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Increasing HIV testing frequency in gay and bisexual men (GBM) is critical to reducing the time between HIV infection and diagnosis. Using anonymous national behavioural surveillance data (2013–2018) from 43,753 surveys of Australian GBM, we examined HIV testing frequency trends and factors differentiating PrEP-users, non-PrEP-users reporting two or more tests in the previous year, and non-PrEP-users reporting less frequent testing. The proportion tested at least annually increased from 64.4% in 2013 to 70.8% in 2018 (p-trend

In Australia, HIV testing services have become increasingly available in non-traditional settings such as peer-led, community-based services to expand access and increase uptake of HIV testing among gay and bisexual men (GBM). This study aimed to compare the socio-demographic and behavioural characteristics of GBM whose last HIV test was conducted at a community-based service to GBM whose last test was at a traditional clinical setting. We analysed behavioural surveillance data collected from 5988 participants in seven states and territories in the period 2016-2017. We found that non-HIV-positive GBM who attended community-based services were largely similar to men attending clinic-based settings, particularly in terms of sexual practice and risk of HIV. However, non-HIV-positive GBM who were younger, born in Asia, more socially engaged with other gay men but who had not recently used PrEP were more likely to attend community-based services for their last HIV test. This study points to the successful establishment of community-based HIV testing services in Australia as a way to attract subgroups of GBM at potentially higher risk of HIV.

The prognostic role of c-Met expression in patients with head and neck cancer were controversial among different studies. Thus, we performed a meta-analysis to evaluate the relationships between c-Met expression and survival and clinical parameters of head and neck cancer patients. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between c-Met expression and overall survival (OS), and disease-free survival (DFS). Furthermore, odds ratios (ORs) and 95% CIs were used to describe the relationships between c-Met expression and different clinicopathological parameters. A total of 2417 patients from 19 studies were enrolled in the final analysis. The results showed that patients with higher c-Met expression had a poor OS (HR, 1.65; 95% CI, 1.20-2.27) and DFS (HR, 1.48; 95% CI, 0.99-2.20). In addition, c-Met expression was associated with the N classification of patients with head and neck cancer. These results suggested that c-Met expression was a risk factor for head and neck cancer, and increased c-Met expression would be a predictor of a poorer prognosis for the patients.

Recent increases in the availability of pre-exposure prophylaxis (PrEP) internationally have widened the range of HIV prevention strategies available to gay and bisexual men. This paper aimed to quantify the use of different risk reduction strategies and compare characteristics of men who rarely use any strategies with those who regularly use condoms or PrEP. Using national cross-sectional data from the Gay Community Periodic Surveys in Australia, comparisons were made between regular condom users (37.1% of participants), PrEP users (50.1%), and men who infrequently used any risk reduction strategies (12.8%). The proportion of gay and bisexual men reporting infrequent use of HIV risk reduction strategies has decreased in recent years. These men reported less frequent high-risk sexual practices than PrEP users and also reported less recent HIV testing than either PrEP or condom users. Men who infrequently use HIV risk reduction strategies should be encouraged to test for HIV more regularly and to utilise prevention strategies that align with their infrequent high-risk behaviour.

Background The exponential growth in the reach and development of new technologies over the past decade means that mobile technologies and social media play an increasingly important role in service delivery models to maximise HIV testing and access to treatment and care. This systematic review examines the impact of electronic and mobile technologies in medical care (eHealth) in the linkage to and retention of priority populations in the HIV treatment and care cascade, focussing on the Asia-Pacific region. Methods The review was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the Cochrane Collaboration guidelines. Both grey and published scientific literature from five different databases were searched for all original articles in English published from 2010 to 2017. Studies conducted outside the Asia-Pacific region or not including HIV priority populations were excluded. The methodological quality of studies included in the review was assessed using the Quality Assessment Tool for Quantitative Studies. Results The database search identified 7309 records. Of the 224 peer-reviewed articles identified for full text review, 16 studies from seven countries met inclusion criteria. Six cross sectional studies found evidence to support the use of eHealth, via text messages, instant messaging, social media and health promotion websites, to increase rates of HIV testing and re-testing among men who have sex with men (MSM). Evidence regarding the efficacy of eHealth interventions to improve antiretroviral treatment (ART) adherence was mixed, where one randomised controlled trial (RCT) showed significant benefit of weekly phone call reminders on improving ART adherence. Three further RCTs found that biofeedback eHealth interventions that provided estimated ART plasma concentration levels, showed promising results for ART adherence. Conclusions This review found encouraging evidence about how eHealth can be used across the HIV treatment and care cascade in the Asia-Pacific region, including increasing HIV testing and re-testing in priority populations as well as ART adherence. eHealth interventions have an important role to play in the movement towards the end of AIDS, particularly to target harder-to-reach HIV priority populations, such as MSM. Electronic supplementary material The online version of this article (10.1186/s12879-018-2972-5) contains supplementary material, which is available to authorized users.

SMS reminders sent to personal mobiles are increasingly used by clinical services to promote patient engagement, including adherence to antiretroviral treatment (ART) for HIV. From August to September 2015, a 6-week, randomised SMS reminder for ART adherence intervention was implemented among 98 HIV-positive clients of Australian's largest HIV charitable organisation located in Sydney. This was followed by a mixed-method evaluation, comprising a self-completed online survey and a one-to-one interview. Of the 62 survey participants, all being men, the majority were gay (85.5%) and living long-term with HIV (median year of HIV diagnosis = 1998). While everyone was on ART, a substantial proportion (n = 27, 43.5%) had interrupted treatment in the past. At the end of the intervention, based on the standard SMAQ measure, 82% had consistently adhered to ART in the previous week. While there was no statistically significant intervention effect, perceiving less stigma were independently associated with better ART adherence (adjusted odds ratio = 0.37; 95% CI 0.16-0.89; P = .026). Of the 11 interviewees, despite limited add-on effects on individual ART adherence, the campaign was well-received as a unique community support service. This study underscores the essential role of empowerment through enhancing disease self-management, increasing social support and reducing stigma, particularly for long-term HIV survivors. SMS messaging, part of mHealth, delivered by community services could have broader impacts on reducing health and social inequity.

Background The success of ‘treatment as prevention’ (TasP) to control HIV relies on the uptake of testing across priority population groups. Innovative strategies including; rapid HIV testing (RHT) in community and outreach settings, engaging peer service providers, and not requiring disclosure of sexual history have been designed to increase access. This paper reports on the implementation of ‘RAPID’, a community-based testing program in Queensland, Australia that employs these strategies to increase access to testing. Methods Service data, including client registration forms and a satisfaction survey from all clients attending RAPID between August 2014 and July 2015 were analysed. Results In 2014/2015 1,199 people attended RAPID to receive a free HIV test. The majority were urban-based gay men. 17.1% were first-time testers and 20.1% of participants were not eligible to access Medicare, Australia’s universal health care scheme. Conclusions RAPID’s evidence-based strategies appear to facilitate access to HIV testing, particularly among those who have never tested before; however the implications for the ongoing treatment and care of people ineligible for Medicare, who test positive to HIV warrants careful consideration. Electronic supplementary material The online version of this article (doi:10.1186/s12913-017-2249-5) contains supplementary material, which is available to authorized users.

