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Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals.

Objectives: The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. Methods: A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982–1995, 1996–1999, 2000–2004, 2005–2008 and 2009–2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. Results: For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend < 0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend < 0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. Conclusions: Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

BACKGROUND: Preexposure prophylaxis (PrEP) prevents HIV infection but relies on good adherence at times of risk, termed "prevention-effective adherence." Most studies assess adherence without reference to sexual behaviur, making it challenging to determine if poor adherence coincides with HIV risk. SETTING: We examined data from a behavioral substudy of a large-scale PrEP implementation trial in New South Wales, Australia. METHODS: Trial participants completed optional brief quarterly surveys, reporting the number of pills taken and sexual behavior with male partners for each day of the "last full week" before each survey. Condomless sex (CLS) was defined as "higher risk" for HIV when with HIV-positive men with detectable/unknown viral loads or unknown HIV status men. Adequate PrEP protection was defined as ≥4 pills for participants assigned male sex at birth and ≥6 pills for participants assigned female sex at birth (including transgender men). RESULTS: Of 9596 participants dispensed PrEP, 4401 completed baseline and ≥1 follow-up survey. Participants reported on 12,399 "last full weeks": 7485 weeks (60.4%) involved CLS and 2521 weeks (33.7% of CLS-weeks) involved higher risk CLS. There were 103 weeks in which participants did not have adequate PrEP protection and had higher risk CLS: 4.1% of higher-risk CLS weeks (n = 103/2521), 1.4% of all CLS weeks (n = 103/7485), and 0.8% of all observed weeks (n = 103/12,399). CONCLUSIONS: In a large PrEP trial, prevention-effective adherence to PrEP was very high at 99%. Our findings illustrate the importance of measuring pill-taking and sexual behavior in the same period so that prevention-effective adherence can be better estimated.

Background: Anal symptoms may indicate serious pathology. Receptive anal intercourse (RAI) and sexually transmissible infections (STIs) may contribute to a higher prevalence of symptoms among gay and bisexual men (GBM). This study investigated associations with anal symptoms among GBM. Methods: The Study of the Prevention of Anal Cancer was a longitudinal study of anal human papillomavirus and related lesions in Sydney, Australia. GBM aged ≥35 years were recruited from community settings between September 2010 and August 2015. Information about anal symptoms (discharge, itch, pain defecating, lump, bleeding, 'sores', tearing, tenesmus), STIs and sexual behaviours was collected. High-resolution anoscopy (HRA) and STI testing were performed. Logistic regression analyses on baseline data were performed to assess associations with each symptom. Results: Among 616 participants (median age 49 years, 35.9% HIV positive), 35.3% reported at least one anal symptom within the past week and 65.3% were diagnosed with fistula, fissure, ulcer, warts, haemorrhoids and/or perianal dermatoses at HRA. Anal symptoms were not associated with anal chlamydia, gonorrhoea, warts or syphilis. Self-reported 'sores' were associated with previous anal herpes simplex virus (HSV; P < 0.001). 'Sores' (P < 0.001), itch (P = 0.019), discharge (P = 0.032) and lump (P = 0.028) were independently associated with ulceration. Among participants diagnosed with fissure, fistulae, haemorrhoids and perianal dermatoses, 61.9%, 100%, 62.0% and 63.9% respectively were asymptomatic. Only self-reported anal tear was independently associated with recent RAI. Conclusions: Previous anal HSV was the only STI associated with any symptom. Anal pathology was highly prevalent, but often asymptomatic. Anal symptoms do not appear to be useful markers of most anal pathology in GBM.

OBJECTIVE: High-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia. METHODS: GBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method. RESULTS: Between 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43-56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (p<0.001), having a higher number of recent RAI partners regardless of condom use (p<0.001 for both), preference for the receptive position during anal intercourse (p=0.014) and other non-intercourse receptive anal sexual practices, including rimming, fingering and receptive use of sex toys (p<0.05 for all). In multivariable analyses, being HIV-positive (HR 1.46, 95% CI 1.09 to 1.85, p=0.009) and reporting condom-protected RAI with a higher number of sexual partners (p<0.001) remained significantly associated with incident HRHPV. When stratified by recent RAI, non-intercourse receptive anal practices were not associated with incident HRHPV in men who reported no recent RAI. CONCLUSION: GBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually

