Biomedical prevention of sexually transmitted HIV

The control of the HIV epidemic is a momentous challenge. Despite successes in some situations, HIV transmission has not been adequately reduced by the HIV prevention methods currently available. This is demonstrated by the continuing spread of the HIV epidemic, mainly through sexual transmission. The approaches to HIV prevention have broadly been defined as structural, behavioural and biomedical. The objectives of this thesis were to examine the personal and public health impact of selected biomedical HIV prevention technologies on HIV acquisition and HIV risk behaviour and to explore a number of the specific scientific and methodological challenges encountered in the field of development of HIV prevention technologies. The following research aimed to add to the available Australian data on biomedical HIV prevention, and to determine the potential for future trials of HIV biomedical prevention in Australia.A number of key findings from this thesis contribute to knowledge in the area of biomedical HIV prevention research. Firstly, the design of published safety studies of candidate vaginal microbicides was not sufficient to detect potential toxic effects of these products. A second important contribution was the demonstration that there was no evidence of behavioural disinhibition after non-occupational post-exposure prophylaxis for HIV (NPEP) use. Thirdly, NPEP had an important protective effect against HIV acquisition at an individual level but not at a population level. Fourth, groups with high HIV incidence could be readily identified in low HIV incidence settings. Finally, men with higher levels of HIV risk were more willing to participate in clinical trials of biomedical HIV prevention technologies.The research in this thesis underlines the complex nature of biomedical HIV prevention research and HIV prevention implementation, from the design of clinical trials of candidate biomedical HIV prevention products, to identifying suitable study populations who are willing to take part in such trials and finally to implementing the use of such technologies. HIV prevention remains a global public health priority and it is imperative that efforts to identify safe and effective biomedical HIV prevention technologies continue

Any condomless anal intercourse is no longer an accurate measure of HIV sexual risk behaviour in gay and other men who have sex with men

Background: Condomless anal intercourse (CLAI) has long been recognised 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 behavioural 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 behaviour. 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 six 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 behaviour. As HIV prevention enters the era of antiretroviral-based biomedical approach, using all forms of CLAI indiscriminately as a measure of HIV behavioural risk is not helpful in understanding the current drivers of HIV transmission in the community

High adherence to HIV PrEP among clinic attendees over 12 months in the PRELUDE open-label demonstration project

Introduction: The efficacy of HIV pre-exposure prophylaxis (PrEP) depends upon adherence. Facilitated recall is a practical measure to monitor patients’ adherence to PrEP in clinical practice. Data from the PRELUDE Demonstration Project were used to investigate patterns and predictors of adherence to daily PrEP over 12 months. Methods: PRELUDE was an open-label study of high-HIV risk individuals taking PrEP in New South Wales, Australia. PrEP adherence was assessed quarterly for one year. Participants were asked by clinicians about the number of pills taken in the previous week (facilitated recall). Adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) for factors associated with daily adherence were calculated using generalised estimating equations for longitudinal data. Results: Of the 321 gay/bisexual men (GBM) enrolled in the study, 263 (82%) remained on study at month 12. Of these, 243 (92%) and 230 (87%) reported daily adherence (7 pills/week) at month and 12, respectively. Adherence declined by 10% during the study (aOR 0.90, 95%CI 0.84-0.95, p<0.001). In multivariate analysis, participants were more likely to report taking 7 pills in the previous week if they had engaged in group sex in the previous three months (aOR 1.33, 95%CI 1.15-1.53) or attended a private clinic (aOR 1.50, 95%CI 1.07-2.11). Conclusions: Among participants who completed one year of follow-up on PRELUDE, daily PrEP use was more likely among those at ongoing risk of HIV due to their behaviours. The moderate loss to follow-up in the cohort is not surprising, as individuals are not expected to remain on PrEP forever, but rather, during periods of risk. Combined, these results suggest that GBM in this study who are highly engaged with healthcare systems can identify times when they are at increased risk of contracting HIV and act accordingly, taking PrEP consistently as recommended during this time

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

Prevalence and risk factors associated with high-grade anal squamous intraepithelial lesions (HSIL)-AIN2 and HSIL-AIN3 in homosexual men

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. Keywords: Risk factors, Surrogate endpoints, HSIL, Cancer screening, Human papillomaviru