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Background: Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP., Methods: Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790., Findings: Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44)., Interpretation: HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk., Funding: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences., Competing Interests: Declaration of interests AEG received a grant from the NSW Ministry of Health and the ACT Health Directorate, and non-financial support from Gilead Sciences, enabling the conduct of the reported study. AEG also receives personal fees from Viiv Healthcare and a grant from Seqirus Australia, outside the submitted work. AC reports grants, personal fees, and non-financial support from Gilead Sciences, grants and personal fees from ViiV Healthcare, and grants and personal fees from MSD, outside the submitted work. BY reports travel and accommodation support from Mylan Australia to present at the HIV Clinical Care meeting in the ACT in 2019, unrelated to the submitted work. BRB reports personal fees from Gilead Sciences, outside the submitted work. CTMS reports support from Gilead Sciences to attend a workshop and accommodation. DAB reports grants from ViiV Healthcare, Gilead Sciences, and MSD, during the conduct of the study. MB reports grants from NSW State Government during the conduct of the study; grants and personal fees from Gilead Sciences, ViiV Healthcare, and AbbVie, personal fees from Janssen, and grants from MSD and GSK, outside the submitted work. NJD reports grants from Gilead Sciences unrelated to the submitted work. PR reports institutional research funding and speaking honoraria received from Gilead Sciences unrelated to this manuscript. SM reports grants from ACT Health Directorate and ACT Government, during the conduct of the study. All other authors report no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Human papillomavirus (HPV) causes anal warts and anal squamous cell carcinoma (SCC). A higher incidence of anal cancer has been found among individuals previously diagnosed with anogenital warts. We aimed to investigate the association between anal warts and the presumed anal SCC precursor high-grade squamous intraepithelial lesion (HSIL), among participants in the Study of the Prevention of Anal Cancer (SPANC). SPANC was a longitudinal study of anal HPV infections and related lesions among gay and bisexual men (GBM) age 35 years and older, in Sydney, Australia. Anal cytology and high-resolution anoscopy were performed. Logistic regression was used to investigate the association between clinically diagnosed anal warts and intra-anal composite-HSIL (cytology and/or histology) at the baseline visit. The prevalence of HSIL within biopsies from intra-anal warts was calculated. Laser capture microdissection (LCM) and HPV-genotyping was performed on HSIL lesions. Among 616 participants at study entry, 165 (26.8%) and 51 (8.3%) had intra-anal and perianal warts, respectively. Warts were associated with composite-HSIL, even after adjustment for HIV status, age, lifetime receptive anal intercourse partner number, and smoking (perianal: aOR 2.13, 95% CI 1.17-3.87, p  = 0.013; intra-anal: aOR 1.69, 95% CI 1.16-2.46, p  = 0.006). HSIL was detected in 24 (14.5%) of 165 biopsies from intra-anal warts. Of 17 HSIL lesions, 16 (94.1%) had high-risk HPV detected by LCM. Anal warts were common. Prevalent anal warts were associated with composite-HSIL. HSIL may be detected within biopsies of intra-anal warts. Anal warts may be a useful addition to risk stratification for HSIL among GBM.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Sexually transmitted infection (STI) notifications are increasing among older individuals. Many older gay and bisexual men (GBM) are sexually active and have multiple partners. We aimed to investigate the prevalence, incidence and predictors of anal chlamydia, anal gonorrhoea and syphilis in older GBM., Methods: The Study for the Prevention of Anal Cancer (SPANC) was a prospective cohort study of HPV infections and related anal lesions among community-recruited GBM age ≥ 35 years in Sydney, Australia. At baseline and subsequent annual visits, recent STI diagnoses were collected via questionnaire ('interval diagnoses') and STI testing occurred ('study visit diagnoses'). Baseline STI prevalence was calculated using study visit diagnoses. Incidence of anal chlamydia and gonorrhoea was calculated using interval and study visit diagnoses. Syphilis incidence was calculated using interval diagnoses. Univariate and multivariate analysis using Cox proportional hazards were undertaken to investigate the association between risk factors and incident STI., Results: Among 617 GBM, the median age was 49 years (range 35-79) and 35.8% (n=221) were HIV-positive. At baseline, STI prevalence was: anal chlamydia 2.3% (n=14); anal gonorrhoea 0.5% (n=3) and syphilis 1.0% (n=6). During 1428 person-years of follow-up (PYFU), the incidence (per 100 PYFU) of anal chlamydia, anal gonorrhoea and syphilis was 10.40 (95% CI 8.82 to 12.25), 9.11 (95% CI 7.64 to 10.85) and 5.47 (95% CI 4.38 to 6.84), respectively. In multivariate analysis, HIV-positivity, higher number of recent condomless receptive anal intercourse partners and baseline methamphetamine use were associated with each STI. Sex with 'fuck-buddies' was associated with anal chlamydia and gonorrhoea. Age was not associated with any STI., Discussion: There was a high incidence of STI among SPANC participants. Age should not be used as a proxy for sexual risk and older GBM require a detailed sexual behaviour and recreational drug use history. Interventions that specifically target STI risk among older GBM should be considered., Competing Interests: Competing interests: AEG has received honoraria and research funding from CSL Biotherapies, honoraria and travel funding from Merck. CKF has received honoraria, travel funding and research funding from CSL and Merck, and owns shares in CSL Biotherapies. SMG has received advisory board fees and grant support from CSL and GlaxoSmithKline, and lecture fees from Merck, GlaxoSmithKline and Sanofi Pasteur; in addition, has received funding through her institution to conduct clinical HPV vaccine studies for MSD and GlaxoSmithKline and is a member of the Merck Global Advisory Board as well as the Merck Scientific Advisory Committee for HPV. RJH has received support from CSL Biotherapies and MSD., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Asian men who have sex with men (MSM) who have recently arrived in Australia are an emergent risk group for HIV; however, little is known about how they compare to Australian MSM diagnosed with HIV. This study compared the characteristics of these two groups., Methods: A retrospective, cross-sectional study of MSM diagnosed with HIV between January 2014 and October 2017 in Melbourne and Sydney public sexual health clinics. Asian MSM were those who had arrived in Australia within 4 years of diagnosis., Results: Among 111 Asian men, 75% spoke a language other than English, 88% did not have Medicare and 61% were international students. Compared with Australian men (n=209), Asian men reported fewer male sexual partners within 12 months (median 4 versus 10, p<0.001), were less likely to have tested for HIV previously (71% versus 89%, p<0.001) and had a lower median CD4 count (326 versus 520, p<0.001). Among Asian men, HIV subtype CRF01-AE was more common (55% versus 16%, p<0.001) and subtype B less common (29% versus 73%, p<0.001)., Conclusions: Asian MSM diagnosed with HIV reported lower risk and had more advanced HIV. Implications for public health: HIV testing and preventative interventions supporting international students are required., (© 2019 The Authors.)

