Potentiating antibody-dependent killing of cancers with CAR T cells secreting CD47-SIRPα checkpoint blocker.

Chimeric antigen receptor (CAR) T-cell therapy has shown success in the treatment of hematopoietic malignancies; however, relapse remains a significant issue. To overcome this, we engineered "Orexi" CAR T cells to locally secrete a high-affinity CD47 blocker, CV1, at the tumor and treated tumors in combination with an orthogonally targeted monoclonal antibody. Traditional CAR T cells plus the antibody had an additive effect in xenograft models, and this effect was potentiated by CAR T-cell local CV1 secretion. Furthermore, OrexiCAR-secreted CV1 reversed the immunosuppression of myelomonocytoid cells both in vitro and within the tumor microenvironment. Local secretion of the CD47 inhibitor bypasses the CD47 sink found on all cells in the body and may prevent systemic toxicities. This combination of CAR T-cell therapy, local CD47 blockade, and orthogonal antibody may be a combinatorial strategy to overcome the limitations of each monotherapy.

A TCR mimic CAR T cell specific for NDC80 is broadly reactive with solid tumors and hematologic malignancies.

Target identification for chimeric antigen receptor (CAR) T-cell therapies remains challenging due to the limited repertoire of tumor-specific surface proteins. Intracellular proteins presented in the context of cell surface HLA provide a wide pool of potential antigens targetable through T-cell receptor mimic antibodies. Mass spectrometry (MS) of HLA ligands from 8 hematologic and nonhematologic cancer cell lines identified a shared, non-immunogenic, HLA-A*02-restricted ligand (ALNEQIARL) derived from the kinetochore-associated NDC80 gene. CAR T cells directed against the ALNEQIARL:HLA-A*02 complex exhibited high sensitivity and specificity for recognition and killing of multiple cancer types, especially those of hematologic origin, and were efficacious in mouse models against a human leukemia and a solid tumor. In contrast, no toxicities toward resting or activated healthy leukocytes as well as hematopoietic stem cells were observed. This shows how MS can inform the design of broadly reactive therapeutic T-cell receptor mimic CAR T-cell therapies that can target multiple cancer types currently not druggable by small molecules, conventional CAR T cells, T cells, or antibodies.

Engineering CAR-T cells to activate small-molecule drugs in situ.

Chimeric antigen receptor (CAR)-T cells represent a major breakthrough in cancer therapy, wherein a patient's own T cells are engineered to recognize a tumor antigen, resulting in activation of a local cytotoxic immune response. However, CAR-T cell therapies are currently limited to the treatment of B cell cancers and their effectiveness is hindered by resistance from antigen-negative tumor cells, immunosuppression in the tumor microenvironment, eventual exhaustion of T cell immunologic functions and frequent severe toxicities. To overcome these problems, we have developed a novel class of CAR-T cells engineered to express an enzyme that activates a systemically administered small-molecule prodrug in situ at a tumor site. We show that these synthetic enzyme-armed killer (SEAKER) cells exhibit enhanced anticancer activity with small-molecule prodrugs, both in vitro and in vivo in mouse tumor models. This modular platform enables combined targeting of cellular and small-molecule therapies to treat cancers and potentially a variety of other diseases.

Regulators of the secretory pathway have distinct inputs into single-celled branching morphogenesis and seamless tube formation in the Drosophila trachea.

Biological tubes serve as conduits through which gas, nutrients and other important fluids are delivered to tissues. Most biological tubes consist of multiple cells connected by epithelial junctions. Unlike these multicellular tubes, seamless tubes are unicellular and lack junctions. Seamless tubes are present in various organ systems, including the vertebrate vasculature, C.elegans excretory system, and Drosophila tracheal system. The Drosophila tracheal system is a network of air-filled tubes that delivers oxygen to all tissues. Specialized cells within the tracheal system, called terminal cells, branch extensively and form seamless tubes. Terminal tracheal tubes are polarized; the lumenal membrane has apical identity whereas the outer membrane exhibits basal characteristics. Although various aspects of membrane trafficking have been implicated in terminal cell morphogenesis, the precise secretory pathway requirements for basal and apical membrane growth have yet to be elucidated. In the present study, we demonstrate that anterograde trafficking, retrograde trafficking and Golgi-to-plasma membrane vesicle fusion are each required for the complex branched architecture of the terminal cell, but their inputs during seamless lumen formation are more varied. The COPII subunit, Sec31, and ER exit site protein, Sec16, are critical for subcellular tube architecture, whereas the SNARE proteins Syntaxin 5, Syntaxin 1 and Syntaxin 18 are more generally required for seamless tube growth and maintenance. These data suggest that distinct components of the secretory pathway have differential contributions to basal and apical membrane growth and maintenance during terminal cell morphogenesis.