OBJECTIVE: Examine the changes in service delivery Australian public sexual health clinics made to remain open during lockdown. METHODS: A cross-sectional survey designed and delivered on Qualtrics was emailed to 21 directors of public sexual health clinics across Australia from July-August 2020 and asked about a variety of changes to service delivery. Descriptive statistics were calculated. RESULTS: Twenty clinics participated, all remained open and reported service changes, including suspension of walk-in services in eight clinics. Some clinics stopped offering asymptomatic screening for varying patient populations. Most clinics transitioned to a mix of telehealth and face-to-face consultations. Nineteen clinics reported delays in testing and 13 reported limitations in testing. Most clinics changed to phone consultations for HIV medication refills (n=15) and eleven clinics prescribed longer repeat prescriptions. Fourteen clinics had staff redeployed to assist the COVID-19 response. CONCLUSION: Public sexual health clinics pivoted service delivery to reduce risk of COVID-19 transmission in clinical settings, managed staffing reductions and delays in molecular testing, and maintained a focus on urgent and symptomatic STI presentations and those at higher risk of HIV/STI acquisition. Implications for public health: Further research is warranted to understand what impact reduced asymptomatic screening may have had on community STI transmission.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

Objectives Pharyngeal gonorrhoea disproportionately affects men who have sex with men (MSM). We explored temporal trends in pharyngeal gonorrhoea positivity among MSM compared with anorectal and urogenital positivity. Methods Data (2011-2015) were extracted from 41 publicly funded sexual health clinics participating in a national surveillance network. Positivity was defined as the proportion of first-visit testing occasions where gonorrhoea was detected. Logistic regression explored trends in positivity and correlates of positive pharyngeal tests. Results From 2011 to 2015, 24 792 MSM tested (16 710 pharyngeal, 19 810 urogenital and 15 974 anorectal first-visit tests). Pharyngeal positivity increased by 183% from 139/3509 (4.0%) in 2011 to 397/3509 (11.3%) in 2015, p-trend <0.001; urogenital positivity by 39% from 257/4615 (5.6%) to 295/3783 (7.8%), p-trend=0.006; and anorectal positivity by 87% from 160/3469 (4.6%) to 286/3334 (8.6%), p-trend <0.001. The annual temporal increase in positivity was greater in the pharynx (OR 1.33; 95% CI 1.27 to 1.38) than at urogenital (OR 1.06; 95% CI 1.02 to 1.10) and anorectal (OR 1.16; 95% CI 1.11 to 1.21) sites. Factors independently associated with pharyngeal gonorrhoea were: younger age (p<0.001), higher numbers of recent sexual partners (p-trend=0.004), contact with a person with a diagnosed STI (p<0.001), injecting drug use (p<0.001), anogenital symptoms (p<0.001) and HIV-positive status (p=0.050). Conclusion Temporal increases in gonorrhoea positivity occurred at all anatomical sites, with the greatest increase in the pharynx. Risk factors could be used to help to develop testing and prevention strategies among MSM at highest risk. Strengthening sexual health service delivery, testing and surveillance remain priorities for pharyngeal gonorrhoea control.

Background The resumption of sexual activity shortly after commencing treatment for sexually transmitted infections (STIs) is poorly described despite contributing to onward transmission. With azithromycin remaining an option for rectal Chlamydia trachomatis, resuming sex too early after treatment may contribute to antimicrobial resistance because of exposure of newly acquired STIs to subinhibitory concentrations. Methods Clinical and sexual behavioral data were collected from men participating in a trial assessing treatment efficacy for rectal chlamydia. Data were collected at recruitment and weekly for 3 weeks after commencing treatment. Outcome measures were resumption of any sexual activity or condomless receptive anal sex within 1, 2, or 3 weeks after commencing treatment. Generalized linear regression was used to calculate adjusted risk ratios (aRR) to identify associated factors. Results Almost 1 in 10 men (9.5%; 95% confidence interval [CI], 7.2-12.1) resumed condomless receptive anal sex within 1 week of commencing treatment. This was associated with current preexposure prophylaxis use (aRR, 3.4; 95% CI, 2.5-4.8]) and having 9 or more sexual partners in the last 3 months (aRR, 3.2; 95% CI, 1.6-5.0). Most men (75.0%; 95% CI, 71.3-78.5) resumed any sexual activity within 3 weeks; this was associated with a greater number of sexual partners (4-8 partners; aRR, 1.2; 95% CI, 1.1-1.5; ≥9 partners; aRR, 1.5; 95% CI, 1.3-1.7). Conclusions Resuming condomless receptive anal sex early after treatment may facilitate onward transmission and promote antimicrobial resistance for STIs. Although azithromycin remains a treatment option, this analysis highlights the need for new health promotion messages regarding early resumption of sex and continued surveillance for antimicrobial resistance.