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 28 696 individuals, a total of 129 cases of ASCC were identified. The crude incidence was 36.3 per 100 000 person-years and it increased sharply from 14.8 to 62.1 per 100 000 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.

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.

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 participants. Further research investigating how behaviours and PrEP preferences change correspondingly over time is needed., Trial Registration: ClinicalTrials.gov NCT02206555. Registered 28 July 2014.

Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia., Design: Baseline analysis of a 3-year cohort study., Methods: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers., Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005)., Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

Anal cytology has been suggested as a screening test for the anal cancer precursor high-grade squamous intraepithelial lesion (HSIL). We aimed to assess the prevalence and predictors of initial unsatisfactory anal cytology tests ('unsats'). The Study of the Prevention of Anal Cancer is a natural history study of anal human papillomavirus (HPV) and precancerous lesions among gay and bisexual men (GBM) of at least 35 years in Sydney, Australia. At each study visit, an anal swab is collected for cytological testing. Unsats are defined as slides with fewer than 2000 nucleated squamous cells and no abnormal cells. Among 617 GBM enrolled, the median age was 49 (range: 35-79) years and 220 (35.7%) were HIV positive. Initial unsats occurred in 61 (9.9%, 95% confidence interval: 7.6-12.5%), and 29 (4.7%, 95% confidence interval: 3.2-6.7%) remained unsatisfactory on repeat cytology. Initial unsats were associated with fewer lifetime anal-receptive partners with a condom (P=0.007); fewer recent anal-receptive sexual partners without a condom (P=0.005); never having had anal chlamydia (P=0.023) or gonorrhea (P=0.003); HIV-negative status (P=0.002); fewer total (P=0.002), low-risk (P=0.005), and high-risk (P=0.015) HPV types detected; lack of anal HPV18 detection (P=0.001); never having anally douched (P<0.001); and douching with soapy water (P=0.009) among those who douched. Unsats were less common among those with histologic HSIL (P=0.008) and nonsignificantly less common among those with fewer anal canal octants affected by HSIL (P=0.080), but were more common among those who felt more nervous (P=0.020) during the examination. Our findings suggest that unsats are more common among GBM with less receptive anal sexual experience. Avoiding douching with soapy water and strategies to aid patient relaxation during sampling may reduce the unsat rate.