The landscape of HIV testing has changed significantly in recent years following the rise in importance of the 'treatment as prevention' strategy and advancements in new HIV testing and prevention technologies. This review provides a synthesis of qualitative research findings published since 2010 on preferences and practices of men who have sex with men (MSM) surrounding HIV testing in high-income settings. MSM are one of the hardest groups to reach with standard or conventional HIV testing approaches. To develop innovative testing strategies for this particular group, a good understanding of their concerns, barriers and facilitators of accessing HIV testing is needed. This updated review provides valuable information for improving existing programs and designing new testing services for MSM.

Data from repeated, national behavioural HIV surveillance was used to identify similarities and differences between young gay and bisexual men (YGBM) aged 16–24 (n = 1608) and older GBM aged 25–49 (n = 6266), in order to quantify risks and identify gaps in HIV prevention. Trend analyses from 2014 to 2018 are also reported. While there were similar rates of condomless anal intercourse with casual partners in both age groups, YGBM had lower rates of HIV testing and PrEP use but also fewer male partners. Our results suggest most YGBM have lower HIV risk than older GBM but a minority merit enhanced testing and prevention efforts.

Objective The adenosine A1 receptor is a Gαi/o protein‐coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A1 receptors are implicated in the modulation of a variety of neuronal and synaptic activities. In this study, we investigated the role of A1 receptors in the regulation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in the adult rat brain in vivo. Methods Adult male Wistar rats were used in this study. After a systemic injection of the A1 antagonist DPCPX, rats were sacrificed and several forebrain regions were collected for assessing changes in phosphorylation of AMPA receptors using Western blots. Results A systemic injection of the A1 antagonist DPCPX induced an increase in phosphorylation of AMPA receptor GluA1 subunits at a PKA‐dependent site, serine 845 (S845), in the two subdivisions of the striatum, the caudate putamen, and nucleus accumbens. DPCPX also increased S845 phosphorylation in the medial prefrontal cortex (mPFC) and hippocampus. The DPCPX‐stimulated S845 phosphorylation was a transient and reversible event. Blockade of Gαs/olf‐coupled dopamine D1 receptors with a D1 antagonist SCH23390 abolished the responses of S845 phosphorylation to DPCPX in the striatum, mPFC, and hippocampus. DPCPX had no significant impact on phosphorylation of GluA1 at serine 831 and on expression of total GluA1 proteins in all forebrain regions surveyed. Conclusion These data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner., Our data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner.

Using repeated, cross-sectional behavioural surveillance data from Australia, we assessed trends in relationship agreements and casual sex among HIV-negative and untested gay and bisexual men who had regular partners during 2013–2018. We conducted three analyses: (i) trends in relationship agreements and casual sex over time; (ii) bivariate comparisons of PrEP users and non-PrEP-users to identify factors associated with PrEP use; and (iii) multivariate logistic regression to identify factors independently associated with PrEP use. The analysis of trends over time included 21,593 men, from which a sub-sample (n = 3764) was used to compare PrEP users and non-PrEP-users. We found a large increase in agreements that allowed condomless sex with casual partners, particularly by PrEP users in relationships (nearly 40% of whom had such an agreement). A further 34% of PrEP users reported having casual condomless sex without an agreement that permitted that behaviour, while 13% of non-PrEP-users also reported condomless sex with casual partners without an agreement. PrEP use was independently associated with having agreements permitting condomless sex with casual partners, recent condomless sex with casual partners, having greater numbers of male partners, recent post-exposure prophylaxis use, having an HIV-positive regular male partner, and recent condomless sex with regular male partners. Our findings show a shift away from relationship agreements in which condomless sex was only sanctioned between regular partners.

Background Sexually transmissible infections (STIs) continue to rise in people aged 15–29 in New South Wales (NSW), Australia (≥30,000 chlamydia (CT) notifications annually). However, STI testing rates are low and stigma remains about STI and testing. Methods Down to Test is a social marketing program targeting high-risk young people to improve attitudes and social norms for condom use and STI testing - facilitators for healthy sexual behaviour. The program includes information, blogs & forums at playsafe.health.nsw.gov.au and involves online marketing and face-to-face, peer-led music festival activations – an incentivised VIP area (clean toilets, phone charging, glitter bar, condoms) and access with a urine specimen for CT testing. Market segmentation research of values, attitudes and behaviours identified 2 high-risk groups of young people -‘experienced sex positive’ and ‘dominant risk-takers’. Program strategies and incentives were developed with these groups who identified peers to also help deliver the program. Results Between 9/2017 and 12/2018, 5783/124,000 (5%) young people registered for the VIP area during 7 NSW festivals. 189/5416 (3.5%) tested CT+. All CT- received SMS, 93% CT+ were informed & 75% confirmed treatment. Digital engagement metrics: 863,931 impressions, 1% Cut Through Rate for linked advertisements, 0.05% social engagement, and 5,000 peer educator conversations with campaign recall increase of 25%. Pre & post-intervention surveys showed increased social norms for STI testing (24% increase), positive attitudes (26%), and intention to STI test in the next 12 months (32%). Over 80% of participants were within the two high-risk groups. Conclusion Down to Test successfully engaged high risk young people attending music festivals and improved healthy sexual behaviour facilitators. Applying segmentation research and engaging the identified groups improved the likelihood of success by better targeting the activations. Broad reach across NSW was maximised by using festivals in a variety of locations. The program is adaptable to other locations. Disclosure No significant relationships.

BACKGROUND Prevalence of anxiety and mood disorders (AMDs) in HIV-infected individuals has varied widely because of the variety of measurements used and differences in risk factor profiles between different populations. We aimed to examine the relationship between HIV status and hospitalization for AMDs in gay and bisexual men (GBM). DESIGN AND METHODS HIV-infected (n = 557) and HIV-uninfected (n = 1325) GBM recruited in Sydney, Australia were probabilistically linked to their hospital admissions and death notifications (2000-2012). Random-effects Poisson models were used to assess HIV risk factors for hospitalization. Cox regression methods were used to assess risk factors for mortality. RESULTS We observed 300 hospitalizations for AMDs in 15.3% of HIV-infected and 181 in 5.4% of HIV-uninfected participants. Being infected with HIV was associated with a 2.5-fold increase in risk of hospitalization for AMDs in GBM. Other risk factors in the HIV-infected cohort included previous hospitalization for HIV-related dementia, a more recent HIV diagnosis, and a CD4 T-cell count above 350 cells per cubic millimeter. Being hospitalized for an AMD was associated with a 5.5-fold increased risk of mortality; this association did not differ by HIV status. An association between substance use and mortality was observed in individuals hospitalized for AMDs. CONCLUSIONS There is a need to provide more effective strategies to identify and treat AMDs in HIV-infected GBM. This research highlights the importance of further examination of the effects of substance use, neurocognitive decline, and AMDs on the health of HIV-infected individuals.

With the expanding pharmaceuticalization of public health, anthropologists have begun to examine how biomedicine's promissory discourses of normalization and demarginalization give rise to new practices of and criteria for citizenship. Much of this work focuses on the biomedicine-citizenship nexus in less-developed, resource-poor contexts. But how do we understand this relationship in resource-rich settings where medicines are readily available, often affordable, and a highly commonplace response to illness? In particular, what does it mean to not use pharmaceuticals for a treatable infectious disease in this context? We are interested in these questions in relation to the recent push for early and universal treatment for HIV infection in Australia for the twin purposes of individual and community health. Drawing on Ecks's concept of pharmaceutical citizenship, we examine the implications for citizenship among people with HIV who refuse or delay recommended medication. We find that moral and normative expectations emerging in the new HIV "treatment revolution" have the capacity to both demarginalize and marginalize people with HIV.