Background:Anal cancer incidence increased markedly in people living with HIV (PLWHIV) after the introduction of HAART, but in a few setting settings, recent declines have been reported. We report the incidence and time trends of anal cancer in PLWHIV in Australia.Study design:A data linkage study between the National HIV Registries and the Australian Cancer Database.Methods:Cases of anal squamous cell carcinoma (ASCC) in Australians aged 16 years and above diagnosed with HIV between 1982 and 2012 were identified. Standardized incidence ratios (SIRs) were calculated to compare incidence with that of the general population. Poisson regression models were developed to describe the time trends of ASCC over time and to compare ASCC risk within subgroups of PLWHIV.Results:Among 28696 individuals, a total of 129 cases of ASCC were identified. The crude incidence was 36.3 per 100000 person-years and it increased sharply from 14.8 to 62.1 per 100000 person-years between 1982-1995 and 2009-2012 (P trend <0.001). The SIR was 35.3 (95% confidence interval 29.5-42.0), and there was an inverse association between SIR and increasing age (P trend <0.001). In multivariate analyses, ASCC incidence was significantly higher in recent years (P trend <0.001), in those who acquired HIV through male homosexual contact (P=0.002), and in those who had a history of AIDS (P<0.001).Conclusion:PLWHIV in Australia are at markedly higher risk of anal cancer. Unlike in some industrialized countries with a mature HIV epidemic, the incidence of anal cancer is still increasing in this population in Australia.

Introduction: There are few data about the range of strategies used to prevent sexual HIV transmission within gay male serodiscordant couples. We examined HIV prevention strategies used by such couples and compared differences between countries. Methods: Opposites Attract was a cohort study of male serodiscordant couples in Australia, Brazil and Thailand, from May 2014 (Australia) or May 2016 (Brazil/Thailand) to December 2016. At visits, HIV-positive partners had viral load (VL) tested; HIV-negative partners reported sexual behaviour and perceptions of their HIV-positive partner's VL results. Within-couple acts of condomless anal intercourse (CLAI) were categorized by strategy: condom-protected, biomedically protected (undetectable VL and/or pre-exposure prophylaxis [PrEP]), or not protected by either (HIV-negative partners engaging in insertive CLAI, receptive CLAI with withdrawal, or receptive CLAI with ejaculation). Results: A total of 343 couples were included in this analysis (153 in Australia, 93 in Brazil and 97 in Thailand). Three-quarters of HIV-positive partners were consistently virally suppressed (<200 copies/mL) during follow-up, and HIV-negative partners had correct perceptions of their partner's VL result for 76.5% of tests. One-third of HIV-negative partners used daily PrEP during follow-up. Over follow-up, 73.8% of couples had CLAI. HIV-negative partners reported 31,532 acts of anal intercourse with their HIV-positive partner. Of these, 46.7% were protected by condoms, 48.6% by a biomedical strategy and 4.7% of acts were not protected by these strategies. Australian couples had fewer condom-protected acts and a higher proportion of biomedically protected acts than Brazilian and Thai couples. Of the 1473 CLAI acts where the perceived VL was detectable/unknown and were not protected by PrEP (4.7% of all acts), two-thirds (n = 983) were when the HIV-negative partner was insertive (strategic positioning). Of the 490 acts when the HIV-negative partner w