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/10 6 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 absolute CD4 + counts in the TI and LC in HIV + subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA + B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.

Objectives: To investigate an increase in lymphogranuloma venereum (LGV) notifications in New South Wales (NSW)., Methods: Enhanced surveillance of notified LGV cases in NSW between May 2010 and April 2012 using doctor and patient questionnaires., Results: Thirty-seven doctors who had diagnosed 67 (76%) of 88 notified anorectal LGV infections were interviewed. The majority (n=33, 89%) of treating doctors were formally trained and accredited in HIV management and prescribing, and most (n=32, 86%) worked in a public sexual health clinic or a general practice with a high caseload of men who have sex with men (MSM). All 67 cases were MSM who resided in inner-city Sydney and all were serovar L2b. Anal symptoms had been present in 64 cases (96%, 95%CI 87-99%) for a median of 8 days (range 2-1,825) prior to presentation. Almost one-third (n=20) had another concurrent STI diagnosed. Most (82%) of the 22 interviewed patients reported being HIV positive and having other STIs diagnosed over the past year. In the preceding month, all 22 men reported condomless anal sex and the median number of casual sexual partners was 5 (range 0-100)., Conclusions: Characteristics of LGV cases in NSW are similar to those described worldwide, suggesting that a sexually adventurous subgroup of MSM are at particular risk of infection., Implications: Education of non-sexual-health clinicians on LGV risk factors, presentation, testing and management may allow more timely diagnosis and notification of contacts to reduce LGV transmission in the community., (© 2016 Public Health Association of Australia.)

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 neoplasia (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.

Reducing viral-load measurements to annual testing in virologically suppressed patients increases the estimated mean time those patients remain on a failing regimen by 6 months. This translates to an increase in the proportion of patients with at least one Thymidine Analogue Mutation from 10% to 32% over one year.

Background: Non-occupational HIV post-exposure prophylaxis (NPEP) is prescribed following a risk exposure in an effort to reduce the risk of HIV seroconversion. We aimed to describe the prescribing practices of NPEP at RPA Sexual Health in Sydney, the prevalence and correlates of adverse events (AEs), and factors associated with completing the 28-day course., Methods: The study population included individuals prescribed NPEP during January 2008-December 2011. Correlates of AEs and course completion were assessed by logistic regression., Results: On 319 occasions during the study period, 282 individuals presented for NPEP. Over 90% of presentations followed unprotected anal intercourse between men, mostly receptive (63.6%). Tenofovir-emtricitabine-stavudine (n=149; 46.7%) and tenofovir-emtricitabine (n=136; 42.6%) were most commonly prescribed. AEs were reported at 101 presentations (31.7%, 95% confidence interval (CI): 26.6-37.1%), with nausea and lethargy/malaise being the most common. Younger age (P for trend=0.032), earlier year of NPEP prescription (P for trend=0.011), being prescribed a regimen other than tenofovir-emtricitabine (P=0.026), changing the NPEP regimen (P<0.001) and known completion of the course (P=0.005) were independently associated with AEs. The course was completed in 228 presentations (71.5%, 95% CI: 66.2-76.4%). Completion was associated with reporting AEs (P=0.007) and changing regimen (P=0.001). No documented NPEP failures were identified, although two recipients subsequently seroconverted to HIV due to ongoing high-risk behaviour., Conclusions: NPEP is appropriately targeted to the highest risk HIV exposures at our clinic. Active recall may improve follow-up rates in NPEP recipients.

