Australian consensus statement on doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual and other men who have sex with men.

INTRODUCTION: Doxycycline post-exposure prophylaxis (doxy-PEP) involves consuming 200 mg of doxycycline up to 72 hours after a condomless sex act to reduce the risk of bacterial sexually transmitted infections (STIs). Recent clinical trials of doxy-PEP have demonstrated significant reductions in syphilis, chlamydia and, to a lesser degree, gonorrhoea among gay, bisexual and other men who have sex with men (GBMSM). There is a high level of interest in doxy-PEP in the GBMSM community and, in response, the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) held a national consensus conference with the aim of creating preliminary guidance for clinicians, community, researchers and policy makers. MAIN RECOMMENDATIONS: There was broad agreement that doxy-PEP should be considered primarily for the prevention of syphilis in GBMSM who are at risk of this STI, with a secondary benefit of reductions in other bacterial STIs. At the end of the consensus process, there remained some disagreement, as some stakeholders felt strongly that doxy-PEP should be considered only for the prevention of syphilis in GBMSM, and that the risk of increasing antimicrobial resistance outweighed any potential benefit from reductions in other bacterial STIs in the target population. The national roundtable made several other recommendations for clinicians, community, researchers and policy makers, as detailed in this article. ASHM will support the development of detailed clinical guidelines and education materials on doxy-PEP (www.ashm.org.au/doxy-pep). CHANGES IN MANAGEMENT AS A RESULT OF THIS CONSENSUS STATEMENT: For GBMSM at high risk of syphilis, and perhaps other bacterial STIs, clinicians may consider prescribing doxy-PEP for a limited period of time, followed by a review of ongoing need. Unlike human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP), doxy-PEP may not be suitable as a population-level intervention and should instead be used more selectively.

National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018-2020: Uptake After Commercial Availability of HIV Self-Tests.

HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.

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.

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.

Why sexual health clinics are important in the 2020s.

To make services more accessible, acceptable and affordable, sexual health service delivery models have embraced innovation, technology, outreach and decentralisation. In particular, some routine high-volume services, like asymptomatic testing for sexually transmitted infections (STIs), can be delivered in general practice, online or in non-clinical settings. On the surface, sexual health clinics, like hospitals or other primary care clinics, might appear to be operating on a model that has not changed significantly in recent times. However, globally sexual healthcare needs are rising both in volume and complexity, not all of which can be adequately met through decentralised care. Sexual health clinics themselves are the site of considerable innovation. The importance of sexual health clinics in the diagnosis and treatment of symptomatic STIs is likely to increase with the increasing burden of disease, the complexity of treatment guidelines and the emergence of new infections. Services essential to patient health such as immediate or complex clinical care, partner notification and safeguarding, and activities essential to the health system like research, training and supervision require expertise to be located where it can be accessed and maintained at reasonable cost. We do not know whether increasing some services outside existing models can safely compensate for reducing other services inside them.

Surveillance systems to monitor antimicrobial resistance in Neisseria gonorrhoeae: a global, systematic review, 1 January 2012 to 27 September 2020.

BackgroundEffective surveillance of antimicrobial resistance (AMR) in Neisseria gonorrhoeae is required for the early detection of resistant strains and to ensure that treatment guidelines are appropriate for the setting in which they are implemented. AMR in N. gonorrhoeae has been identified as a global health threat.AimWe performed a systematic review to identify and describe surveillance systems targeting AMR in N. gonorrhoeae.MethodsWe searched Medline, PubMed, Global Health, EMBASE, CINAHL, Web of Science and ProQuest databases and grey literature between 1 January 2012 and 27 September 2020. Surveillance systems were defined as the continuous, systematic collection, analysis and interpretation of N. gonorrhoeae resistance data. The key components of surveillance systems were extracted, categorised, described and summarised.ResultsWe found 40 publications reporting on N. gonorrhoeae AMR surveillance systems in 27 countries and 10 multi-country or global surveillance reports. The proportion of countries with surveillance systems in each of the WHO's six regions ranged from one of 22 countries in the Eastern Mediterranean and five of 54 in Africa, to three of 11 countries in South East Asia. Only four countries report systems which are both comprehensive and national. We found no evidence of a current surveillance system in at least 148 countries. Coverage, representativeness, volume, clinical specimen source, type and epidemiological information vary substantially and limit interpretability and comparability of surveillance data for public health action.ConclusionGlobally, surveillance for N. gonorrhoeae AMR is inadequate and leaves large populations vulnerable to a major public health threat.