Background: Tenofovir disoproxil fumarate (TDF) is widely used in the management of HIV-infection, but has been associated with renal impairment in a small proportion of patients. Tenofovir alafenamide (TAF), a novel prodrug of tenofovir, causes less renal impairment and can improve renal function in patients switched from TDF. The factors which predict improved renal function in patients switching from TDF to TAF have yet to be described. Aim: To determine which patient factors are associated with an improvement in renal function following the switch from a TDF- to a TAF-based HIV antiretroviral regimen. Methods: A retrospective analysis was performed of a cohort from a publicly funded sexual health clinic in Sydney, Australia. All HIV-positive clinic patients switched from a TDF- to TAF-containing regimen between January 2016 and August 2018 were eligible for inclusion. Laboratory results were obtained from patients' electronic medical records. The statistical significance of differences between pre- and post-switch means was determined by paired t-tests, adjusted for baseline values, and associations between continuous variables by univariate linear regression. Results: 79 patients met inclusion criteria. The majority were male (89%), with a median age of 44 years (IQR: 34.5 to 53). Patients had a mean pre-switch estimated glomerular filtration rate (eGFR) of 95 ± 2 mL/min/1.73 m2, and there was no significant change post-switch (p = 0.062). Pre-switch eGFR was a significant predictor of the magnitude of eGFR change after the switch (p < 0.001), but there was no significant association with age (p = 0.189), cumulative TDF exposure (p = 0.454) or baseline urinary protein to creatinine ratio (p = 0.814). Conclusion: While there was no significant difference in mean eGFR, in patients switched from TDF to TAF, baseline eGFR was a significant predictor of the change in eGFR. This suggests that patients on TDF with poorer baseline renal function would benefit more from

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

OBJECTIVES: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). METHODS: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. RESULTS: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. CONCLUSIONS: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.

© 2017 CSIRO. Background: The widespread availability of direct-acting antivirals (DAAs) is expected to drastically improve the treatment uptake and cure rate of hepatitis C virus (HCV). In this paper, rates of and factors associated with HCV treatment uptake and cure in the HIV co-infected population in Australia were assessed before access to DAAs. Methods: The medical records of patients in the Australian HIV Observational Database who were reported to be HCV antibody positive from 1999 to 2014 were reviewed for HCV treatment data. Patients with detectable HCV RNA were included in this analysis. Logistic regression models were applied to identify factors associated with treatment uptake and HCV sustained virological response (SVR) 24 weeks' post treatment. Results: The median follow-up time of those with chronic HCV/HIV co-infection was 103 months (interquartile range 51-166 months). Of 179 HCV viraemic patients, 79 (44.1%) began treatment. In the adjusted model, a higher METAVIR score was the only significant factor associated with treatment uptake (odds ratio (OR) 8.87, 95% confidence interval (CI) 2.00-39.3, P≤0.004). SVR was achieved in 37 (50%) of 74 treated patients. HCV genotypes 2/3 compared with 1/4 remained the only significant factor for SVR in an adjusted multivariable setting (OR 5.44, 95% CI 1.53-19.4, P≤0.009). Conclusions: HCV treatment uptake and SVR have been relatively low in the era of interferon-containing regimens, in Australian HIV/HCV coinfected patients. With new and better tolerated DAAs, treatment of HCV is likely to become more accessible, and identification and treatment of HCV in co-infected patients should become a priority.

Background: Individuals aged 13–24 years undergo vast physical, cognitive, social and psychological changes. Australian data regarding clinical outcomes of those diagnosed with HIV in this age are sparse. Aim: We aimed to describe demographic factors, virologic and clinical outcomes of individuals aged 13–24 years diagnosed with human immunodeficiency virus (HIV). Methods: Patients diagnosed with HIV after 1997 in the Australian HIV Observational Database were divided into young adults, diagnosed at age <25 years (n = 223), and older adults (n = 1957). Demographic and clinical factors were compared between groups. Results: Young adults had a median age at diagnosis of 22 years (inter quartile range (IQR) 20–24) and median age at treatment initiation of 24 years (IQR 22–26). They were more likely to be female than the older cohort (21.1 vs 10.8%; P < 0.001). Men who have sex with men was the most common exposure category in both groups. CD4 count at diagnosis was significantly higher in younger than older adults (median 460 vs 400 cells/mm 3 , P = 0.006), whereas HIV viral load at diagnosis was lower (35 400 vs 61 659 copies/mL, P = 0.011). The rate of loss to follow up (LTFU) was higher in young adults (8.0 vs 4.3 per 100PY, P < 0.001). Young adults were more likely to have a treatment interruption compared to older adults (5.3 vs 4.0 per 100PY, P = 0.039). Rates of treatment switch, time to treatment change, and CD4 and viral load responses to treatment were similar between groups. Conclusions: Young adults were diagnosed with HIV at higher CD4 counts and lower viral loads than their older counterparts. LTFU and treatment interruption were more common highlighting the need for extra efforts directed towards retention in care and education regarding the risks of treatment interruptions.