Background: Human papillomavirus 16 (HPV16) has been causally associated with approximately 70% of anal cancers. This cancer is markedly increasing among homosexual men. There is limited knowledge of the epidemiology and natural history of anal HPV infection in homosexual men., Methods: Behavioral data and sera for antibodies to HPV16 L1 were collected annually for 1427 HIV-negative and 245 HIV-positive Australian homosexual men. Seroprevalence, seroincidence, and risk factors were calculated., Results: Among HIV-negative men, 25.4% were HPV16 seropositive at baseline compared with 44.3% of HIV-positive men. HPV16 seroincidence was 3.1/100 person-years among HIV-negative men and 1.3/100 person-years among HIV-positive men. Seroincidence among HIV-negative men remained >3% per year until 45 years of age, before declining. In multivariate analyses of data from HIV-negative men, seroprevalent HPV16 was associated with sexual risk behaviors and seropositivity for several viral sexually transmissible infections. Seroincident HPV16 was associated with younger age and unprotected anal intercourse with HIV-positive partners. Among men who predominantly practiced insertive anal intercourse, circumcision was associated with a 57% reduction in seroincident HPV16 (hazard ratio = 0.43, 95% confidence interval: 0.21-0.88, P = 0.021)., Conclusions: HPV16 seroincidence remained common in men until their mid 40s suggesting that vaccination may be protective in sexually active young gay men. Both HPV16 seroprevalence and seroincidence correlated well with markers of higher risk sexual activity, particularly receptive anal sexual practices. An association between circumcision and decreased HPV16 seroconversion in HIV-negative men who preferred the insertive position in anal sex was observed.

There is limited published research on sexually transmissible infections (STI) among aging HIV populations. The available literature on sexual behaviour and STI among older people with HIV is reviewed here and contrasted with data from older individuals in the general population and from older populations at high risk of HIV. A sizeable minority of older people with HIV continue to engage in higher risk sexual behaviour and thus remain at high risk of STI. There is no clear evidence of a consistent effect of older age on STI rates, clinical presentation or clinical course among HIV-infected populations, although gay men with HIV aged in their 40s or older seem to be at higher risk than younger men of acquiring several STI, including syphilis and lymphogranuloma venereum. STI risks in older people living with HIV need to be regularly assessed. Higher risk sexual behaviour and disproportionately higher rates of STI indicate that regardless of age, a thorough STI assessment should be regularly undertaken for all HIV-positive gay men as part of their routine HIV care.

The significance of interethnic variation in CD4 counts between Asian and Caucasian populations is not known. Patients on combination antiretroviral therapy from Treat Asia and Australian HIV Observational Databases (TAHOD, predominantly Asian, n = 3356; and AHOD, predominantly Caucasian, n = 2312, respectively) were followed for 23 144 person-years for AIDS/death and all-cause mortality endpoints. We calculated incidence-rates and used adjusted Cox regression to test for the interaction between cohort (TAHOD/AHOD) and time-updated CD4 count category (lagged by 3 months) for each of the endpoints. There were 382 AIDS/death events in TAHOD (rate: 4.06, 95%CI: 3.68-4.50) and 305 in AHOD (rate: 2.39, 95%CI: 2.13-2.67), per 100 person-years. At any given CD4 count category, the incidence-rates of endpoints were found to be similar between TAHOD and AHOD (in the adjusted models, P > .05 for the interaction term between cohort type and latest CD4 counts). At any given CD4 count, risk of AIDS or death was not found to vary by ethnicity, suggesting that the CD4 count thresholds for predicting outcomes defined in Caucasian populations may be equally valid in Asian populations.

Background: Men who have sex with men (MSM) are disproportionately affected by HIV. The proven efficacy of circumcision in reducing the risk of HIV acquisition among African heterosexual males has raised the question of whether this protective effect may extend to MSM populations. We examined the potential impact of circumcision on an HIV epidemic within a population of MSM., Methods: A mathematical model was developed to simulate HIV transmission in an MSM population. The model incorporated both circumcision and seropositioning, and was used to predict the reduction in HIV prevalence and incidence as a result of the two interventions. Estimates for the time required to achieve these gains were also calculated., Results: We derive simple formulae for the decrease in HIV prevalence with increased circumcision. Our model predicts that if an initially uncircumcised MSM population in a developed country with a baseline HIV prevalence of 10% underwent universal circumcision, HIV incidence would only be reduced to 95% of pre-intervention levels and HIV prevalence to 9.6% after 20 years. In the longer term, our model predicts that prevalence would only decrease from 10% to 6%, but this would take several generations to achieve. The effectiveness of circumcision increases marginally with higher degrees of seropositioning., Conclusions: The results of these calculations suggest that circumcision as a public health intervention will not produce a substantial decrease in HIV prevalence or incidence among MSM in the near future, and only modest reductions are achievable in the long-term.