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.

Web-Based STI/HIV Testing Services Available for Access in Australia: Systematic Search and Analysis.

BACKGROUND: Sexually transmitted infection (STI) rates continue to rise in Australia, and timely access to testing and treatment is crucial to reduce transmission. Web-based services have been viewed as a way to improve timely access to STI/HIV testing and have proliferated in recent years. However, the regulation of these services in Australia is minimal, leading to concerns about their quality. The purpose of this review was to systematically identify web-based STI/HIV testing services available in Australia and assess them on aspects of quality, reliability, and accessibility. OBJECTIVE: We aim to systematically identify and assess web-based STI/HIV testing services available in Australia. METHODS: A Google search of Australian web-based services was conducted in March 2022 and repeated in September 2022 using Boolean operators and search terms related to test services (eg, on the internet or home), STIs (eg, chlamydia or gonorrhea), and test type (eg, self-test). The first 10 pages were assessed, and services were categorized as self-testing (ST; test at home), self-sampling (SS; sample at home and return to laboratory), or self-navigated pathology (SNP; specimens collected at pathology center). Website reliability was assessed against the Health on the Net Foundation code of conduct, and service quality was assessed using a scorecard that was developed based on similar reviews, Australian guidelines for in-person services, and UK standards. Additionally, we looked at measures of accessibility including cost, rural access, and time to test results. RESULTS: Seventeen services were identified (8 ST, 2 SS, and 7 SNP). Only 4 services offered recommended testing for all 4 infections (chlamydia, gonorrhea, syphilis, and HIV) including genital, anorectal, and oropharyngeal sites, and 5 offered tests other than those recommended by Australian testing guidelines (eg, Ureaplasma). Nine services (1 SNP, 8 self-test) had no minimum age requirements for access. Reliability scores (scale 0-8) were similar between all services (range 4.75-8.0). Quality weighted scores (scale 0-58) were similar between SNP and SS services (average 44.89, SD 5.56 and 44.75, SD 1.77, respectively) but lower for ST services (22.66, SD 8.93; P=.002). Government-funded services were of higher quality than private services (43.54, SD 6.71 vs 29.43, SD 13.55; P=.03). The cost for services varied between SNP (Aus $0-$595; ie, US $0-$381.96), self-sample (Aus $0; ie, US $0), and ST (Aus $0-$135; ie, US $0-$86.66). The time to test results was much shorter for SNP services (~4 days) than for SS (~12 days) and ST (~14 days). CONCLUSIONS: This review identified considerable variability in the quality and reliability of the web-based STI/HIV testing services in Australia. Given the proliferation and use of these services will likely increase, it is imperative that Australia develops national standards to ensure the standard-of-care offered by web-based STI/HIV testing services is appropriate to protect Australian users from the impact of poorly performing and inappropriate tests.

Integrating testing for sexually transmissible infections into annual health assessments for Aboriginal and Torres Strait Islander young people: a cross-sectional analysis.

BACKGROUND: In the context of an expanding syphilis epidemic, we assessed the integration of sexually transmissible infection (STI) testing within annual health assessments for Aboriginal and Torres Strait Islander young people aged 16-29years in Aboriginal Community Controlled Health Services between 2018 and 2020. METHODS: Using routinely collected electronic medical record data from a national sentinel surveillance system (ATLAS), we performed a cross-sectional analysis to calculate the proportion of assessments that integrated any or all of the tests for chlamydia, gonorrhoea, syphilis, and HIV. We used logistic regression to identify correlates of integration of any STI test. RESULTS: Of the 13 892 assessments, 23.8% (95% CI 23.1, 24.6) integrated a test for any STI and 11.5% (95% CI 10.9, 12.0) included all four STIs. Of assessments that included a chlamydia/gonorrhoea test, 66.9% concurrently included a syphilis test. Integration of any STI test was associated with patients aged 20-24years (OR 1.2, 95% CI 1.1-1.4) and 25-29years (OR 1.1, 95% CI 1.0-1.2) compared to 16-19years and patients residing in very remote (OR 4.2, 95% CI 3.7-4.8), remote (OR 2.4, 95% CI 2.1-2.8), and regional areas (OR 2.5, 95% CI 2.2-2.8) compared to metropolitan areas. There was no association with patient sex. CONCLUSIONS: Integration of STI testing into annual health assessments for Aboriginal and Torres Strait Islander young people was higher in remote areas where disease burden is greatest. Integration is similar in men and women, which contrasts with most studies that have found higher testing in women.