INTRODUCTION: Men who have sex with men (MSM) living with HIV have a high risk of anal cancer, which is often detected at late stages, when morbidity and mortality are high. The objective of this study was to describe the feasibility and challenges to incorporating regular digital anorectal examination (DARE) into routine HIV care for MSM living with HIV, from the perspective of patients, physicians and the health service. METHODS: In 2014, we recruited 327 MSM living with HIV, aged 35 and above from one major sexual health centre (n = 187), two high HIV caseload general practices (n = 118) and one tertiary hospital (n = 22) in Melbourne, Australia. Men were followed up for two years and DARE was recommended at baseline, year 1 and year 2. Data were collected regarding patient and physician experience, and health service use. An ordered logit model was used to assess the relationship between sociodemographic factors and the number of DAREs performed. RESULTS: Mean age of men was 51 (SD ± 9) years, 69% were Australian born, 32% current smokers, and mean CD4 was 630 (SD ± 265) cells per mm3 , with no significant differences between clinical sites. Overall, 232 (71%) men received all three DAREs, 71 (22%) received two DAREs, and 24 (7%) had one DARE. Adverse outcomes were rarely reported: anal pain (1.2% of total DAREs), bleeding (0.8%) and not feeling in control of their body during the examination (1.6%). Of 862 DAREs performed, 33 (3.8%) examinations resulted in a referral to a colorectal surgeon. One Stage 1 anal cancer was detected. CONCLUSION: Incorporation of an early anal cancer detection programme into routine HIV clinical care for MSM living with HIV showed high patient acceptability, uncommon adverse outcomes and specialist referral patterns similar to other cancer screening programmes.

introduction: The effectiveness of daily pre-exposure prophylaxis (PrEP) is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM). This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project. Materials and methods: Individuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day), event-driven (pills taken only around specific risk events), or periodic (daily dosing during periods of increased risk). results: Overall, 315 GBM (98% of study sample) provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/ vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95% confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76)]. Discussion: Individuals’ preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to study partic

Introduction: The effectiveness of daily pre-exposure prophylaxis (PrEP) is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM). This paper explores preferences for PrEP dosing schedules among GBM at baseline in thePRELUDEdemonstration project. Materials and methods: Individuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day), event-driven (pills taken only around specific risk events), or periodic (daily dosing during periods of increased risk). Results: Overall, 315 GBM (98% of study sample) provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95% confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76)]. Discussion: Individuals' preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to study participa

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59–67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59-67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

OBJECTIVE: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. METHODS: The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status. RESULTS: Anal HPV results from 606 (98.2%) of 617 participants (median age 49 years, 35.7% HIV-positive) showed 525 (86.7%) had ≥1 HPV type and 178 (29.4%) had HPV16. Over one third of participants (214, 35.3%) had no nonavalent vaccine-preventable types detected. Two (0.3%) participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001) and younger participants (p=0.059) were more likely to have more vaccine-preventable HPV types detected. CONCLUSION: Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored.

