Concurrent nonavalent human papillomavirus (HPV) vaccination and immune stimulation with imiquimod to treat recalcitrant HPV-associated high grade vaginal intra-epithelial neoplasia.

This is the first report describing detailed T cell responses to viral-like proteins contained in an HPV specific vaccine given in combination with Imiquimod for treatment of persistent VAIN2/3. We postulate that stimulation of the innate immune system with Imiquimod and the specific CD4 and CD8T cell responses following HPV vaccination with Gardasil9@ combined to induce clinical remission in a woman with treatment-refractory disease.

Prevalence and associations of larger burden of intra-anal high-grade squamous intraepithelial lesions at baseline in an Australian cohort of gay and bisexual men: The Study of the Prevention of Anal Cancer.

OBJECTIVES: To investigate factors associated with larger burden of intra-anal high-grade squamous intraepithelial lesions (HSIL) in a natural history study of HSIL. METHODS: 617 gay and bisexual men (GBM) attended a baseline visit. High-resolution anoscopy-directed biopsy was performed of suspected HSIL. GBM with biopsy-confirmed HSIL (bHSIL) affecting a single-octant were compared with those who had bHSIL affecting a larger area. RESULTS: Of 196 men with bHSIL at baseline, 73 (37.2 %) had larger bHSIL burden. Larger burden was independently associated with anal HPV16 detection (aOR 2.06, 95 % CI 1.09-3.89, p = 0.026) and infection with a greater number of high-risk HPV types (aOR per type increase 1.25, 95 % CI 1.05-1.49, p-trend = 0.010). CONCLUSION: The observation that men with a larger burden of HSIL also had more risk factors for anal cancer suggests this group may warrant closer observation to ensure earlier detection, and thus improved prognosis, of individuals whose HSIL may progress to anal cancer.

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC).

BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.

Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE.

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. TRIAL REGISTRATION NUMBER: NCT02206555; Pre-results.

Hospitalisation rates and associated factors in community-based cohorts of HIV-infected and -uninfected gay and bisexual men.

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

Timing and frequency of chlamydia and gonorrhoea testing in a cross-sectional study of HIV postexposure prophylaxis recipients.

OBJECTIVES: Australian HIV postexposure prophylaxis (PEP) guidelines recommend Chlamydia trachomatis (CT) and Neisseria gonorrheae (NG) testing at both baseline and 2-week postexposure visits. We aimed to determine the diagnostic yield of testing at one or more visits, and predictors of infection. METHODS: Data were collected from patients prescribed PEP at RPA Sexual Health over a 4-year period from January 2008 to December 2011. Predictors of CT/NG were assessed by logistic regression. RESULTS: 282 individuals presented for PEP on 319 occasions during the study period. The majority (94.3%) were male and over 90% of presentations followed unprotected anal sexual exposures. Most (279, 87.5%) had CT/NG testing at least once. Almost half (153, 48.0%) of baseline presentations, two-thirds (214, 67.1%) of 2-week presentations and over a quarter (88, 27.6%) of both presentations included CT/NG testing. CT/NG was diagnosed at baseline in eight (5.2%, 95% CI 2.3% to 10.0%) presentations. A new CT/NG diagnosis occurred at the 2-week visit in 18 (8.4%, 95% CI 5.1% to 13.0%) presentations, of whom 7 tested negative and 11 were not tested at baseline. Over one-quarter (28.1%) of PEP recipients reported sexual contact between baseline and 2-week visits. Independent predictors of CT/NG at baseline were recent sex work (OR 48.0, 95% CI 3.77 to 611.94); and at 2 weeks a known HIV-positive PEP exposure source (OR 3.54, 95% CI 1.04 to 12.06) and sex between baseline and 2-week visits (OR 3.63, 95% CI 1.10 to 11.96). CONCLUSIONS: Our findings suggest that screening PEP recipients for CT/NG at both baseline and 2 weeks may be warranted.

Defining high HIV incidence subgroups of Australian homosexual men: implications for conducting HIV prevention trials in low HIV prevalence settings.

OBJECTIVES: The aim of the study was to assess whether subpopulations with sufficiently high HIV incidences for HIV prevention trials can be identified in low HIV incidence settings such as Australia. METHODS: In a community-based cohort study of HIV-negative homosexually active men in Sydney, Australia, potential risk factors associated with an annual HIV incidence of ≥2 per 100 person-years (PY) were identified. A stepwise procedure ranked these factors according to HIV incidence, to create a 'high-incidence' subgroup of participants. Willingness to participate in HIV prevention trials was assessed. RESULTS: Although the incidence in the cohort overall was only 0.78 per 100 PY, nine risk variables were associated with an HIV incidence of 2 per 100 PY or greater. Stepwise inclusion of these variables revealed a 'high-incidence' subgroup of men representing 24% of the total follow-up time with a combined HIV incidence of 2.71 per 100 PY, who reported at least one of three risk factors in the past 6 months. These men were more willing than others to participate in vaccine and antiretroviral therapy HIV prevention trials. CONCLUSIONS: These findings demonstrate that it is possible to identify high HIV incidence subpopulations in low-incidence settings such as Australia, and these men are of above average willingness to participate in HIV prevention trials.