Predicting the diagnosis of HIV and sexually transmitted infections among men who have sex with men using machine learning approaches.

OBJECTIVES: We aimed to develop machine learning models and evaluate their performance in predicting HIV and sexually transmitted infections (STIs) diagnosis based on a cohort of Australian men who have sex with men (MSM). METHODS: We collected clinical records of 21,273 Australian MSM during 2011-2017. We compared accuracies for predicting HIV and STIs (syphilis, gonorrhoea, chlamydia) diagnosis using four machine learning approaches against a multivariable logistic regression (MLR) model. RESULTS: Machine learning approaches consistently outperformed MLR. Gradient boosting machine (GBM) achieved the highest area under the receiver operator characteristic curve for HIV (76.3%) and STIs (syphilis, 85.8%; gonorrhoea, 75.5%; chlamydia, 68.0%), followed by extreme gradient boosting (71.1%, 82.2%, 70.3%, 66.4%), random forest (72.0%, 81.9%, 67.2%, 64.3%), deep learning (75.8%, 81.0%, 67.5%, 65.4%) and MLR (69.8%, 80.1%, 67.2%, 63.2%). GBM models demonstrated the ten greatest predictors collectively explained 62.7-73.6% of variations in predicting HIV/STIs. STIs symptoms, past syphilis infection, age, time living in Australia, frequency of condom use with casual male sexual partners during receptive anal sex and the number of casual male sexual partners in the past 12 months were most commonly identified predictors. CONCLUSIONS: Machine learning approaches are advantageous over multivariable logistic regression models in predicting HIV/STIs diagnosis.

The Impact of Markers of HIV Infection on Change in Liver Stiffness in People With HIV and Hepatitis C Virus Co-infection After Treatment and Cure of Hepatitis C.

BACKGROUND: Markers of HIV disease severity are associated with increased liver fibrosis in HIV/Hepatitis C virus (HCV) co-infected individuals. HCV treatment may reverse liver fibrosis, but evidence among HIV/HCV-co-infected populations and the impact of HIV parameters on fibrosis regression is limited. We aimed to assess the influence of surrogate markers of HIV-infection and other determinants of liver stiffness before HCV treatment and changes after HCV cure in people living with HIV. METHODS: We used data from an HCV treatment implementation study aiming for HCV micro-elimination among gay and bisexual men with HIV in Melbourne, Australia (co-EC Study). We obtained liver stiffness measurements (LSM) before and after direct-acting antiviral treatment using transient elastography (FibroScan). Linear mixed models were used to evaluate determinants of pretreatment LSM and changes in LSM following cure with duration in years between pre- and post-LSM assessment as main exposure variable. RESULTS: At least one LSM was available in 173 participants, and 98 participants had 2 LSMs. Median pre- and post-treatment LSMs were 5.7 and 5.1 kPa, respectively. Median time between transient elastography measurements was 1.3 years (interquartile range = 0.9-2.1). In multivariable analysis, longer duration of known HIV infection, a lower CD4 and CD8 T-cell count and hazardous alcohol consumption were associated with higher LSM values before treatment initiation. Successfully treated patients had a 6% (95% confidence interval = -10% to -2%) annual decrease (0.34 kPa predicted decrease) in LSM following cure. Changes in LSM values did not depend on any of the pretreatment HIV markers or other factors. CONCLUSION: Low levels of liver stiffness were observed before treatment initiation and a small decrease (6%) in LSM following HCV cure in people living with HIV. No clear predictors affecting change in LSM following cure were found in this study, including markers of HIV infection. However, markers of advanced HIV immunodeficiency and hazardous alcohol consumption remained associated with higher LSM values even after HCV cure.