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.

Patient delivered partner therapy for chlamydia infection is used by some general practitioners, but more support is needed to increase uptake: findings from a mixed-methods study.

OBJECTIVES: Patient-delivered partner therapy (PDPT) describes the giving of a prescription or antibiotics by an index case with chlamydia to their sexual partners. PDPT has been associated with higher numbers of partners receiving treatment. In Australia, general practitioners (GPs) previously expressed negative views about PDPT. Health authority guidance for PDPT has since been provided in some areas. We investigated recent use and perceptions of PDPT for chlamydia among GPs in Australia. METHODS: In 2019, we conducted an online survey comprising multiple-choice and open-ended questions to investigate GPs' chlamydia management practices, including PDPT. Logistic regression identified factors associated with ever offering PDPT. A directed content analysis of free-text data explored GPs' perceptions towards PDPT. RESULTS: The survey received responses from 323 GPs; 85.8% (n=277) answered PDPT-focused questions, providing 628 free-text comments. Over half (53.4%) reported never offering PDPT, while 36.5% sometimes and 10.1% often offered PDPT. GPs more likely to offer PDPT were aged ≥55 years (adjusted OR (AOR) 2.9, 95% CI 1.4 to 5.8), worked in non-metropolitan areas (AOR 2.5, 95% CI 1.5 to 4.4) and jurisdictions with health authority PDPT guidance (AOR 2.3, 95% CI 1.4 to 3.9). Qualitative data demonstrated that many GPs recognised PDPT's potential to treat harder to engage partners but expressed hesitancy to offer PDPT because they considered partners attending for care as best practice. GPs emphasised a case-by-case approach that considered patient and partner circumstances to determine PDPT suitability. To alleviate medicolegal concerns, many GPs indicated a need for professional and health authority guidance that PDPT is permissible. They also desired practical resources to support its use. CONCLUSION: GPs appear to accept the place of PDPT as targeted to those who may otherwise not access testing or treatment. Availability of health authority guidance appears to have supported some GPs to incorporate PDPT into their practice.

Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection.

Cellular therapies are engineered using foreign and synthetic protein sequences, such as chimeric antigen receptors (CARs). The frequently observed humoral responses to CAR T cells result in rapid clearance, especially after re-infusions. There is an unmet need to protect engineered cells from host-versus-graft rejection, particularly for the advancement of allogeneic cell therapies. Here, utilizing the immunoglobulin G (IgG) protease "IdeS," we programmed CAR T cells to defeat humoral immune attacks. IdeS cleavage of host IgG averted Fc-dependent phagocytosis and lysis, and the residual F(ab')2 fragments remained on the surface, providing cells with an inert shield from additional IgG deposition. "Shield" CAR T cells efficiently cleaved cytotoxic IgG, including anti-CAR antibodies, detected in patient samples and provided effective anti-tumor activity in the presence of anti-cell IgG in vivo. This technology may be useful for repeated human infusions of engineered cells, more complex engineered cells, and expanding widespread use of "off-the-shelf" allogeneic cellular therapies.

Sustaining sexual and reproductive health through COVID-19 pandemic restrictions: qualitative interviews with Australian clinicians.

BACKGROUND: The sexual and reproductive health care of people with HIV and those at risk of HIV has largely been delivered face-to-face in Australia. These services adapted to the coronavirus disease 2019 (COVID-19) pandemic with a commitment to continued care despite major impacts on existing models and processes. Limited attention has been paid to understanding the perspectives of the sexual and reproductive health care workforce in the research on COVID-19 adaptations. METHODS: Semi-structured interviews were conducted between June and September 2021 with 15 key informants representing a diverse range of service settings and professional roles in the Australian sexual and reproductive health sector. Inductive themes were generated through a process of reflexive thematic analysis, informed by our deductive interest in clinical adaptations. RESULTS: The major adaptations were: triage (rapidly adapting service models to protect the most essential forms of care); teamwork (working together to overcome ongoing threats to service quality and staff wellbeing), and the intwined themes of telehealth and trust (remaining connected to marginalised communities through remote care). Despite impacts on care models and client relationships, there were sustained benefits from the scaleup of remote care, and attention to service safety, teamwork and communication. CONCLUSIONS: Attending to the experiences of those who worked at the frontline of the COVID-19 response provides essential insights to inform sustained, meaningful system reform over time. The coming years will provide important evidence of longer-term impacts of COVID-19 interruptions on both the users and providers of sexual and reproductive health services.