Obesity is an escalating global epidemic caused by an imbalance between energy intake and expenditure. (&minus, )-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to be conducive to preventing obesity and alleviating obesity-related chronic diseases. However, the role of EGCG in energy metabolism disorders and central nervous system dysfunction induced by a high-fat diet (HFD) remains to be elucidated. The aim of this study was to evaluate the effects of EGCG on brown adipose tissue (BAT) thermogenesis and neuroinflammation in HFD-induced obese C57BL/6J mice. Mice were randomly divided into four groups with different diets: normal chow diet (NCD), normal chow diet supplemented with 1% EGCG (NCD + EGCG), high-fat diet (HFD), and high-fat diet supplemented with 1% EGCG (HFD + EGCG). Investigations based on a four-week experiment were carried out including the BAT activity, energy consumption, mRNA expression of major inflammatory cytokines in the hypothalamus, nuclear factor-kappa B (NF-&kappa, B) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and immunofluorescence staining of microglial marker Iba1 in hypothalamic arcuate nucleus (ARC). Experimental results demonstrated that dietary supplementation of EGCG significantly inhibited HFD-induced obesity by enhancing BAT thermogenesis, and attenuated the hypothalamic inflammation and microglia overactivation by regulating the NF-&kappa, B and STAT3 signaling pathways.

Objectives There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. Methods We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. Results We observed 2032 hospitalisations in the HIV-negative cohort during 13 016 person-years (PYs) [crude rate: 15.6/100PYs (95% CI: 14.9–16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100PYs (95% CI: 36.6–39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91–2.86)] and the general population [SHR: 1.45 (95% CI: 1.33–1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67–0.78)]. The primary causes of hospitalisation differed between groups. Conclusions HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.

Background Blood-borne viruses (BBV) are prevalent among people with opioid dependence but their association with cause-specific mortality has not been examined at the population-level. Methods We formed a population-based cohort of 29,571 opioid substitution therapy (OST) registrants in New South Wales, Australia, 1993–2007. We ascertained notifications of infection and death by record linkage between the Pharmaceutical Drugs of Addiction System (OST data), registers of hepatitis C (HCV), hepatitis B (HBV) and human immunodeficiency virus (HIV) diagnoses, and the National Death Index. We used competing risks regression to quantify associations between notification for BBV infection and causes of death. BBV status, age, year, OST status, and OST episodes were modelled as time-dependent covariates; sex was a fixed covariate. Results OST registrants notified with HCV infection were more likely to die from accidental overdose (subdistribution hazard ratio, 95% Confidence Interval: 1.7, 1.5–2.0), cancer (2.0, 1.3–3.2) and unintentional injury (1.4, 1.0–2.0). HBV notification was associated with a higher hazard of mortality due to unintentional injury (2.1, 1.1–3.9), cancer (2.8, 1.5–5.5), and liver disease (2.1, 1.0–4.3). Liver-related mortality was higher among those notified with HIV only (11, 2.5–50), HCV only (5.9, 3.2–11) and both HIV and HCV (15, 3.2–66). Registrants with an HIV notification had a higher hazard of cardiovascular-related mortality (4.0, 1.6–9.9). Conclusions Among OST registrants, BBVs are a direct cause of death and also a marker of behaviours that can result in unintended death. Ongoing and enhanced BBV prevention strategies and treatment, together with targeted education strategies to reduce risk, are justified.

We investigated the racial or ethnic partner preferences among Australian gay and bisexual men (GBM) as part of a large study of sexual preferences among GBM, to identify whether racial bias was a factor in how GBM expressed their partner preferences. We surveyed 1853 Australian GBM about their partner preferences and preferred sex practices. We used logistic regression to identify whether factors such as age, gay social engagement, or men’s own ethnicity or race were associated with ethnic and racial partner preferences. Mean age was 34.8 years. Ethnic or racial background included: white or “Caucasian” (86.6%), Australian Aboriginal (2.7%), and Asian (6.6%). Mean attraction scores were highest for “Caucasian” men, and lowest for Aboriginal and Asian men. Under half (41.6%) were attracted to all racial or ethnic types; 7.7% were only attracted to “Caucasian” men. Being older and lower homonegativity scores were independently associated with finding all ethnic and racial types attractive. Being attracted only to “Caucasian” men was associated with younger age. Mental health was not associated with ethnic or racial partner preferences. Although men more commonly found most racial or ethnic types attractive, racial biases in partner selection were more evident among younger men, and among those who were less comfortable with their own sexuality. Addressing anti-gay stigma and broader exposure to gay community subcultures may be as important in countering racial bias.

Pre-exposure prophylaxis (PrEP) has been rapidly rolled out in large, publicly funded implementation projects in Victoria and New South Wales, Australia. Using behavioural surveillance of gay and bisexual men, we analysed the uptake and effect of PrEP, particularly on condom use by gay and bisexual men not using PrEP.We collected data from the Melbourne and Sydney Gay Community Periodic Surveys (GCPS), cross-sectional surveys of adult gay and bisexual men in Melbourne, VIC, and Sydney, NSW. Recruitment occurred at gay venues or events and online. Eligible participants were 18 years or older (face-to-face recruitment) or 16 years or older (online recruitment), identified as male (including transgender participants who identified as male); and having had sex with a man in the past 5 years or identified as gay or bisexual, or both. Using multivariate logistic regression, we assessed trends in condom use, condomless anal intercourse with casual partners (CAIC), and PrEP use by gay and bisexual men, controlling for sample variation over time.Between Jan 1, 2013, and March 31, 2017, 27 011 participants completed questionnaires in the Melbourne (n=13 051) and Sydney (n=13 960) GCPS. 16 827 reported sex with casual male partners in the 6 months before survey and were included in these analyses. In 2013, 26 (1%) of 2692 men reported CAIC and were HIV-negative and using PrEP, compared with 167 (5%) of 3660 men in 2016 and 652 (16%) of 4018 men in 2017 (p0·0001). Consistent condom use was reported by 1360 (46%) of 2692 men in 2013, 1523 (42%) of 3660 men in 2016, and 1229 (31%) of 4018 men in 2017 (p0·0001). In 2013, 800 (30%) of 2692 men who were HIV-negative or untested and not on PrEP reported CAIC, compared with 1118 (31%) of 3660 men in 2016, and 1166 (29%) of 4018 in 2017 (non-significant trend).A rapid increase in PrEP use by gay and bisexual men in Melbourne and Sydney was accompanied by an equally rapid decrease in consistent condom use. Other jurisdictions should consider the potential for community-level increases in CAIC when modelling the introduction of PrEP and in monitoring its effect.Australian Government Department of Health, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