BACKGROUND: Gonorrhoea is one of the most common sexually transmissible infections in men who have sex with men (MSM). Gonorrhoea rates have increased substantially in recent years. There is concern that increasing gonorrhoea prevalence will increase the likelihood of worsening antibiotic resistance in Neisseria gonorrhoeae. A recent randomised controlled trial (RCT) demonstrated that a single-dose of mouthwash has an inhibitory effect against oropharyngeal gonorrhoea. We are conducting the first RCT to evaluate whether daily use of mouthwash could reduce the risk of acquiring oropharyngeal gonorrhoea. METHODS/DESIGN: The OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study is a double-blind RCT and will be conducted at several sexual health clinics and high caseload General Practice (GP) clinics in Melbourne and Sydney, Australia. A total of 504 MSM attending the participating sites will be recruited. Participants will be randomised to either using 'Study mouthwash A' or 'Study mouthwash B' for 12 weeks. Study mouthwash A was inhibitory against N. gonorrhoeae in vitro, whereas study mouthwash B was not. Participants will be instructed to rinse and gargle the study mouthwash for 60 seconds every day. The primary outcome is the proportion of participants with oropharyngeal gonorrhoea detected by nucleic acid amplification test by 12 weeks. DISCUSSION: The results from this trial may provide a novel way to reduce gonorrhoea prevalence and transmission without the use of antibiotics that may be associated with development of resistance. If shown to be effective, the widespread use of mouthwash will reduce the prevalence of oropharyngeal gonorrhoea, which plays key role in driving the emergence of gonococcal antimicrobial resistance through DNA exchange with oral commensal bacteria. The anticipated net effect will be interruption of onward transmission of N. gonorrhoeae within high density sexual networks within MSM populations. TRIAL REGISTRATION: Australian New Ze

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions among homosexual men in Sydney, Australia, we identified 15 examples of papillary immature metaplasia (PIM) in anal biopsy samples. PIM has previously been described in the cervix, but not in the anal canal. PIM is a form of exophytic low-grade squamous intraepithelial lesion (eLSIL) also known as condyloma. In contrast to the maturing keratinocytes and koilocytosis seen in conventional eLSIL, the slender papillary structures of PIM have a surface population of immature squamous cells. In our anal samples PIM was characterized by close proximity to conventional eLSIL, was negative for p16 INK4A (p16) expression, and revealed the presence of a single low-risk HPV genotype (either 6 or 11) in laser capture microdissected lesions. The clinical significance of recognizing PIM lies in preventing misdiagnosis as high-grade squamous intraepithelial lesion, (the presumed precursor to anal cancer), due to the morphologic immaturity of the cell population. In routine practice, awareness of anal canal PIM and p16 immunostaining will prevent this. Further study of the natural history of anal canal PIM is needed.

Introduction: Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. Methods and analysis: PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants - mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. Ethics and dissemination: The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete.

© 2016 The Author(s).Background: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. Methods: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and v

BACKGROUND: Studies regarding the performance of anal cytology in which both the screening test (cytology) and the diagnostic test (high-resolution anoscopy [HRA]) are performed in all members of a screening population are rare. The authors evaluated the performance of liquid-based anal cytology in a cohort of homosexual men in Sydney, New South Wales, Australia. METHODS: The Study of the Prevention of Anal Cancer (SPANC) is a 3-year prospective study of the natural history of anal human papillomavirus infection in homosexual men aged ≥35 years. At baseline, all participants underwent a liquid-based anal cytology test and HRA at the same clinical visit. Biopsies were obtained for histological assessment if lesions suspicious for human papillomavirus infection were visible during HRA. Using any cytological abnormality as the threshold, the sensitivity, specificity, and positive and negative predictive values were calculated against histologically diagnosed high-grade squamous intraepithelial lesions (HSILs). RESULTS: Among 617 men recruited, the median age was 49 years (range, 35-79 years) and 35.7% were positive for the human immunodeficiency virus. Overall, the sensitivity of cytology was 83.2%, the specificity was 52.6%, the positive predictive value was 45.8%, and the negative predictive value was 86.7%. Specificity improved with increasing age (P for trend =.041). Sensitivity was significantly higher in men with >1 anal octant of biopsy-confirmed HSIL (92.9% vs 77.7%; P =.010), and in those who had ≥10 metaplastic cells present on their cytology slides (87.5% vs 70.2%; P =.007). CONCLUSIONS: Anal cytology was found to have a higher specificity in older men while maintaining sensitivity. Sensitivity was higher among those with more extensive HSILs and men with metaplastic cells present on cytology. Cancer Cytopathol 2016;124:415–24. © 2016 American Cancer Society.