The need for sexual health clinics, their future role, and contribution to public health.

Specialised sexual health clinics (SHCs) play an important role in addressing the staggering rates of STIs seen in many high-income nations. Despite increasing healthcare coverage in the US and nationalised health care in some countries, there is a continued need for SHCs to meet the needs of patients and the community, especially for high-priority populations: those at high risk of STI acquisition and/or groups historically marginalised and underserved in the traditional healthcare system. We need to mobilise resources to support a stronger clinical infrastructure in specialised SHCs. This review describes the importance of SHCs, their future role, and some of the innovative programs housed within SHCs in the US, Australia, and the Netherlands to address both STI and HIV prevention for the populations they serve.

Syphilis, HIV and other STI positivity in clients presenting as contacts of syphilis at Sydney Sexual Health Centre.

There is a paucity of contemporary data pertaining to sexually transmitted infection test positivity of people presenting as contacts of syphilis. Over a 12 month period in 2018, within a sexual health service, we identified 191 (92% men who have sex with men) presentations, 7.8% were diagnosed with syphilis (three primary, four secondary, six early latent and two late latent infections). A total of 20.8% (38/183) were diagnosed with one or more STI including 54 non-syphilis infections: two (1.1%) new HIV; 26 (14.2%) Chlamydia trachomatis; and 24 (13.1%) Neisseria gonorrhoeae. Although syphilis test positivity in contacts is low, this population requires comprehensive STI screening and HIV prevention discussion.

STI testing among young people attending music festivals in New South Wales, Australia: exploring the client segmentation concept in the 'Down to Test' program.

Background The 'Down to Test (DTT)' campaign is a sexually transmissible infection (STI) social marketing intervention delivered through outdoor music festival activations and supported by digital media communications in New South Wales, Australia. This paper investigates whether and how the tailored messages reached the intended audience. Methods Data was collected through three annual rounds of online surveys post campaign exposure, targeting young people (aged 15-29years) attending 14 music festivals in NSW from October 2017 to March 2020. Descriptive statistics, principal component analysis and multivariable logic regression were applied to identify the key client segment and factors associated with a strong intention for future STI screening. Results Of the 10044 participants with a valid urine specimen submitted, 261 (2.8%) tested positive for chlamydia. Altogether, 1776 participants (median age=22) self-completed the evaluation surveys online with more being female (73.4%) than male (26.2%). Participants were mostly Australian-born (89.5%), heterosexual (82.6%) and the majority being sexually active (96.7%). Rates of self-reported lifetime STI testing (70.4%) and intention for future STI screening ('definitely yes' in the next 12months, 39.0%) were also high. The most significant factor associated with future intention for STI testing is the Sexual Experience and Perception Factor (adjusted odds ratio [AOR]=2.02; 95%CI 1.76-2.32; P<0.001), followed by the Sexual Beliefs and Attitudes Factor (AOR=1.14; 95% CI 1.01-1.30; P<0.05). Conclusions The NSW state-wide DTT campaign has largely reached sexually active youth who are attentive to sexual health promotion messages and contributed to enhanced STI screening in a fun and peer-supportive environment.

Neisseria gonorrhoeae positivity in clients presenting as asymptomatic contacts of gonorrhoea at a sexual health centre.