Previous research indicates that stigma and discrimination have negative consequences for both healthcare delivery and for health outcomes of people who inject drugs (PWID). Also important but not as well researched is the association between perceived discrimination and increased engagement in risky behaviours. This research aimed to explore whether perceived discrimination from workers in Needle and Syringe programmes (NSPs) is associated with increased engagement in injecting risk practices such as the sharing of injecting equipment.Convenience sampling was used across eight NSP sites within Western Sydney, Australia. All clients who attended one of the NSPs were eligible to participate.A total of 236 clients completed the survey. Perceived discrimination from NSP staff was found to be significantly associated with some injecting risk practices. Respondents who reported greater perceived discrimination from NSP staff were significantly more likely to report being injected by someone else after they had injected themselves (OR 1.2, 95%CI 1.1-1.3) and reusing a needle or syringe (OR 1.1, 95%CI 1.0-1.3) in the last month. Although clients reported perceiving more discrimination from general health workers than from NSP workers (12.8 vs. 10.2, t=7.739, df=226, p0.001), perceived discrimination from general health workers was not associated with increased injecting risk practices.The findings of this study suggest that NSP workers need to be aware that although they work in a model that is usually non-judgemental, their clients may still have a heightened sensitivity to discrimination which can then have consequences for on-going engagement in risk practices.

usc Introduction: We conducted a detailed analysis of trends in new HIV diagnoses in Australia by country of birth, to understand any changes in epidemiology, relationship to migration patterns and implications for public health programs. Methods: Poisson regression analyses were performed, comparing the age-standardised HIV diagnosis rates per 100,000 estimated resident population between 2006–2010 and 2011–2015 by region of birth, with stratification by exposure (male-to-male sex, heterosexual sex–males and females). Correlation between the number of permanent and long-term arrivals was also explored using linear regression models. Results: Between 2006 and 2015, there were 6,741 new HIV diagnoses attributed to male-to-male sex and 2,093 attributed to heterosexual sex, with the proportion of diagnoses attributed to male-to-male sex who were Australian-born decreasing from 72.5% to 66.5%. Compared with 2006–2010, the average annual HIV diagnosis rate per 100,000 in 2011–15 attributed to male-to-male sex was significantly higher in men born in South-East Asia (summary rate ratio (SRR) = 1.37, p = 0.001), North-East Asia (SRR = 2.18, p

Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004-06 and 2011. In 2004-06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004-06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs.

An online survey was conducted among people living with HIV (PLHIV) in Australia to discern key factors associated with distinctive ART use patterns. The sample (N = 358), was further divided into three groups: those on ART continuously since initiation (n = 208, 58.1%); those on ART intermittently (n = 117, 32.7%); and those not on ART at the time of survey (n = 33, 9.2%). ART non-users were the most likely to hold serious concerns about ART that outweighed perceived necessities (benefits) from ART (AOR = 0.13; 95% CI 0.06–0.29; p

Smoking is an important factor that causes periodontitis, which manifests as alveolar bone injury and absorption, and has a high incidence and unfavorable treatment efficacy. Nicotine causes ischemia and inflammation of the periodontium and inhibits the mineralization of alveolar bones. Previous studies have revealed the anti‑tumor biological activities of catalpol, in addition to neuroprotection and anti‑inflammation. The present study therefore investigated the underlying protective mechanism of catalpol in alveolar bone injury. A total of 24 Wistar rats were infused with nicotine (0.7 mg/kg for 30 days), followed by subcutaneous injection of catalpol (2 µg/kg for 14 days). The loss of alveolar bone was examined, and bone alkaline phosphatase (AP) and osteocalcin levels were examined by ELISA. The expression of tumor necrosis factor (TNF)‑α and cyclooxygenase‑2 (COX‑2) was quantified by reverse transcription‑quantitative polymerase chain reaction analysis and western blotting. Treatment with nicotine decreased AP and osteocalcin levels, increased TNF‑α and COX‑2 expression levels, and led to alveolar bone loss compared with the control group. Catalpol decreased bone loss, increased AP and osteocalcin, and decreased TNF‑α and COX‑2 expression compared with the nicotine treatment group. Catalpol may alleviate nicotine‑induced injury and alveolar bone loss via inhibition of inflammatory factors, and facilitate the mineralization of alveolar bones.

Psychostimulants have an impact on protein synthesis, although underlying molecular mechanisms are unclear. Eukaryotic initiation factor 2α-subunit (eIF2α) is a key player in initiation of protein translation and is regulated by phosphorylation. While this factor is sensitive to changing synaptic input and is critical for synaptic plasticity, its sensitivity to stimulants is poorly understood. Here we systematically characterized responses of eIF2α to a systemic administration of the stimulant amphetamine (AMPH) in dopamine responsive regions of adult rat brains. Intraperitoneal injection of AMPH at 5 mg/kg increased eIF2α phosphorylation at serine 51 in the striatum. This increase was transient. In the medial prefrontal cortex (mPFC), AMPH induced a relatively delayed phosphorylation of the factor. Pretreatment with a dopamine D1 receptor antagonist SCH23390 blocked the AMPH-stimulated eIF2α phosphorylation in both the striatum and mPFC. Similarly, a dopamine D2 receptor antagonist eticlopride reduced the effect of AMPH in the two regions. Two antagonists alone did not alter basal eIF2α phosphorylation. AMPH and two antagonists did not change the amount of total eIF2α proteins in both regions. These results demonstrate the sensitivity of eIF2α to stimulant exposure. AMPH possesses the ability to stimulate eIF2α phosphorylation in striatal and mPFC neurons in vivo in a D1 and D2 receptor-dependent manner.

This study assesses association between CD4 level at initiation of antiretroviral treatment (ART) on subsequent treatment outcomes and mortality among people infected with HIV via various routes in Hunan province, China. Over a period of 10 years, a total of 7333 HIV-positive patients, including 553 (7.5%) MSM, 5484 (74.8%) heterosexuals, 1164 (15.9%) injection drug users (IDU) and 132 (1.8%) former plasma donors (FPD), were recruited. MSM substantially demonstrated higher initial CD4 cell level (242, IQR 167-298) than other populations (Heterosexuals: 144 IQR 40-242, IDU: 134 IQR 38-224, FPD: 86 IQR 36-181). During subsequent long-term follow up, the median CD4 level in all participants increased significantly from 151 cells/mm³ (IQR 43-246) to 265 cells/mm³ (IQR 162-380), whereas CD4 level in MSM remained at a high level between 242 and 361 cells/mm³. Consistently, both cumulative immunological and virological failure rates (10.4% and 26.4% in 48 months, respectively) were the lowest in MSM compared with other population groups. Survival analysis indicated that initial CD4 counts ≤ 200 cells/mm³ (AHR = 3.14; CI, 2.43-4.06) significantly contributed to HIV-related mortality during treatment. Timely diagnosis and treatment of HIV patients are vital for improving CD4 level and health outcomes.

We aimed to compare rates of illicit drug-related hospitalisations in HIV-negative (HIV−ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11–16, F18, F19), drug poisoning (T40–T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV−ve cohort [SIR 4.75 (95 % CI 3.30–6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92–5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01–3.46)], poly-drug use [IRR 2.17 (1.07–4.38)] and cannabis use [low use-IRR 1.95 (1.01–3.77), high use-IRR 2.58 (1.29–5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07–9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61–9.66), IRR 4.43(1.04–18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use.