Background: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4+ T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4+ subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV+ subjects on suppressive ART compared to HIV-negative controls (HNC). Methods: Twenty-three HIV+ subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM+ epithelial cells, were accurately enumerated by flow cytometry, using counting beads. Results: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4+ T cell count/106 epithelial cells was 2.4-fold lower in HIV+ subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4+ T cell counts were reduced in HIV+ subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA+ B cell counts at either site between HIV+ subjects and HNC. Further analysis showed no difference in CD4+, Tfh, or IgA+ B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4+ T cells, including CCR5+ cells, CD127+ long-term memory cells, CD103+ tissue-resident cells, or CD161+ cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells. Conclusion: While there were lower absolu

BACKGROUND: Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3) are commonly grouped together as high grade squamous intraepithelial lesions (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of homosexual men. METHODS: At the baseline visit in the Study for the Prevention of Anal Cancer (SPANC), all men completed a questionnaire and underwent anal swabbing for cytology and HPV genotyping, followed by high resolution anoscopy. RESULTS: Composite-HSIL prevalence was 47% and 32% among 220 HIV-positive and 396 HIV-negative men, respectively. HSIL-AIN3 (37.7% versus 24.7%; p<0.001), but not HSIL-AIN2 (9.5% versus 7.6%; p=0.395) was more common in HIV-positive men. Recent receptive anal partners (p-trend=0.045), and increasing number of high-risk (HR)-HPV types (p-trend<0.001) were associated with HSIL-AIN2. Lifetime receptive partners (p-trend<0.001), HIV status (OR 1.74; 95% CI: 1.05-2.87) and HPV16 (OR 3.00; 95% CI: 1.56-5.75) were associated with HSIL-AIN3. HPV16 was the most common HR-HPV type detected in men with HSIL-AIN3, both HIV-negative (61.1%) and HIV-positive (54.9%). HPV16 was less commonly detected in men with HSIL-AIN2. CONCLUSIONS: Grouping HSIL-AIN2 and HSIL-AIN3 as HSIL may mask considerable heterogeneity in anal cancer risk. Given the strong link between HPV16 and anal cancer, men with HSIL-AIN3 and HPV16 are likely to be at greatest risk of cancer.

BACKGROUND: The ThinPrep Imaging System (TIS) is an accurate time-saving method of reading cervical ThinPrep slides in screening programs. As anal and cervical cytology are morphologically similar, TIS can potentially be used for anal cytology. We assessed the performance of TIS on anal ThinPrep slides from homosexual men in a natural history study of human papillomavirus-related anal abnormalities. METHODS: Four hundred nineteen anal cytology slides were processed by TIS and classified by a cytologist as either No further review (slide archived) or Manual review (slide requiring full manual screen). The results were compared with the original manual screening report for all slides and specifically for those screening episodes accompanied by a high-grade squamous intraepithelial lesion (HSIL) on concurrent biopsy. RESULTS: One hundred seventy six of 419 (42.0%) slides were classified as No further review, with a trend of decreasing proportions as the degree of severity of the cytological abnormality increased. Thirteen (27.7%) slides with an original unsatisfactory report were classified as No further review. Eighty two (92.1%) of those with biopsy HSIL and cytological abnormality were classified for Manual review, including all 45 (100%) with cytological HSIL. CONCLUSION: The cervical algorithm of TIS performed best on anal samples when HSIL was present both cytologically and histologically. The 27.7% unsatisfactory slides classified as No further review may indicate need for use of different criteria from cervical cytology. Because of the high prevalence of abnormalities, and hence the large proportion of slides needing manual review, the cytologist time-saving would compare unfavorably with use of TIS in cervical screening.

Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.