Background Previous guidelines at the Sydney Sexual Health Centre (SSHC) recommended empirical antibiotic treatment for asymptomatic contacts of Neisseria gonorrhoeae at the time of testing. With increasing concerns around gonorrhoea antibiotic resistance, it has been suggested that asymptomatic contacts should only be treated based on test results. METHODS: This retrospective study of data from the SSHC electronic medical record included a total of 295 gonorrhoea contacts from 1 January 2018 to 30 June 2018. The primary outcome was the proportion of asymptomatic gonorrhoea contacts with a positive gonorrhoea result from any anatomical site. Statistically significant differences in gonorrhoea positivity according to gender, sexual preference, use of PrEP, sex worker status, country of birth, preferred language and number of partners, were calculated using Fisher's exact test. RESULTS: The overall proportion of asymptomatic gonorrhoea contacts with a positive gonorrhoea result was 27.1% (95% CI: 22.1-32.6%). The proportion of gonorrhoea positivity was significantly higher in females compared to males (52.0% vs 25.7%, P < 0.01), gay and bisexual men compared to heterosexual men (28.7% vs 0%, P < 0.01) and non-users of PrEP compared to PrEP users (31.2% vs 12.5%, P < 0.05). No statistically significant differences in gonorrhoea positivity were found in subgroups divided by sex worker status, country of birth, preferred language and number of partners. CONCLUSION: The relatively low gonorrhoea positivity rate (27.1%) in asymptomatic gonorrhoea contacts at the SSHC between January and June 2018 supports guideline changes to no longer provide empirical antibiotic treatment to asymptomatic contacts.

Patient-delivered partner therapy for chlamydia in Australia: can it become part of routine care?

Background Patient-delivered partner therapy (PDPT) is a method for an index patient to give treatment for genital chlamydia to their sexual partner(s) directly. In Australia, PDPT is considered suitable for heterosexual partners of men and women, but is not uniformly endorsed. We explored the policy environment for PDPT in Australia and considered how PDPT might become a routine option. METHODS: Structured interviews were conducted with 10 key informants (KIs) representing six of eight Australian jurisdictions and documents relevant to PDPT were appraised. Interview transcripts and documents were analysed together, drawing on KIs' understanding of their jurisdiction to explore our research topics, namely the current context for PDPT, challenges, and actions needed for PDPT to become routine. RESULTS: PDPT was allowable in three jurisdictions (Victoria, New South Wales, Northern Territory) where State governments have formally supported PDPT. In three jurisdictions (Western Australia, Australian Capital Territory, Tasmania), KIs viewed PDPT as potentially allowable under relevant prescribing regulations; however, no guidance was available. Concern about antimicrobial stewardship precluded PDPT inclusion in the South Australian strategy. For Queensland, KIs viewed PDPT as not allowable under current prescribing regulations and, although a Medicine and Poisons Act was passed in 2019, it is unclear if PDPT will be possible under new regulations. Clarifying the doctor-partner treating relationship and clinical guidance within a care standard were viewed as crucial for PDPT uptake, irrespective of regulatory contexts. CONCLUSION: Endorsement and guidance are essential so doctors can confidently and routinely offer PDPT in respect to professional standards and regulatory requirements.

Sexually transmissible infections among transgender men and women attending Australian sexual health clinics.

OBJECTIVES: To estimate rates of HIV infection, chlamydia, gonorrhoea, and infectious syphilis in transgender men and women in Australia; to compare these rates with those for cisgender people. DESIGN: Cross-sectional, comparative analysis of de-identified health data. SETTING, PARTICIPANTS: We analysed data for 1260 transgender people (404 men, 492 women, 364 unrecorded gender), 78 108 cisgender gay and bisexual men, and 309 740 cisgender heterosexual people who attended 46 sexual health clinics across Australia during 2010-2017. MAIN OUTCOME MEASURES: First-visit test positivity for sexually transmitted infections (STIs), stratified by patient group and year; demographic and behavioural factors associated with having STIs. RESULTS: 14 of 233 transgender men (6.0%) and 34 of 326 transgender women (10%) tested during first clinic visits were chlamydia-positive; nine transgender men (4%) and 28 transgender women (8.6%) were gonorrhoea-positive. One of 210 tested transgender men (0.5%) and ten of 324 tested transgender women (3.1%) were diagnosed with infectious syphilis; 14 transgender men (3.5%) and 28 transgender women (5.7%) were HIV-positive at their first visit. The only significant change in prevalence of an STI among transgender patients during the study period was the increased rate of gonorrhoea among transgender women (from 3.1% to 9.8%). Compared with cisgender gay and bisexual men, transgender men were less likely (adjusted odds ratio [aOR], 0.46; 95% CI, 0.29-0.71; P = 0.001) and transgender women as likely (aOR, 0.98; 95% CI, 0.73-1.32; P = 0.92) to be diagnosed with a bacterial STI; compared with heterosexual patients, transgender men were as likely (aOR, 0.72; 95% CI, 0.46-1.13; P = 0.16) and transgender women more likely (aOR, 1.56; 95% CI, 1.16-2.10; P = 0.003) to receive a first-visit bacterial STI diagnosis. CONCLUSIONS: The epidemiology of STIs in transgender people attending Australian sexual health clinics differs from that of cisgender patients. Gender details must be captured by health data systems to facilitate appropriate delivery of sexual health care.