Objective Three decades into the HIV epidemic and with the advancement of HIV treatments, condom and non-condom-based anal intercourse among gay men in resource-rich countries needs to be re-assessed. Methods The proportions of men engaging in a range of anal intercourse practices were estimated from the ongoing cross-sectional Gay Community Periodic Surveys in six states in Australia from 2007 to 2009. Comparisons were made between HIV-negative men, HIV-positive men with an undetectable viral load and those with a detectable viral load. Results Condoms play a key role in gay men’s anal intercourse practices: 33.8% of HIV-negative men, 25.1% of HIV-positive men with an undetectable viral load and 22.5% of those with a detectable viral load reported consistent condom use with all male partners in the 6 months before the survey. Among HIV-negative men, the second largest group were men who had unprotected anal intercourse (UAI) only in the context of HIV-negative seroconcordant regular relationships. Among HIV-positive men, the second largest group was men who had UAI in casual encounters preceded by HIV status disclosure to some, but not all, casual partners. Conclusions A minority, yet sizeable proportion, of men consistently engaged in a number of UAI practices in specific contexts, suggesting they have adopted deliberate HIV risk-reduction strategies. While it is important that HIV behavioural prevention continues to reinforce condom use, it needs to address both the challenges and opportunities of the substantial uptake of non-condom-based risk-reduction strategies.

Our aim was to clarify the role of alcohol and other drug (AOD) use in major depression among gay men attending general medical practices. A secondary analysis was conducted on survey data collected from 531 gay men attending high-HIV-caseload general practices in Adelaide and Sydney, Australia. The survey contained demographic, social, behavioural and AOD variables. Participants were classified into those with (n = 130) and without major depression (n = 401) using the PHQ-9 screening tool. Although rates of drug use were very high in the sample, multivariate logistic regression analysis showed that the majority of variables independently associated with major depression were social and behavioural factors. Only one AOD variable was associated with major depression: the use of three or more drug types in the past 6 months. Attending to specific patterns of AOD use may assist in the identification of gay men most at risk of major depression.

Analysis of cancer risk in primary immune deficiency (PID) offers insight into the relationship between immune function and cancer. Data on Australian patients (n = 1132) notified voluntarily to the Australasian Society of Clinical Immunology and Allergy PID Registry (1990-2008) were linked with national death and cancer registries. Person-years of follow-up commenced from up to 15 years before registration on the PID Registry or January 1982, the inception of national cancer registration. Site-specific, 5-year age-, sex-, calendar year–, and state-standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs) were calculated for all cancers except nonmelanocytic skin cancer. During an average of 16 person-years follow-up, a 1.6-fold excess relative risk of cancer was observed (n = 58; SIR 1.60, 95% CI 1.22-2.07) for all PID combined. Relative risk was increased for non-Hodgkin lymphoma (n = 16; SIR 8.82, 95% CI 5.04-14.30), leukemia (n = 4; SIR 5.36, 95% CI 1.46-13.73), and stomach cancer (n = 3; SIR 6.10, 95% CI 1.26-17.84). Excess cancer risk was observed for predominantly antibody deficiencies and other well-defined immunodeficiency syndromes. Results suggest that predominantly antibody deficiencies may be associated with a narrower range of solid cancers than immunodeficiency characterized by predominantly T-cell deficiency, such as iatrogenic and HIV-related immunodeficiency, although this requires confirmation in larger cohorts.

OBJECTIVE: To assess circumcision status as a risk factor for HIV seroconversion in homosexual men. DESIGN, SETTING AND PARTICIPANTS: The Health in Men (HIM) study was a prospective cohort of homosexual men in Sydney, Australia. HIV-negative men (n = 1426) were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. Participants underwent annual HIV testing, and detailed information on sexual risk behaviour was collected every 6 months. MAIN OUTCOME MEASURE: HIV incidence in circumcised compared with uncircumcised participants, stratified by whether or not men predominantly practised the insertive role in anal intercourse. RESULTS: There were 53 HIV seroconversions during follow-up; an incidence of 0.78 per 100 person-years. On multivariate analysis controlling for behavioural risk factors, being circumcised was associated with a nonsignificant reduction in risk of HIV seroconversion [hazard ratio 0.78, 95% confidence interval (CI) 0.42-1.45, P = 0.424]. Among one-third of study participants who reported a preference for the insertive role in anal intercourse, being circumcised was associated with a significant reduction in HIV incidence after controlling for age and unprotected anal intercourse (UAI) (hazard ratio 0.11, 95% CI 0.03-0.80, P = 0.041). Those who reported a preference for the insertive role overwhelmingly practised insertive rather than receptive UAI. CONCLUSIONS: Overall, circumcision did not significantly reduce the risk of HIV infection in the HIM cohort. However, it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse. Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men.

Ras-guanine nucleotide-releasing factors (Ras-GRFs) are densely expressed in neurons of the mammalian brain. As a Ras-specific activator predominantly concentrated at synaptic sites, Ras-GRFs activate the Ras-mitogen-activated protein kinase (Ras-MAPK) cascade in response to changing synaptic inputs, thereby modifying a variety of cellular and synaptic activities. While the Ras-MAPK cascade in the limbic reward circuit is well-known to be sensitive to dopamine inputs, the sensitivity of its upstream activator (Ras-GRFs) to dopamine remains to be investigated. In this study, the response of Ras-GRFs in their protein expression to dopamine stimulation was evaluated in the rat striatum in vivo. A single systemic injection of the psychostimulant amphetamine produced an increase in Ras-GRF1 protein levels in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum. The increase in Ras-GRF1 proteins was dose-dependent. The reliable increase was seen 2.5 h after drug injection and returned to normal levels by 6 h. In contrast to Ras-GRF1, protein levels of Ras-GRF2 in the striatum were not altered by amphetamine. In addition to the striatum, the medial prefrontal cortex is another forebrain site where amphetamine induced a parallel increase in Ras-GRF1 but not Ras-GRF2. No significant change in Ras-GRF1/2 proteins was observed in the hippocampus. These data demonstrate that Ras-GRF1 is a susceptible and selective target of amphetamine in striatal and cortical neurons. Its protein expression is subject to the modulation by acute exposure of amphetamine.

Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by a drop in extracellular pH. They are enriched in the mammalian brain with a high synaptic density. Accumulating evidence suggests that ASIC1 contributes to synaptic activity related to learning/memory and fear conditioning, and also plays critical roles in neurodegenerative diseases. In this study, we explored the effect of the psychostimulant, cocaine, on protein expression of ASICs in the mouse forebrain in vivo. We found that chronic systemic injection of cocaine (20 mg/kg, once daily for 5 consecutive days; 14 days of withdrawal) increased ASIC1, but not ASIC2, protein levels in the striatum, including the dorsal (caudate putamen) and the ventral (nucleus accumbens) striatum. No significant changes in ASIC1 or 2 protein levels in the median prefrontal cortex and the hippocampus were observed following the chronic cocaine administration. These data demonstrate that chronic cocaine exposure can upregulate ASIC expression in the striatum in a subunit-selective manner.