Adherence to Antiretroviral Regimens in Australia: A Nationwide Cohort Study.

The lifetime use of combination antiretroviral therapy (cART) highlights the need to understand patterns of and factors associated with adherence to cART. In this cohort study using a 10% random sample of dispensing claims data for eligible Australians, we identified 2042 people dispensed cART between January 2016 and December 2017 (mean age 48.0 ± 12.0 years old, 88.6% male, and 85.9% treatment experienced). We considered people to be adherent if the proportion of treatment coverage days was ≥80% in the 360 days after their first observed cART dispensing. We also used group-based trajectory modeling (GBTM) to examine different patterns of adherence for 360 days from first observed cART dispensing. Most commonly, people receiving cART were treated with two nucleoside/nucleotide reverse transcriptase inhibitors with an integrase strand transfer inhibitors (INSTI-46.6%). Overall, 1708 people [83.6% (95% confidential interval 82.0-85.3%)] remained adherent over 360 days. GBTM identified three distinct adherence patterns: nearly always adherent [67.8% (63.7-71.9%) of the cohort], moderate adherence [26.6% (23.0-30.1%)], and low adherence [5.6% (4.1-7.2%)]. People were more likely to belong to the "nearly always adherent" trajectory if they were older (per additional year of age), treated with an INSTI regimen, and on treatment for more than 6 months. Our study demonstrates that the 360-day adherence to cART is generally high, but approximately one-third maintain a moderate or low adherence pattern. The use of INSTI regimens and additional support of treatment adherence, especially among younger people and those initiating therapy, may further improve adherence.

Estimates of the national trend of drugs use during 2000-2030 in China: A population-based mathematical model.

BACKGROUND: The use of synthetic drugs has exceeded heroin to become a major public health concern in China. We aimed to estimate the trend of heroin-only, synthetic drug-only and poly-drug (heroin and synthetic drug) use during 2000-2030 period in China using existing data. METHODS: We used data from the Annual Report on Drug Control in China and peer-reviewed publications. We constructed a mathematical model to estimate the drug use trend based on Monte Carlo simulations. RESULTS: The best calibrated model estimated that the number of drug users would increase from 0.86 million to 3,120,059 (95% CI 2,669,214-3,570,904) during 2000-2030 period. The proportion of heroin-only users among the total drug users will decrease from 96.8% (95% CI, 96.6-97.1%) in 2000 to 36.9% (30.1-40.8%) in 2030, while the proportion of synthetic drug-only users will increase from 1.1% (0.9-1.3%) in 2000 to 57.7% (51.7-65.6%) in 2030. In contrast, the proportion of poly-drug users shared an increasing trend during 2000-2016 (from 2.1% (1.5-2.8%) to 15.1 (13.8-17.1%)) but declined to 5.5% (3.4-7.2%) in 2030. Estimated 46,370 (41,634-51,106) heroin-only users and 3767 (3481-4053) synthetic drug only users initiated poly-drug use in 2000. We observed a cross-over in 2012 where more synthetic drug-only users were initiating heroin use than heroin-only users initiating synthetic drug use. There will be estimated 2,094,052 (1,819,830-2,368,274) synthetic drug-only users and poly-drug users 211,407 (177,150-245,664) in 2030. CONCLUSIONS: Synthetic drug use will become dominant in drug users in China, but poly-drug use of both heroin and synthetic drugs will remain substantial.

Incident HIV infection has fallen rapidly in men who have sex with men in Melbourne, Australia (2013-2017) but not in the newly-arrived Asian-born.

