Im Poynten

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

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.

Prevalence, incidence, and risk factors for human papillomavirus 16 seropositivity in Australian homosexual men.

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.

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

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.

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

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.

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

The aim of the study was to determine the cost‐effectiveness of HIV nonoccupational post‐exposure prophylaxis (NPEP) in Australia.

The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men.

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 p16INK4a/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.

The Evolving Design and Methods for Trials Evaluating the Safety of Candidate Vaginal Microbicides: A Systematic Review

Abstract Vaginal preexposure prophylaxis is a promising biomedical tool for HIV prevention. Although guidelines for the clinical assessment of microbicides are available, validated markers for product safety are lacking. To inform future microbicide and multipurpose vaginal product research, we reviewed the current and past safety methods used. We searched the Cochrane, EMBASE, and Ovid MEDLINE databases for clinical studies of vaginal products for the prevention of HIV that included safety evaluations. Ninety-seven clinical studies involving 21 products were identified: 63 lasted 14 days or less, 19 were longer in duration, and 15 were effectivess studies that included also safety as an outcome. Median sample size in the safety studies was 48 participants (range, 10–799). All studies reported on urogenital endpoint, 71% included colposcopy, and 67% assessed the vaginal microflora. Markers of vaginal epithelial inflammation, systemic absorption, and systemic toxicology assessments were evaluated in 29%, 26%, and 43% of studies, respectively. Excluding the effectiveness studies, these same assessments were done before 1998 in 33%, 7%, and 27% and after 2001 in 38%, 44%, and 60% of studies, respectively. Soluble inflammatory markers were introduced after 2001. Adverse event collection was reported in 73% of studies before 1998 and in 98% after 2001. In a previous review, we recommended that larger and longer safety studies were necessary to detect clinically important toxicities and to provide assurance that agents are ready for large-scale effectiveness trials. Here, we propose a stepwise clinical assessment that can be used for future guidance.

Validation of participant eligibility for pre-exposure prophylaxis: Baseline data from the PRELUDE demonstration project

Background In Australia, pre-exposure prophylaxis (PrEP) is targeted to individuals at high risk for HIV infection. We describe the HIV risk profile and characteristics of PRELUDE participants, and evaluate the population validity of the sample in representing high-risk gay and bisexual men (GBM) eligible for PrEP. Methods PRELUDE is an on-going, open-label, single-arm observational study. Participants were identified in clinics and screened for eligibility using a paper-based risk assessment tool which followed the New South Wales (NSW) PrEP guidelines. Selection was validated using an independent online behavioural survey, completed by study participants upon enrolment. Demographic information was analysed using descriptive statistics, and kappa tests were used to determine agreement between reporting of high-risk practices in the risk assessment and behavioural survey. Results During 2014–15, 471 individuals were targeted for enrolment; 341 were assessed for PrEP eligibility and 313 were enrolled. Of these, 303 (97%) identified as GBM. Overall, 85% of GBM met at least one high-risk criterion; 68% reported receptive intercourse with an HIV-positive or unknown status casual male partner, and 37% reported methamphetamine use in the three months preceding enrolment. The remaining 15% were enrolled based on medium-risk behaviours, or at the clinicians’ discretion. We found an 82% total agreement between self-reported high-risk behaviour and clinicians’ categorisation of GBM as being at high risk for HIV based on PrEP eligibility criteria. Conclusions Behavioural eligibility criteria used by clinicians successfully identified individuals at high risk for HIV infection. This targeted approach ensures that the greatest public health and HIV prevention benefits can be derived in a setting without universal access to PrEP.

Management of early anal cancer: need for guidelines and standardisation

PurposeThe optimal management of early squamous cell carcinoma of the anal canal (AC) is yet to be determined. This study investigated current practice in the management of early AC.MethodsA patterns of care survey was completed by Australian surgeons and radiation oncologists. Specific topics addressed were as follows: geographical location of practice, staging of disease, treatment approaches to T1N0 tumours and grade 3 anal intra-epithelial neoplasia (AIN3) lesions, radiotherapy planning, toxicities, follow-up and clinical trial involvement.ResultsSixty-four responses were obtained. For the management of T1N0 disease, half the respondents recommended standard dose chemo-radiotherapy (CRT) and one third recommended wide local excision (WLE). For the management of AIN3, half recommended WLE while a quarter advocated observation.ConclusionsThis study reveals a significant variation in the management of early AC. The development of guidelines specific to the treatment of early AC could standardise treatment while further research is required to define the optimal management of T1N0 AC and AIN.

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

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.