Attitudes towards new HIV biomedical prevention technologies among a cohort of HIV-negative gay men in Sydney, Australia.

OBJECTIVES: The aim of the study was to explore the awareness of rectal microbicides, the use of pre-exposure prophylaxis (PREP) and the willingness to participate in biomedical HIV prevention trials in a cohort of HIV-negative gay men. METHODS: In a community-based cohort study, HIV-negative homosexually active men in Sydney, Australia were questioned about awareness of rectal microbicides, use of PREP, and willingness to participate in trials of such products. Predictors of awareness and willingness to participate were analysed by logistic regression. Use of PREP was examined prospectively. RESULTS: Overall, 14% had heard of rectal microbicides. Older (P=0.05) and university-educated men (P=0.001) were more likely to have knowledge of rectal microbicides. Almost one-quarter (24%) of men reported that they were likely/very likely to participate in rectal microbicide trials. Among those men with definite opinions on participation, awareness of rectal microbicides was significantly associated with unwillingness to participate [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.65-0.93, P=0.007]. Willingness to participate in trials using antiretroviral drugs (ARVs) to prevent HIV infection was reported by 43% of men, and was higher among those who reported unprotected anal intercourse (UAI) with HIV-positive partners (OR 1.88, 95% CI 0.99-3.56). There was no evidence of current PREP use. CONCLUSIONS: This study demonstrates that Australian gay men have had little experience with PREP use and rectal microbicides. About half would be willing to consider participation in trials using ARVs to prevent HIV infection. Extensive community education and consultation would be required before PREP or rectal microbicides could be trialled in populations of gay Australian men.

Cost-effectiveness of HIV nonoccupational post-exposure prophylaxis in Australia.

OBJECTIVE: The aim of the study was to determine the cost-effectiveness of HIV nonoccupational post-exposure prophylaxis (NPEP) in Australia. METHODS: A retrospective cost analysis of a population-based observational cohort of 1601 participants eligible for NPEP in Australia between 1998 and 2004 was carried out. We modelled NPEP treatment costs and combined them with effectiveness outcomes to calculate the cost per seroconversion avoided. We estimated the cost-utility of the programme, and sensitivity and threshold analysis was performed on key variables. RESULTS: The average NPEP cost per patient was A$1616, of which A$848 (52%) was for drugs, A$331 (21%) for consultations, A$225 (14%) for pathology and A$212 (13%) for other costs. The cost per seroconversion avoided in the cohort was A$1 647,476 in our base case analysis, and A$512,410 when transmission rates were set at their maximal values. The cost per quality-adjusted life-year (QALY) was between A$40,673 and A$176,772, depending on the risks of HIV transmission assumed. CONCLUSIONS: In our base case, NPEP was not a cost-effective intervention compared with the widely accepted Australian threshold of A$50,000 per QALY. It was only cost-effective after receptive unprotected anal intercourse exposure to an HIV-positive source. Although NPEP was a relatively well-targeted intervention in Australia, its cost-effectiveness could be improved by further targeting high-risk exposures.

The public health impact of widespread availability of nonoccupational postexposure prophylaxis against HIV.

OBJECTIVE: The aim of the study was to describe the use of nonoccupational postexposure prophylaxis (NPEP) in Australia, and to estimate the number of HIV infections that its use prevented. METHODS: We conducted a population-based observational cohort study of people who presented to antiretroviral prescribers in Eastern Australia, and reported a high-risk nonoccupational exposure to HIV, in 1998-2004. Prescribers collected data at baseline, 4 weeks and 6 months. Data collected included details of HIV exposure, drug regimens and HIV serostatus. RESULTS: The great majority of the 1601 participants were male (95%) and presented after male homosexual exposure (87%). Only 32% of exposures were to HIV-positive sources. Two antiretroviral drugs were prescribed after 48% of events, and three or more drugs after 52% of events. The median time to receipt of NPEP was 23 h. Side effects were reported by 66% of participants. No case of NPEP failure in an adherent individual was identified. It was estimated that 0.9-9.2 HIV infections had been prevented. This compared with a total of 1138 newly acquired HIV infections notified in the geographical area covered by the study. CONCLUSIONS: In Australia, NPEP has been widely prescribed and is mainly targeted at high-risk exposures. Although there were no identified failures of NPEP, it is likely that only a small proportion of new HIV infections in the study area were prevented. NPEP may be a valuable preventive intervention for an individual, but it can only play a minor role in HIV prevention at the population level unless targeting can be further improved.