BACKGROUND: We examined differences in incident HIV infection between newly-arrived Asian-born and other men who have sex with men (MSM) after the introduction of universal HIV treatment guidelines in 2015 and pre-exposure prophylaxis in 2016. METHODS: Clinical, demographic, laboratory and behavioural data on MSM presenting for HIV testing at the Melbourne Sexual Health Centre from July 2013 to June 2017 were extracted. We compared the proportion of newly-arrived (four years or less in Australia), Asian-born and other MSM tested each year who were diagnosed with incident HIV infection (negative test within one year or diagnosis with indeterminate or negative Western Blot). RESULTS: We analysed 35,743 testing episodes in 12,180 MSM, including 2781 testing episodes in 1047 newly-arrived Asian-born MSM. The proportion of other MSM tested each year who were diagnosed with incident HIV infection fell from 0.83% in 2014 to 0.38% in 2017 (p = .001), but did not fall in newly-arrived Asian-born MSM (from 1.18% in 2014 to 1.56% in 2017, p = .76). In the multivariate logistic regression, in 2016/2017 but not in 2014/2015, being newly-arrived Asian-born was associated with an increased odds of diagnosis of incident HIV infection (aOR 3.29, 95%CI 1.82-5.94, p < .001). CONCLUSIONS: The epidemiology of HIV in Melbourne Australia has changed dramatically. While there has been an overall reduction amongst MSM, the incidence of HIV in newly-arrived Asian-born MSM remains high. Failing to address these new inequalities leaves individuals at risk and may offset the population benefit of biomedical HIV prevention.

Incidence of renal Fanconi syndrome in patients taking antiretroviral therapy including tenofovir disoproxil fumarate.

The objective of this study was to determine the incidence and predictors of Fanconi Syndrome (FS) in a cohort of patients taking tenofovir disoproxil fumarate (TDF). Clinical records and laboratory investigations from patients receiving TDF between 2002 and 2016 were extracted. FS was defined as normoglycaemic glycosuria and proteinuria and at least one other marker of renal dysfunction. Regression analysis was performed with time to development of FS and the following covariates: ritonavir co-administration, age, gender, co-morbidities (hypertension, hyperlipidaemia, diabetes, viral hepatitis), CD4 cell count nadir and baseline eGFR. One thousand and forty-four patients received TDF without ritonavir and 398 patients with ritonavir. Thirteen cases of FS were identified with a mean duration of exposure of 55 months. The incidence of FS was 1.09/1000PY (0.54-1.63) of TDF exposure (without ritonavir) and 5.50/1000PY (3.66-7.33) of TDF-ritonavir co-administration (p=0.0057). The adjusted hazards ratio for ritonavir co-administration was 4.71 (1.37-16.14, p=0.014). Known risk factors for chronic kidney disease were not associated with development of FS. Ritonavir co-administration, but not other factors, is associated with a greater risk of FS. FS developed late. Known risk factors for chronic kidney disease and length of treatment are not useful for identifying patients most at risk of developing FS in patients taking TDF.

Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016.

AIM: Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016. OBJECTIVES: We examined the time from HIV infection to virological suppression in MSM who were first diagnosed at Melbourne Sexual Health Centre between 2007 and 2016. DESIGN: Retrospective cohort. METHODS: Date of infection was imputed from the testing history or serological evidence of recent infection (negative or indeterminate western blot) or baseline CD4 cell count. Date of virological suppression was determined using clinical viral load data. We analysed predictors of diagnosis with serological evidence of recent infection (logistic regression) and time from diagnosis to suppression and from infection to suppression (Cox regression) using demographic, clinical, and behavioral covariates. RESULTS: Between 2007 and 2016, the median time from HIV infection to diagnosis fell from 6.8 to 4.3 months (P = 0.001), from diagnosis to suppression fell from 22.7 to 3.2 months (P < 0.0001), and from infection to suppression fell from 49.0 to 9.6 months (P < 0.0001). Serological evidence of recent infection increased from 15.6 to 34.3% (P < 0.0001) of diagnoses. In the multivariate analyses, age, being recently arrived from a non-English speaking country, history of IDU, other sexually transmitted infections, and sexual risk were not associated with any of these measures. CONCLUSION: The duration of infectiousness in MSM diagnosed with HIV infection at Melbourne Sexual Health Centre in Victoria has fallen dramatically between 2007 and 2016 and the proportion diagnosed with serological evidence of recent infection has increased. This effect is observed across all population subgroups and marks a positive milestone for the treatment as prevention paradigm.

Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator to supplement the HIV cascade: Dramatic fall from 2011 to 2015.

INTRODUCTION: The HIV care cascade is increasingly used to evaluate HIV treatment programs at the population level. However, the cascade indicators lack the ability to show changes over time, which reduces their utility to guide health policy. Alternatives have been proposed but are complex or result in a delay in results. We propose a new indicator of ART uptake, the time from HIV diagnosis to commencement of ART, and compare it to the existing cascade indicator of proportion of patients on treatment and the WHO proposed cohort cascade indicator of proportion of patients on treatment within one year of diagnosis. METHODS AND MATERIALS: Records from patients from the two largest HIV treatment centres in the state of Victoria, Australia (Melbourne Sexual Health Centre and The Alfred Hospital Department of Infectious Diseases) from 2011 to 2015 were extracted. The intervals between date of diagnosis, entry into care and initiation of ART were compared. RESULTS AND DISCUSSION: From 2011 to 2015 the proportion of in-care patients who were on ART rose from 87% to 93% (p<0.0001). From 2011 to 2014, the proportion of patients in care and on ART within one year of diagnosis increased from 43.4% to 78.9% (p = 0.001). The median time from diagnosis to ART fell from 418 days (IQR: 91-1176) to 77 days (IQR: 39-290)(p<0.001) by calendar year in which ART was commenced. CONCLUSIONS: From 2011 to 2015 there were substantial and clinically important falls in the median time from diagnosis to commencing ART in those that commenced ART. The size of this dramatic change was not apparent when only reporting the proportion of patients on ART. Time to ART is a useful indicator and can be used to supplement existing cascade indicators in measuring progress toward universal ART coverage.

Predictors and incidence of sexually transmitted Hepatitis C virus infection in HIV positive men who have sex with men.

BACKGROUND: Sexual transmission of Hepatitis C virus (HCV) in men who have sex with men (MSM) and its interaction with HIV status, sexually transmitted infections and sexual behaviour is poorly understood. We assessed the incidence and predictors of HCV infection in HIV positive MSM. METHODS: The electronic medical record and laboratory results from HIV positive MSM in care at a large urban public specialist HIV clinic embedded in a sexual health centre in Melbourne Australia were collected. Patients with two or more HCV antibody tests between January 2008 and March 2016 and with no record of injecting drug use were included. The HCV exposure intervals were the periods between a negative HCV test and the next HCV test. We compared HCV exposure intervals temporally associated with and without newly acquired syphilis or anorectal chlamydia. HCV exposure intervals were also categorised as being before or after HIV virological suppression and by most recent and nadir CD4 cell count. RESULTS: Thirty seven new HCV infections were diagnosed in 822 HIV positive MSM with no history of injecting drug use over 3114 person years (PY) of follow-up. Mean age was 43.1 years (±12.5) and mean CD4 cell count nadir was 362 cells/uL (±186). The incidence of HCV infection in the study population was 1.19/100PY (0.99-1.38). The incidence in exposure periods temporally close to new syphilis infection was 4.72/100PY (3.35-6.08) and to new anorectal chlamydia infection was 1.37/100PY (0.81-1.93). The incidence in men without supressed viral load was 3.19/100PY (1.89-4.49). In the multivariate Cox regression analysis only younger age (aHR 0.67 (0.48-0.92)), exposure periods temporally associated to new syphilis infection (aHR 4.96 (2.46-9.99)) and higher CD4 cell count nadir (aHR 1.26 per 100 cells/uL (1.01-1.58)) were associated with increased risk of HCV infection. During the study period the incidence of syphilis increased dramatically but the incidence of HCV infection remained the same. CONCLUSIONS: Incidence of HCV infection is associated with syphilis but not anorectal chlamydia which suggests a biological rather than behavioural risk modification. Rising syphilis incidence may offset declines in HCV transmission through HCV treatment as prevention.