Does use of anal cytology as a triage test improve the performance of high-risk human papillomavirus screening in gay and bisexual men for anal cancer prevention?

Anal high-risk human papillomavirus (HRHPV) testing-based anal cancer screening gay and bisexual men (GBM) is associated with high sensitivity, but low specificity. We report the potential role of triage use of anal cytology with HRHPV testing in detecting 12-month persistent anal high-grade squamous epithelial lesions (HSIL) in a cohort of GBM in Sydney, Australia. Participants were GBM from the Study of the Prevention of Anal Cancer (SPANC) who underwent annual anal HPV testing, cytology, and high-resolution anoscopy (HRA)-guided histology. The sensitivity and specificity of five screening algorithms based on HRHPV test results with triage use of anal cytology (atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude HSIL (ASC-H) used as referral thresholds) were compared to these of HRHPV testing and anal cytology alone. A total of 475 men who had valid HRHPV, cytological, and histological results at both baseline and first annual follow-up visits were included, median age 49 years (inter-quartile range: 43-56) and 173 (36.4%) GBM with human immunodeficiency virus. Of all triage algorithms assessed, two had comparable sensitivity with HRHPV testing alone in detecting persistent anal HSIL, but ~20% higher specificity and 20% lower HRA referral rates. These two algorithms involved the immediate referral of those with HPV16 and for those with non-16 HRHPV either immediate or delayed (for 12 months) referral, depending on cytology result at baseline. Triage use of anal cytology in GBM testing positive for anal HRHPV increases specificity and reduces referral rates while maintaining high sensitivity in detection of HSIL.

Self-collected versus clinician-collected anal swabs for anal cancer screening: A systematic review and meta-analysis.

Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.

Condom Failure Among HIV-Negative Men in Serodiscordant Relationships in Australia, Brazil, and Thailand.

Condoms continue to be used by many gay, bisexual, and other men who have sex with men (GBM) to reduce the risk of HIV transmission. However this is impacted by condom failure events, defined here as condom breakage and slippage. In a prospective, observational cohort study of 343 HIV serodiscordant male couples recruited through high HIV caseload clinics and hospitals between 2012 and 2016 in Australia, Brazil, and Thailand, condom failure rates and associated factors were analysed, including with the study partner versus other sexual partners. There were 717 reported instances of condom failure from an estimated total of 25,831 sex acts with condoms, from over 588.4 participant years of follow up. Of the HIV-negative partners (n = 343) in the study, more than a third (n = 117, 36.7%) reported at least one instance of condom failure with any partner type during study follow-up. Condom failure with their study partner was reported by 91/343 (26.5%) HIV-negative partners, compared with 43/343 (12.5%) who reported condom failure with other partners. In total, there were 86 events where the HIV-negative partner experienced ano-receptive condom failure with ejaculation, representing 12.0% of all failure events. In multivariable analysis, compared to Australia, HIV-negative men in Brazil reported a higher incidence risk rate of condom failure (IRR = 1.64, 95%CI 1.01-2.68, p = 0.046) and HIV-negative men who reported anal sex with other partners reported an increased risk of condom failure compared with men who only had sex with their study partner (IRR = 1.89, 95%CI 1.08-3.33, p = 0.025). Although at least one event of condom failure was reported by a significant proportion of participants, overall condom failure events represented a small proportion of the total condom protected sex acts.

Cancer risk in people living with HIV and solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. METHODS: We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. FINDINGS: 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. INTERPRETATION: Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. FUNDING: US National Cancer Institute, National Institutes of Health.

Factors Associated With Recent Decline in Anal Health Among Older Gay and Bisexual Men: A Cross-sectional Analysis.

ABSTRACT: We investigated factors associated with "worse than usual" anal health among gay and bisexual men aged ≥35 years recruited to a longitudinal study of anal human papillomavirus infection/lesions from September 2010 to August 2015.Among 616 participants (median age 49 years; 36% HIV-positive), 42 (6.8%) reported worse than usual anal health in the last 4 weeks. Associated factors included spending less time with gay friends (odds ratio [OR] = 2.25, 95% CI = 1.06-4.77), most time "feeling down"(OR = 9.17, 95% CI = 2.94-28.59), reduced libido (OR = 2.90, 95% CI = 1.52-5.52), current anal symptoms (OR = 6.55, 95% CI = 2.54-16.90), recent anal wart diagnosis (OR = 4.33, 95% CI = 1.98-9.49), and fear of developing anal cancer (OR = 9.34, 95% CI = 4.52-19.28).Concerns regarding anal health should be routinely discussed by clinicians, and potentially associated psychosocial, physical, and sexual issues further explored.

Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Anal cancer: a 20-year retrospective study from Australia.

BACKGROUNDS: Anal cancer is an uncommon condition, occurring at higher rates in specific subpopulations. Clinical experience is limited and substantial changes have recently occurred in our understanding of this condition. We, therefore, set out to characterize patients presenting with anal cancer and investigate whether there have been any changes over the past 20 years. METHODS: Retrospective audit of cases identified from pathology and clinical databases during the period 1 January 2000 to 31 December 2019. RESULTS: Two hundred and sixteen patients had anal squamous cell carcinomas, comprising 160 (74%) males and 56 (26%) females. Mean age at initial diagnosis was 55.1 ± 11.20 for males and 60.6 ± 15.18 for females (P = 0.02). At initial diagnosis, HIV-positive cases were significantly younger than HIV negative cases (mean 52.2 ± 9.35 vs. 62.8 ± 11.61, P < 0.001); 46% of cases were classified as intra-anal, 29% perianal and 25% both; 52% were > 2 cm at diagnosis. At presentation, intra-anal cases were larger and more advanced than perianal cases (P = 0.049). Compared with the period 2000-2009, anal cancers presented more commonly in 2010-2019 (148 vs. 76), were more likely to occur in HIV-negative people and to be diagnosed at a similar stage. CONCLUSION: The number of anal cancer cases almost doubled over the study period and people living with HIV presented 10 years younger than others. Perianal cases presented earlier than those originating in intra-anal locations. Together with the large size at diagnosis, this suggests the potential value of screening, particularly for intra-anal cancers in those at high risk.

Agreements, Behaviour, and Change: Sex Outside the Relationship in Male HIV-negative Partners in HIV Serodiscordant Relationships in Australia, Brazil, and Thailand.

Male HIV serodiscordant couples have diverse relationship agreements regarding sex outside the relationship. We examined the relationship agreements as described by 343 male HIV-negative partners in HIV serodiscordant relationships in Australia, Brazil and Thailand participating in a multi-year cohort study. At baseline, 125 (34.1%) HIV-negative partners reported no agreement, 115 (33.5%) had a monogamous agreement, and 103 (37.9%) had an open agreement allowing sex outside the relationship. Relationship agreements were largely stable over time, with 76% of HIV-negative men reporting the same agreement across follow up, while changes were predominantly towards having an open agreement. Behaviour largely matched relationship agreements, and the predictors of breaking an agreement by having condomless anal intercourse (CLAI) with an outside partner were CLAI within the relationship (OR = 3.17, 95%CI: 1.64-6.14, p < 0.001) and PrEP use in the last three months (OR = 3.42, 95%CI: 1.48-7.92, p = 0.004). When considering HIV transmission risk for HIV-negative men in serodiscordant relationships, greater focus needs to be placed on sex that is occurring outside the relationship and the agreements that facilitate this.

Second Primary Cancers in People With HIV/AIDS: A National Data Linkage Study of Incidence and Risk Factors.

BACKGROUND: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. SETTING: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012. METHODS: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count. RESULTS: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14). CONCLUSIONS: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Cost-effectiveness of screening and treating anal pre-cancerous lesions among gay, bisexual and other men who have sex with men living with HIV.

Background: Gay, bisexual and other men who have sex with men (GBM) living with HIV have a substantially elevated risk of anal cancer (85 cases per 100,000 person-years vs 1-2 cases per 100,000 person-years in the general population). The precursor to anal cancer is high-grade squamous intraepithelial lesion (HSIL). Findings regarding the cost-effectiveness of HSIL screening and treatment in GBM are conflicting. Using recent data on HSIL natural history and treatment effectiveness, we aimed to improve upon earlier models. Methods: We developed a Markov cohort model populated using observational study data and published literature. Our study population was GBM living with HIV aged ≥35 years. We used a lifetime horizon and framed our model on the Australian healthcare perspective. The intervention was anal HSIL screening and treatment. Our primary outcome was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life-year (QALY) gained. Findings: Anal cancer incidence was estimated to decline by 44-70% following implementation of annual HSIL screening and treatment. However, for the most cost-effective screening method assessed, the ICER relative to current practice, Australian Dollar (AUD) 135,800 per QALY gained, remained higher than Australia's commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained. In probabilistic sensitivity analyses, HSIL screening and treatment had a 20% probability of being cost-effective. When the sensitivity and specificity of HSIL screening were enhanced beyond the limits of current technology, without an increase in the cost of screening, ICERs improved but were still not cost-effective. Cost-effectiveness was achieved with a screening test that had 95% sensitivity, 95% specificity, and cost ≤ AUD 24 per test. Interpretation: Establishing highly sensitive and highly specific HSIL screening methods that cost less than currently available techniques remains a research priority. Funding: No specific funding was received for this analysis.