Objective To investigate the relationship between nonoccupational postexposure prophylaxis (NPEP) use and future HIV risk behaviours and HIV infection in a cohort of HIV-negative homosexual men in Sydney, Australia. Design Prospective analysis of NPEP use in a community cohort from 2001 to 2007. Methods In the Health in Men study cohort, men were annually questioned about NPEP use and tested for HIV. Every 6 months, detailed quantitative data on unprotected anal intercourse were collected. Cox regression models examined risk factors for incident NPEP use, HIV seroconversion and time trends in NPEP use. The change in the number of unprotected anal intercourse acts with nonseroconcordant partners before and after NPEP was examined using the Wilcoxon signed-rank test. Results One thousand four hundred and twenty-seven participants were enrolled. At baseline, 78.5% of participants had heard of NPEP, which increased to 97.4% by the fifth annual interview. NPEP use increased significantly from 2.9 per 100 person-years in 2002 to 7.1 per 100 person-years in 2007 (P = 0.007). Unprotected anal intercourse was a strong predictor of incident NPEP use. Use of NPEP was not associated with changes in HIV risk behaviour. Men who received NPEP had a significantly higher rate of subsequent HIV seroconversion (hazard ratio 2.67, 95% confidence interval 1.40-5.08, P = 0.003). Conclusion Awareness of the availability of NPEP in this cohort was nearly universal. Use was common and increased rapidly over the study period. NPEP was targeted mostly towards high-risk behaviours. Use of NPEP was not associated with reductions in risk behaviour, and men who received NPEP continued to be at high risk of subsequent HIV infection.

Introduction Sexual expression affects physical, mental and social well-being. There is a lack of understanding of male sexual dysfunction in homosexually active men. Aim We investigated gay men's self-report of a number of sexual problems. Methods The survey data were from a sample of 542 self-identified gay men, 40% of whom were HIV positive, recruited from six high HIV-caseload general practices in Australia. Main Outcome Measures The reporting of experiencing three or more sexual problems over a period of at least 1 month in the 12 months prior to a survey was defined here as having “multiple” sexual problems. We explored a number of factors, including HIV status, depression, alcohol and other drug use, and sexual risk-taking with casual male partners, in association with multiple sexual problems. Results Rates of a range of self-reported sexual problems were high, with erectile dysfunction and lack of sexual desire being the most commonly reported. These high rates were consistent with the limited data from previous Australian studies. Men who had multiple sexual problems were likely to suffer from major depression ( P P = 0.002). Factors independently associated with multiple sexual problems among the HIV-negative gay men were poorer general health and interpersonal isolation, whereas for the HIV-positive gay men, they were adoption of avoidant strategies to cope with daily life stress, sexual risk-taking in casual encounters, and the use of antidepressants. Conclusions Our findings underscore the complex interactions between depression, sexual dysfunction, sexual risk taking, HIV infection, and general well-being among homosexually active men. Mao L, Newman CE, Kidd MR, Saltman DC, Rogers GD, and Kippax SC. Self-reported sexual difficulties and their association with depression and other factors among gay men attending high HIV-caseload general practices in Australia. J Sex Med 2009;6:1378–1385.

Using two cohort studies (Health in men-HIM and positive health-PH) and repeated large cross-sectional surveys (Gay Community Periodic Survey-GCPS) of gay men in Sydney, Australia, we examined the association between viral load and unprotected anal intercourse (UAI) between HIV sero-discordant regular partners. Between 2001 and 2007, we conducted 243 interviews with 102 HIV-negative gay men in HIM and 148 interviews with 99 HIV-positive gay men in PH who were in regular relationships with HIV sero-discordant partners. During the same time period, 437 HIV positive men with HIV sero-discordant regular partners completed questionnaires for the GCPS. All completed interviews or questionnaires during that time period were used for these analyses. Amongst the HIV-negative respondents, sero-discordant UAI was more likely to be reported when the men believed their HIV-positive regular partner had an undetectable rather than a detectable viral load (P = 0.002). Amongst the HIV-positive respondents, sero-discordant UAI was as likely to be reported when they themselves reported having an undetectable or a detectable viral load. Use of viral load in negotiating condom use between sero-discordant gay couples may be understood very differently by the HIV-negative and HIV-positive men within those partnerships.

OBJECTIVES: Social factors associated with Major Depressive Disorder (MDD) were identified among gay men attending high HIV caseload general practices in Sydney and Adelaide. METHODS: Men who visited four participating practices were invited to self-complete a survey. A self-screening tool (PHQ-9), based on the Diagnostic and Statistical Manual of Mental Disorders, version four (DSM-IV), was used to measure depressive disorders. RESULTS: The rate of MDD (PHQ-9 score 10 or above) among the 195 HIV-positive gay men was significantly higher than that among the 314 non-HIV-positive gay men (31.8% vs 20.1%, p=0.002). Current MDD was independently associated with younger age, lower income, recent major adverse life events, adopting denial and isolation as coping strategies, less social support, less gay community involvement and recent sexual problems. HIV-status, however, was not independently associated with MDD. CONCLUSION: Socio-economic hardship, interpersonal isolation and personal withdrawal were significantly and independently associated with major depression in this population of gay men. Implications: The study provides further evidence of health inequity affecting gay men in Australia. Structural health promotion approaches focused on homophobia and discrimination, as well as community-engaged primary health care responses are called for to mitigate this inequity.

BACKGROUND: In contrast to the broad literature on depression in the general population, little is known about the management of depression affecting gay men and HIV-positive men attending general practice clinics. OBJECTIVE: This paper explores qualitative descriptions of how depression in gay men and HIV-positive men is managed by GPs. METHODS: As part of the qualitative component of a mixed method study on HIV and depression, semi-structured interviews were conducted with 16 GPs in three geographical settings in Australia: Sydney, Adelaide and a rural coastal town. RESULTS: GPs identified a range of features in their experience of managing depression in gay men and in HIV-positive men. Some were common to the care of other groups with depression, but this paper reports on features unique to this patient group. These include capitalizing on the high frequency of contact with this patient group, taking advantage of the specialist multidisciplinary teams who provide support, building upon the unusual willingness of this patient group to take medication, appreciating the central importance to many gay men of sexual functioning, and recreational drug use, responding to social isolation in this patient group and coping with increasing challenges for the HIV general practice workforce. CONCLUSIONS: Despite the identification of several key strengths in working with this patient group, the ability of GPs to develop their capacity to manage depression in gay men and men with HIV is uncertain in the context of a growing range of challenges for GPs in both mental health and HIV care.

Background.Criteria for antiretroviral treatment (ART) were adjusted to enable early HIV treatment for people living HIV/AIDS (PLHIV) in China in recent years. This study aims to determine how pretreatment waiting time after HIV confirmation affects subsequent adherence and outcomes over the course of treatment.Methods.A retrospective observational cohort study was conducted using treatment data from PLHIV in Yuxi, China, between January 2004 and December 2015.Results.Of 1,663 participants, 348 were delayed testers and mostly initiated treatment within 28 days. In comparison, 1,315 were nondelayed testers and the median pretreatment waiting time was 599 days, but it significantly declined over the study period. Pretreatment CD4 T-cell count drop (every 100 cells/mm3) contributed slowly in CD4 recovery after treatment initiation (8% less,P<0.01) and increased the risk of poor treatment adherence by 15% (ARR = 1.15, 1.08–1.25). Every 100 days of extensive pretreatment waiting time increased rates of loss to follow-up by 20% (ARR = 1.20, 1.07–1.29) and mortality rate by 11% (ARR = 1.11, 1.06–1.21), based on multivariable Cox regression.Conclusion.Long pretreatment waiting time in PLHIV can lead to higher risk of poor treatment adherence and HIV-related mortality. Current treatment guidelines should be updated to provide ART promptly.