Introduction: In Australia, Aboriginal youth are disproportionately represented in juvenile detention centres. We assessed the prevalence of sexually transmissible infections (STIs) and blood-borne viruses (BBVs) identified by an Aboriginal Health Worker (AHW)-led screening program delivered to male detainees of a rural juvenile detention centre., Methods: A retrospective review of first screening visit data was performed. Demographic and behavioural data were collected and the prevalence of STI/BBV was assessed., Results: Over a 4-year period to November 2004, 101 screens on new medium-to-long-term detainees were performed. The median age of participants was 17 years (range 14-20) and 87% were Aboriginal. Most reported multiple lifetime sexual partners (mean 14, range 0-60) and a minority had used a condom for the last episode of vaginal intercourse. Injecting drug use and non-professional tattoos or piercings were both reported by over one-third of participants, with over 80% reporting previous incarceration. One-quarter of those screened were newly diagnosed with one or more STI/BBV. The most common infection identified was urethral chlamydia (prevalence 16.3%, 95% confidence interval 10.0-25.5%), although the prevalence of newly diagnosed syphilis, hepatitis B and hepatitis C were each over 5%. Many participants remained susceptible to hepatitis B., Conclusion: An AHW-led STI/BBV screening program identified a large number of asymptomatic and previously undiagnosed infections in this group of young male detainees. Such an education and screening program using skilled Aboriginal staff not affiliated with the correctional system could have a substantial impact on the prevalence of STI/BBV among juvenile detainees.

Background: Ensuring patients receive post-test discussion when collecting HIV test results is an integral component of the HIV testing process. New South Wales Health Department (NSW Health) policy recommends that all patients be given their HIV results in person. We assessed the number of patients who returned for HIV test results to Royal Prince Alfred Sexual Health Clinic in Sydney, Australia, and predictors of return., Methods: The files of 218 patients having consecutive HIV tests from the beginning of January to the end of April 2007 were manually reviewed. Non-consenting patients and those returning to the clinic for another reason were excluded. Multivariate logistic regression was used to determine factors associated with return for HIV results in person within 4 weeks of having the test., Results: Seventy-two of 159 patients (45%) returned for their HIV result within 4 weeks of testing. Independent predictors of return were male gender (P = 0.041), attending the outreach men-only (v. base) clinic (P = 0.017), first HIV test at the clinic (P = 0.002) and sex overseas in the past year (P = 0.048)., Conclusion: Over one-half of patients did not collect their HIV results in person and thus did not receive any post-test discussion. The strongest predictor of return for HIV test results was having a first HIV test at the clinic. Current NSW Health policy is failing to achieve high levels of HIV post-test discussion. For many patients, giving results by telephone may be a more appropriate strategy to ensure HIV post-test discussion.

Background: Circumcision status was examined as an independent risk factor for sexually transmissible infections (STIs) in the Health in Men cohort of homosexual men in Sydney., Methods: From 2001 through 2004, 1427 initially human immunodeficiency virus (HIV)-negative men were enrolled and followed up until mid-2007. All participants were offered annual STI testing. The history of STIs was collected at baseline, and information on sexual risk behaviors was collected every 6 months. At annual face-to-face visits, participants reported STI diagnoses received during the previous year., Results: Circumcision was not associated with prevalent or incident herpes simplex virus 1, herpes simplex virus 2, or self-reported genital warts. There was also no independent association of circumcision with incident urethral gonorrhea or chlamydia. Being circumcised was associated with a significantly reduced risk of incident (hazard ratio, 0.35 [95% confidence interval, 0.15-0.84]) but not prevalent (odds ratio, 0.71 [95% confidence interval, 0.35-1.44]) syphilis. The association was somewhat stronger among men who reported predominantly insertive unprotected anal intercourse (hazard ratio, 0.10 [95% confidence interval, 0.01-0.82])., Conclusions: These are the first prospective data obtained from homosexual men to assess circumcision status as a risk factor for STIs. Circumcised men were at reduced risk of incident syphilis but no other prevalent or incident STIs. Circumcision is unlikely to have a substantial public health impact in reducing acquisition of most STIs in homosexual men.