Missed opportunities for HIV pre-exposure prophylaxis during a rapid scale-up program at Sydney Sexual Health Centre.

We aimed to estimate HIV pre-exposure prophylaxis (PrEP) uptake and missed opportunities for PrEP through a retrospective review of medical records of clients at high risk of HIV attending the Sydney Sexual Health Centre. Most clients (69%) were taking PrEP, and 7% of those eligible for PrEP were classified as a missed opportunity for PrEP. Although missed opportunities were uncommon, PrEP discussions should be a standard component of care for all clients at risk of HIV acquisition.

ADOPTing a new method of partner management for genital chlamydia in New South Wales: findings from a pilot implementation program of patient-delivered partner therapy.

Background Patient-delivered partner therapy (PDPT) for chlamydia is an effective and safe additional partner management strategy. Some Australian regulatory changes have been made to support PDPT, but implementation guidance is lacking. This paper describes a pilot implementation program of PDPT in New South Wales (NSW), the Australian Development and Operationalisation of Partner Therapy (ADOPT). METHODS: ADOPT involved: (1) clarification of the NSW PDPT legal and policy framework; (2) development and implementation of PDPT service models, resources and data collection tools for select publicly funded sexual health services (PFSHS) and Family Planning (FP) NSW clinics; and (3) evaluation of PDPT uptake. RESULTS: PDPT can be undertaken in NSW if accompanied by adequate provider, patient and partner information. Regulatory amendments enabled medication prescribing. The pilot implementation took place in four PFSHS and five FPNSW clinics from January to December 2016. In PFSHS, 30% of eligible patients were offered PDPT and 89% accepted the offer. In FPNSW clinics, 42% of eligible patients were offered PDPT and 63% accepted the offer. Most partners for whom PDPT was accepted were regular partners. CONCLUSIONS: A close collaboration of researchers, policy makers and clinicians allowed successful implementation of a PDPT model for chlamydia in heterosexual patients at select PFSHS and FPNSW clinics, providing guidance on its use as standard of care. However, for the full public health benefits of PDPT to be realised, it must be implemented in general practice, where most chlamydia is diagnosed. Further work is recommended to explore feasibility, develop guidelines and promote the integration of PDPT into general practice.

Gonorrhoea gone wild: rising incidence of gonorrhoea and associated risk factors among gay and bisexual men attending Australian sexual health clinics.

Background Gonorrhoea notifications continue to rise among gay and bisexual men in Australia and around the world. More information is needed on infection trends, accounting for testing and complimented by demographics and risk practices. METHODS: A retrospective cohort analysis was undertaken using repeat gonorrhoea testing data among gay and bisexual men from 2010 to 2017, which was extracted from a network of 47 sexual health clinics across Australia. Poisson and Cox regression analyses were used to determine temporal trends in gonorrhoea incidence rates, as well as associated demographic and behavioural factors. RESULTS: The present analysis included 46904 gay and bisexual men. Gonorrhoea incidence at any anatomical site increased from 14.1/100 person years (PY) in 2010 to 24.6/100 PY in 2017 (P<0.001), with the greatest increase in infections of the pharynx (5.6-15.9/100 PY, P<0.001) and rectum (6.6-14.8/100 PY, P<0.001). After adjusting for symptomatic and contact-driven presentations, the strongest predictors of infection were having more than 20 sexual partners in a year (hazard ratio (HR)=1.9, 95% confidence interval (CI): 1.7-2.2), using injecting drugs (HR=1.7, 95%CI: 1.4-2.0), being HIV positive (HR=1.4, 95%CI: 1.2-1.6) and being aged less than 30 years old (HR=1.4, 95%CI: 1.2-1.6). CONCLUSIONS: Gonorrhoea has increased dramatically among gay and bisexual men in Australia. Enhanced prevention efforts, as well as more detailed, network-driven research are required to combat gonorrhoea among young men, those with HIV and those who use injecting drugs.