Psychostimulants activate the Ras-mitogen-activated protein kinase (Ras-MAPK) cascade in the limbic reward circuit and thereby trigger a transcription-dependent mechanism underlying enduring synaptic plasticity related to addictive properties of drugs of abuse. The Ras-specific activator, Ras-guanine nucleotide-releasing factor (Ras-GRF), is predominantly expressed at synapses and is thought to actively regulate Ras-MAPK responses to changing synaptic signals. In this study, a possible influence of cocaine on Ras-GRF gene expression at the protein level in the rat striatum was investigated in vivo. A single systemic injection of cocaine induced an increase in Ras-GRF1 protein levels in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum. The increase in Ras-GRF1 proteins was dose-dependent and was a delayed and transient event. In contrast to Ras-GRF1, a closely related Ras-GRF2 showed no change in its protein abundance following cocaine administration. These data identify the Ras activator, Ras-GRF1, although not Ras-GRF2, as a susceptible target to cocaine stimulation in striatal neurons.

Introduction : Studies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments in reducing HIV transmission risk. However, there are limited data regarding the effect of treatment on HIV transmission in homosexual male couples. We examined features of male homosexual HIV serodiscordant relationships that may impact upon the design of HIV treatment and transmission studies. Methods : Data were from a prospective cohort study of HIV-negative homosexual men in Sydney, Australia. Men were followed up with six-monthly interviews and annual testing for HIV. Characteristics of men in HIV serodiscordant and seroconcordant relationships at baseline were compared, and a longitudinal analysis performed of rate of relationship break-up and of HIV incidence. Results : At baseline, 5.5% of participants ( n =79) had an HIV-positive partner. Most (80.8%) of these relationships were non-monogamous, and 36.7% of men reported recent unprotected anal intercourse (UAI) with casual partners. The rate of relationship break-up was 29.5 per 100 person-years. Half of men in serodiscordant relationships (49.4%) reported recent UAI with their regular partners. HIV incidence was 2.2 per 100 person-years. It was substantially higher in relationships of less than one year’s duration (6.1 per 100 person-years) and in men who reported unprotected receptive anal intercourse with ejaculation with their regular partners (15.5 per 100 person-years). Conclusions : Levels of HIV transmission risk and incidence were high, particularly in early relationships. Rates of relationship break-up were high. These data suggest that studies of HIV treatments and transmission in homosexual serodiscordant couples should focus on early relationships so as not to underestimate risk, and sample sizes must allow for high rates of relationship break-up. Keywords: HIV treatment as prevention; men who have sex with men; homosexual men; serodiscordant couples; HIV viral load; HIV transmission. (Published: 25 May 2015) Citation: Bavinton BR et al. Journal of the International AIDS Society 2015, 18 :19884 http://www.jiasociety.org/index.php/jias/article/view/19884 | http://dx.doi.org/10.7448/IAS.18.1.19884

Current debates regarding the use of antiretroviral therapy (ART) to promote both individual- and population-level health benefits underscore the importance of understanding why a subpopulation of people with diagnosed HIV and access to treatment choose not to use it. Semi-structured interviews were conducted between 2012 and 2014 with 27 people living with HIV in Australia who were not using ART at the time of interview. Analytic triangulation permitted an appreciation of not only the varied personal reasons for non-use of treatment, but also underlying views on HIV treatment, and the ideal conditions imagined necessary for treatment initiation. Policy goals to increase the number of people with HIV using ART must recognize the diverse explanations for non-use of ART, which include concerns about the various impacts of committing to lifelong pharmaceutical treatment use. Our research identified distinctive subgroups among people who are not using antiretroviral therapy, with a range of individual and social needs that may affect treatment decisions. These findings challenge assumptions about treatment non-use in resource-rich settings, revealing persistent consumer fears about the potent and unknown effects of HIV medications that deserve greater recognition in policy debate on treatment uptake.

Background: Early detection and treatment of bacterial sexually transmitted infections has been advocated as an HIV prevention strategy. Aim: To inform screening guidelines, the incidence and risk factors for urethral and anal gonorrhoea and chlamydia were studied in a prospective cohort of community-based HIV negative homosexual men in Sydney, New South Wales, Australia. Methods: All participants were offered annual screening for gonorrhoea and chlamydia (study-visit diagnoses) on urine and anal swabs using nucleic acid amplification. Participants also reported diagnoses of gonorrhoea and chlamydia made elsewhere between interviews (interval diagnoses). All diagnoses were summed to create a combined incidence rate, and detailed data on specific sexual practices with casual and regular partners were collected. Results: Among 1427 men enrolled, the combined incidence rates were 3.49 and 2.96 per 100 person-years for urethral and anal gonorrhoea, respectively; and 7.43 and 4.98 per 100 person-years for urethral and anal chlamydia, respectively. Urethral infections were associated with unprotected anal intercourse (UAI) with HIV-positive partners (hazard ratio (HR) = 2.58, 95% CI 1.10 to 6.05 for urethral gonorrhoea) and with frequent insertive oral sex (p for trend 0.007 for urethral chlamydia). Anal infections were associated with receptive UAI (p for trend 0.001 for both anal gonorrhoea and chlamydia) and other receptive anal sexual practices. Stratified analyses showed the independence of the associations of insertive oral sex with urethral infections and of non-intercourse receptive anal practices with anal infections. Conclusion: Incident gonorrhoea and chlamydia were common. Risk behaviours for both urethral and anal infections were not restricted to UAI. Screening that includes tests for anal and urethral infections should be considered for all sexually active homosexual men, not just for those who report UAI.

This paper reports on the breaking of agreements between regular partners among HIV-negative gay men in Sydney. Data were from the 1333 men completing face-to-face interviews through December 2003 for the Health in Men (HIM) open cohort of HIV-negative gay men in Sydney.822 men had a primary regular partner during the six month period before their 2003 interview. Most of these men had entered into agreements with their partners about sex either with each other or with other partners (87.2%). They most commonly agreed not to use condoms with each other (50.6%). Regarding casual sex, they most commonly agreed to always use condoms (34.2%) or to have no sex with men outside their relationships (28.6%). 48.8% reported some discomfort discussing with their partner their sex outside the relationship. Among those with agreements with their partners, 27.7% reported ever breaking those agreements. Those who found it more difficult to discuss issues of HIV serostatus and sexuality were more likely to report having broken their agreements (p.001; p=.021 at one-year follow-up) and were more likely to have engaged in unprotected anal intercourse with casual partners (p.001). A third of those men who broke their agreements did not inform their partner. A substantial proportion of gay men with agreements with their regular partners report some discomfort discussing sexuality and HIV serostatus with their partners. Difficulty discussing these issues may place these men at increased risk of breaking their agreements and may place both themselves and their partners at increased risk of infection.

Increasing evidence suggests an active participation of nociceptinergic transmission in the central control of cardiovascular activity and reflex. In this study, the role of the classic opioid mu receptor and the nociceptin/orphanin FQ receptor, a novel opioid receptor, in the nucleus tractus solitarii (NTS) in the regulation of cardiovascular activity was investigated and compared in chronically cannulated and freely moving conscious rats. Microinjections of nociceptin, an endogenous ligand for the nociceptin receptor, into the relatively rostral NTS produced dose-related (0.04, 0.2, and 1 nmol) increases in blood pressure and heart rate. Intra-NTS injection of the selective nociceptin receptor antagonist [Nphe(1)]Nociceptin(1-13)NH(2) (NOR-AN) at 1 nmol blocked the increases in blood pressure and heart rate induced by nociceptin. In contrast, pretreatment with the nonselective opioid receptor antagonist naloxone (5 nmol) had no effects on the cardiovascular responses to nociceptin. Like nociceptin, microinjection of endomorphin-1 (EM-1), an endogenous ligand for the opioid mu receptor, into the rostral NTS increased blood pressure and heart rate in a dose-dependent manner (0.04, 0.2, and 1 nmol). Pretreatment with naloxone (5 nmol), but not NOR-AN, blocked cardiovascular responses elicited by EM-1. Neither NOR-AN nor naloxone alone had significant effects on the baseline blood pressure and heart rate. Injection of excitatory amino acid l-glutamate (1 nmol) into the same sites caused the typical depressor and bradycardic responses. In the caudal NTS areas, nociceptin and EM-1 seemed to induce opposite responses: hypotension and bradycardia. These results suggest that the novel nociceptin receptors and traditional opioid receptors in the NTS may be independently involved in the regulation of cardiovascular activity.