Background: Syphilis has re-emerged and become established in gay communities in most developed countries since the late 1990s. HIV infected men have been disproportionately affected by this endemic, but it is unclear whether this is due to behavioural or biological reasons. We report incidence and risk factors for syphilis in two community-based cohorts of HIV-negative and HIV-positive homosexual men in Sydney, Australia., Methods: Participants were recruited using similar community-based strategies in both cohorts and underwent annual face-to-face interviews. Syphilis screening was offered to all consenting participants at annual visits., Results: In the HIV-negative cohort, 21 men seroconverted to syphilis and one man had a syphilis re-infection during 2001-07, an incidence of 0.49 per 100 person-years (95% CI: 0.31-0.74). In the HIV-positive cohort during 2005-07, eight men seroconverted and one man had a syphilis re-infection, giving an incidence of 3.62 per 100 person-years (95% CI: 1.67-6.48). All nine reported a recent CD4 count of more than 350 cells microL(-1). Syphilis incidence was significantly higher in the HIV-positive cohort after adjustment for age (hazard ratio (HR) = 9.20, 95% CI: 3.63-23.31). Unprotected anal intercourse (UAI) with HIV-positive partners was significantly associated with incident syphilis in both cohorts (HR = 4.45, 95% CI: 1.37-14.45 in HIV-negative; HR = 8.67, 95% CI: 1.03-72.76 in HIV-positive)., Conclusion: Syphilis incidence was almost 10-fold higher in HIV-positive than in HIV-negative homosexual men, and it was not related to a CD4 count below 350 microL(-1). UAI with HIV positive partners was of particular importance in the transmission of syphilis.

Objective: The objective of this study was to determine the prevalence, incidence, and risk factors for genital and anal warts in HIV-negative homosexual men in Sydney., Study Design: The authors conducted a prospective cohort study. Participants were asked whether they had had genital and anal warts at each interview. Details of lifetime sexual contacts and sexual behaviors in the last 6 months were collected., Results: Among 1,427 men recruited, 8.9% and 19.6% reported a history of genital and anal warts at baseline, respectively. Incidence rates for genital and anal warts were 0.94 and 1.92 per 100 person-years, respectively. In multivariate analysis, both incident genital and anal warts were associated with younger age. In addition, incident genital warts was associated with insertive fingering (P trend = 0.018), whereas incident anal warts was associated with insertive fingering (P trend = 0.007) and insertive fisting (P trend = 0.039)., Conclusions: Anal warts were twice as common as genital warts. Fingering and other manual sexual practices may be an important transmission route for both.

Background: Despite increasing reports of herpes simplex virus (HSV) type 1 (HSV-1)-associated anogenital herpes, there are very limited data comparing the seroepidemiological profile of and risk factors for HSV-1 and HSV type 2 (HSV-2) infection., Methods: Sexual behaviors were examined as risk factors for prevalent and incident HSV-1 and HSV-2 infections in a community-based cohort of 1,427 HIV-negative gay men in Australia., Results: The prevalence of HSV-1 and HSV-2 at baseline was 75% and 23%, respectively. The rate of prevalent infection with HSV-1, as well as the rate of prevalent infection with HSV-2, was much lower in individuals <25 years of age, and each type of infection was associated with a higher number of both male and female sex partners. The median duration of follow-up of the cohort was 2.0 years. Among participants who were susceptible to infection, the incidence rates for HSV-1 and HSV-2 infection were 5.58 and 1.45 cases per 100 person-years, respectively. In multivariate analysis, incident infection with HSV-1 was significantly associated with younger age (P=.027) and reports of frequent insertive oral sex with casual partners (hazard ratio, 3.91 [95% confidence interval, 1.23-12.44]; P=.021). Incident infection with HSV-2 was significantly associated with a variety of anal sex practices with casual partners., Conclusions: Both HSV-1 and HSV-2 were commonly sexually transmitted, and there were more HSV-1 than HSV-2 seroconversions. Public-health strategies targeted against anogenital herpes increasingly need to take into account the importance of HSV-1 infection.