome-wide analysis contexts. Given continuing interest in gene-based tests for next-generation sequencing data, we evaluated the performance of novel gene-based test statistics on simulated data from GAW20. Our analysis suggests that most of the gene-based tests are detecting real signals and maintaining the Type I error rate. The minimum p value and threshold-based tests performed well compared to single-marker tests in many cases, especially when the number of variants was relatively large with few true causal variants in the set.

Epigenome wide association study of SNP-CpG interactions on changes in triglyceride levels after pharmaceutical intervention: a GAW20 analysis.

In the search for an understanding of how genetic variation contributes to the heritability of common human disease, the potential role of epigenetic factors, such as methylation, is being explored with increasing frequency. Although standard analyses test for associations between methylation levels at individual cytosine-phosphate-guanine (CpG) sites and phenotypes of interest, some investigators have begun testing for methylation and how methylation may modulate the effects of genetic polymorphisms on phenotypes. In our analysis, we used both a genome-wide and candidate gene approach to investigate potential single-nucleotide polymorphism (SNP)-CpG interactions on changes in triglyceride levels. Although we were able to identify numerous loci of interest when using an exploratory significance threshold, we did not identify any significant interactions using a strict genome-wide significance threshold. We were also able to identify numerous loci using the candidate gene approach, in which we focused on 18 genes with prior evidence of association of triglyceride levels. In particular, we identified GALNT2 loci as containing potential CpG sites that moderate the impact of genetic polymorphisms on triglyceride levels. Further work is needed to provide clear guidance on analytic strategies for testing SNP-CpG interactions, although leveraging prior biological understanding may be needed to improve statistical power in data sets with smaller sample sizes.

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.

An audit on the management and outcomes of infants at risk of congenital syphilis in the Top End of the Northern Territory, Australia, 2005-2013.

INTRODUCTION: Congenital syphilis (CS) remains a condition of serious clinical and public health importance, particularly in the Aboriginal populations of northern Australia, which have seen a recent resurgence in cases. In 2005, the Northern Territory (NT) Centre for Disease Control (CDC) published guidelines for management of infants at risk of CS. We audited the management and outcomes of infants at risk of CS who were born between 2005 and 2013 in the Darwin and Katherine regions of the NT. METHODS: Data, including serology, clinical examination, treatment, follow-up and infant outcomes at 12 months, were extracted from the Syphilis Register, medical and pathology records to assess clinician compliance with the CDC guidelines. RESULTS: Thirty-three infants were identified as being at risk of CS, 26 low risk and 7 high risk. Hospital management at birth conformed well with the guidelines, with 85% of low risk, and 100% of high risk infants receiving treatment and 92% of low risk and 86% of high risk having appropriate serology. Follow-up was poorly compliant, with only 48% of infants completing serological follow-up and less than 15% undergoing clinical examination. No definitive case of CS was identified among the at-risk children. CONCLUSIONS: Overall, peri-natal management of infants was performed well, but follow-up was poor. Effective systems to transfer care from hospitals to primary care are required to improve this. The fact that no infant had direct evidence of syphilis infection suggests consideration should be given to modifying the Australian surveillance case definition.