The Galphaq protein-coupled metabotropic glutamate receptor subtype-5 (mGluR5) is densely expressed in medium spiny projection neurons of striatum. Emerging evidence suggests a significant role of mGluR5 in the addictive plasticity of striatal neurons that is likely derived from inducible cellular gene expression related to stimulation of mGluR5 and associative signaling proteins. In this study, we found that activation of mGluR5 with a selective agonist (RS)-2-chloro-5-hydroxy-phenylglycine (CHPG) induced a rapid and transient phosphorylation of a transcription regulator Elk-1 in cultured striatal neurons from rat E19 embryos or neonatal day-1 pups. The Elk-1 phosphorylation was dose-dependent and occurred in neurochemically identified GABAergic neurons, but not glia. A series of experiments further demonstrated that the CHPG-stimulated Elk-1 phosphorylation was mediated through selective activation of mGluR5-regulated phospholipase C and associative second messenger system, i.e. 1,4,5,-triphosphate-sensitive Ca2+ release. Moreover, the Elk-1 phosphorylation was partially dependent on mGluR5-mediated co-activation of NMDA, but not kainate/AMPA receptors and L-type voltage-operated Ca2+ channels. Using an immediate early gene c-fos as a report of inducible gene expression, we found that CHPG induced marked c-fos mRNA expression. The c-fos induction kinetically corresponded to the Elk-1 phosphorylation and was attenuated by antisense oligonucleotides that selectively knocked down Elk-1 proteins. These results indicate that glutamatergic tone on mGluR5 is positively coupled to Elk-1 phosphorylation in striatal neurons via multiple signaling mechanisms involving Ca2+ release and NMDA activation, and the mGluR5-mediated Elk-1 phosphorylation facilitates gene transcription.

Objectives: We quantified concomitant medication polypharmacy, pharmacokinetic and pharmacodynamic interactions, adverse effects and adherence in Australian adults on effective antiretroviral therapy. Design: Cross-sectional. Methods: Patients recruited into a nationwide cohort and assessed for prevalence and type of concomitant medication (including polypharmacy, defined as ≥5 concomitant medications), pharmacokinetic or pharmacodynamic interactions, potential concomitant medication adverse effects and concomitant medication adherence. Factors associated with concomitant medication polypharmacy and with imperfect adherence were identified using multivariable logistic regression. Results: Of 522 participants, 392 (75%) took a concomitant medication (mostly cardiovascular, nonprescription or antidepressant). Overall, 280 participants (54%) had polypharmacy of concomitant medications and/or a drug interaction or contraindication. Polypharmacy was present in 122 (23%) and independently associated with clinical trial participation, renal impairment, major comorbidity, hospital/general practice-based HIV care (versus sexual health clinic) and benzodiazepine use. Seventeen participants (3%) took at least one concomitant medication contraindicated with their antiretroviral therapy, and 237 (45%) had at least one pharmacokinetic/pharmacodynamic interaction. Concomitant medication use was significantly associated with sleep disturbance and myalgia, and polypharmacy of concomitant medications with diarrhoea, fatigue, myalgia and peripheral neuropathy. Sixty participants (12%) reported imperfect concomitant medication adherence, independently associated with requiring financial support, foregoing necessities for financial reasons, good/very good self-reported general health and at least 1 bed day for illness in the previous 12 months. Conclusion: In a resource-rich setting with universal healthcare access, the majority of this sample took a concomitant medication. Over half had at least one of concomitant medication polypharmacy, pharmacokinetic or pharmacodynamic interaction. Concomitant medication use was associated with several adverse clinical outcomes.

Background Routine HIV clinical monitoring is vital for people living with HIV (PLHIV) after treatment initiation. The relationship between clinical visits during the first 6 months after initial antiretroviral therapy (ART) and long-term, HIV-related mortality and service retention was investigated. Methods: A retrospective ART observational research database was established based on de-identified data extracted from 6959 records of adult HIV-positive registrants held by Hunan CDC (Center for Disease Control and Prevention) between 2003 and 2013. Results: During the first 6 months of initiation into ART, 2364 (34.0%) of PLHIV had completed four scheduled visits, meeting the Chinese ART clinical monitoring standards. From 6 months onwards (up to 36 months), this group had the lowest HIV-related mortality (4.4%) compared with those who had more or less than four kept visits in the first 6 months [one visit only: adjusted hazards ratio (AHR) = 3.15, 95% CI 2.24–3.88; two visits: AHR = 2.24, 95% CI 1.80–3.01; three visits: AHR = 1.86, 95% CI 1.69–2.05; and >4 visits: AHR = 1.37, 95% CI 1.11–1.72]. Those with less than three kept visits were also at increased risk of cohort loss to follow up (ART discontinuation, prolonged service disengagement or death). A myriad of personal, clinical and social factors are identified to be associated with increased HIV-related mortality and clinical retention. Conclusions: Enabling PLHIV to complete four scheduled clinical visits during the first 6 months of ART initiation, as recommended by the Chinese CDC, is critical.

Malignant oral ulcers are common pathological occurrence in oral and maxillofacial tumors. A noninvasive method for diagnosis of malignant oral ulcers was developed in the study, which is based on hematoporphyrin monomethylether (HMME) fluorescence spectroscopy. The objective of this work is to determine the feasibility of this method in differentiating the malignant tissues from the inflammatory ones in the hamster cheek pouch model. Adult hamsters were used for the study and a cheek pouch model was established. For the malignant model, the 9, 10-dimethyl-1, 2-benzanthracene carcinogenesis was applied to one cheek pouch for 10 weeks (N = 35). The simple ulcers were created on buccal cheek mucosa in a simple manner (N = 10). Prior to sacrifice, HMME solution was injected into the tissues. The induced fluorescence spectra of the cheek tissues were recorded by a fiber spectrometer with excitation at 405 nm. A spectral algorithm was used to eliminate the effect of autofluorescence, and a spectral parameter S was selected as diagnostic criterion. After fluorescence measurement, the animals were sacrificed and the measured tissues were collected. Histological staining was performed and the results of histopathological evaluation were documented. The diagnostic criteria that reflected the fluorescence intensity were set as follows: normal, S ≤ 10; simple ulcer, 230 ≤ S ≤ 290; and malignant ulcer, 140 ≤ S ≤ 200. The sensitivity and specificity of this detection method was verified by scalpel biopsy, and the overall accuracy was over 90 %. The results of this study showed that the fluorescence spectroscopic method implemented by HMME can accurately differentiate the two kinds of clinically indistinguishable diseases.