Background: There are few data regarding clinical care and outcomes of Indigenous Australians living with HIV and it is unknown if these differ from non-Indigenous HIV-positive Australians. Methods: AHOD commenced enrolment in 1999 and is a prospective cohort of HIV-positive participants attending HIV outpatient services throughout Australia, of which 20 (74 %) sites report Indigenous status. Data were collected up until March 2013 and compared between Indigenous and non-Indigenous participants. Person-year methods were used to compare death rates, rates of loss to follow-up and rates of laboratory testing during follow-up between Indigenous and non-Indigenous participants. Factors associated with time to first combination antiretroviral therapy (cART) regimen change were assessed using Kaplan Meier and Cox Proportional hazards methods. Results: Forty-two of 2197 (1.9 %) participants were Indigenous. Follow-up amongst Indigenous and non-Indigenous participants was 332 & 16270 person-years, respectively. HIV virological suppression was achieved in similar proportions of Indigenous and non-Indigenous participants 2 years after initiation of cART (81.0 % vs 76.5 %, p = 0.635). Indigenous status was not independently associated with shorter time to change from first- to second-line cART (aHR 0.95, 95 % CI 0.51-1.76, p = 0.957). Compared with non-Indigenous participants, Indigenous participants had significantly less frequent laboratory monitoring of CD4 count (rate:2.76 tests/year vs 2.97 tests/year, p = 0.025) and HIV viral load (rate:2.53 tests/year vs 2.93 tests/year, p < 0.001), while testing rates for lipids and blood glucose were almost half that of non-indigenous participants (rate:0.43/year vs 0.71 tests/year, p < 0.001). Loss to follow-up (23.8 % vs 29.8 %, p = 0.496) and death (2.4 % vs 7.1 %, p = 0.361) occurred in similar proportions of indigenous and non-Indigenous participants, respectively, although causes of death in both groups were mostly non-HIV-relat

Introduction: Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, highgrade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. Methods and analysis: HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and followup biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as nonpersistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. Ethics and dissemination: The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to parti

In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions, we examined the reproducibility of histological high-grade squamous intraepithelial lesion (HSIL). Three expert anogenital pathologists share the reporting of histological specimens from the Study of the Prevention of Anal Cancer (SPANC), utilising Lower Anogenital Squamous Terminology (LAST) criteria. In total, 194 previously reported biopsies were randomly chosen within diagnostic strata [50 HSIL–anal intraepithelial neo-plasia (AIN) 3; 45 HSIL–AIN 2; 49 ‘flat’ low-grade squamous intraepithelial lesion (LSIL); 50 ‘exophytic’ LSIL; and 50 negative for squamous intraepithelial lesion] and reviewed by each of these three pathologists. Consensus was defined as agreement between at least two review diagnoses, using a binary classification of HSIL and non-HSIL, or if consensus was not obtained in this way, it was achieved through a multiheader microscope session by the three pathologists. We found very high agreement between original and consensus diagnoses (Kappa = 0.886) and between each pathologist's review and consensus (Kappas = 0.926, 0.917 and 0.905). Intra-observer agreement for the three pathologists was 0.705, 1.000 and 0.854. This high level of diagnostic reproducibility indicates that the findings of SPANC should be robust and provide reliable information about HPV-related anal canal disease.

Background: Condomless anal intercourse (CLAI) has long been recognized as the primary mode of sexual transmission of HIV in gay and other men who have sex with men (MSM). A variety of measures of CLAI have been commonly used in behavioral surveillance for HIV risk and to forecast trends in HIV infection. However, gay and other MSM's sexual practices changed as the understanding of disease and treatment options advance. In the present paper, we argue that summary measures such as "any CLAI" do not accurately measure HIV sexual risk behavior. Methods: Participants were 1,427 HIV-negative men from the Health in Men cohort study run from 2001 to 2007 in Sydney, Australia, with six-monthly interviews. At each interview, detailed quantitative data on the number of episodes of insertive and receptive CLAI in the last 6 months were collected, separated by partner type (regular vs. casual) and partners' HIV status (negative, positive, and HIV status unknown). Results: A total of 228,064 episodes of CLAI were reported during the study period with a mean of 44 episodes per year per participant (median: 14). The great majority of CLAI episodes were with a regular partner (92.6%), most of them with HIV-negative regular partners (84.8%). Participants were more likely to engage in insertive CLAI with casual than with regular partners (66.7 vs. 55.3% of all acts of CLAI with each partner type, p < 0.001). Men were more likely to report CLAI in the receptive position with HIV-negative and HIV status unknown partners than with HIV-positive partners (p < 0.001 for both regular and casual partners). Conclusion: Gay and other MSM engaging in CLAI demonstrate clear patterns of HIV risk reduction behavior. As HIV prevention enters the era of antiretroviral-based biomedical approach, using all forms of CLAI indiscriminately as a measure of HIV behavioral risk is not helpful in understanding the current drivers of HIV transmission in the community.

INTRODUCTION: Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. METHODS AND ANALYSIS: HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. ETHICS AND DISSEMINATION: The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to pa