Discontinuation of government subsidized HIV pre-exposure prophylaxis in Australia: a whole-of-population analysis of dispensing records.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has been government subsidized in Australia since April 2018 and while uptake is high among men who have sex with men, rates of discontinuation are also high. The aims of this study were to examine the impact of discontinuation on overall PrEP usage, the proportion of PrEP users who discontinue and the predictors of discontinuation. METHODS: We used linked de-identified dispensing records of all government subsidized PrEP in Australia between April 2018 and September 2021: a whole-of-population data set. Defining discontinuation as 180 days or more without PrEP after the final dispensed supply, we calculated the number of people who discontinued at each 6-month interval during the study period, the proportion who had discontinued 2 years after the first supply and, using Cox regression, predictors of discontinuation. RESULTS: Of 49,164 people dispensed PrEP (98.5% male, median age 34 years), 40.3% (19,815) had discontinued by September 2021. Within 2 years of their first supply, 11,150 (37.7%) of 29,549 PrEP users had discontinued, including 10.0% after a single dispensed supply. Large variations were observed, particularly according to prescriber characteristics: discontinuation was higher among people prescribed PrEP by low caseload (≤10 patients) prescribers (61.2%) than by high caseload (>100 patients) prescribers (31.1%, p<0.001), and by prescribers practising in areas with low estimated prevalence (<1.0%) of gay men (64.1%) than high (>5%) prevalence (36.7%, p<0.001). Women and younger people were more likely to discontinue, while patients receiving a higher level of government subsidy were less likely. The independent predictors of discontinuation with the greatest effect size were female sex (adjusted hazards ratio [aHR] 2.99, p<0.001), low estimated gay prevalence of prescriber location (aHR 1.98, p<0.001) and low prescriber PrEP caseload (aHR 1.79, p<0.001). CONCLUSIONS: There are high rates of PrEP discontinuation in Australia and some populations are at increased risk of discontinuation. Strategies are needed to support persistence on PrEP and the re-starting of PrEP during periods of risk.

Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.

Relationship Between Sexual Behaviors with Non-committed Relationship Partners and COVID-19 Restrictions and Notification Rates: Results from a Longitudinal Study of Gay and Bisexual Men in Australia.

Introduction: COVID-19 related lockdowns have impacted the sexual activity of gay and bisexual men (GBM). We investigated trends in sexual behaviors and the COVID-19 context in which they occurred (COVID-notification rates and jurisdictional restrictions) to understand changes in the duration and severity of periods of lockdown on the sexual behavior of Australian GBM. Methods: In an online, prospective observational study of 831 GBM from May 2020 to May 2021, we investigated associations between changes in sexual behavior among Australian GBM, lockdowns, and COVID-19 notification rates through weekly surveys from May 2020 to May 2021. Results: The mean age was 45.71 years (SD: 13.93). Most identified as gay (89.0%) and 10.2% were living with HIV. There was an overall increase in the mean weekly number of non-committed relationship partners (0.53-0.90, p < 0.001). The state of Victoria experienced a significant extended COVID-19 outbreak, accompanied by severe lockdown restrictions. In response, Victorian men's partner numbers shifted three times, while elsewhere there was an overall gradually increasing trend. Conclusions: Less severe outbreaks with shorter lockdown periods, involving fewer and geographically contained, COVID-19 notifications were accompanied by non-significant changes in sex with non-relationship partners than more severe outbreaks over extended periods and larger geographical areas. Supplementary Information: The online version contains supplementary material available at 10.1007/s13178-022-00733-8.

How to have sex in a pandemic: the development of strategies to prevent COVID-19 transmission in sexual encounters among gay and bisexual men in Australia.

Although many studies reported on decreases in sexual partner numbers among gay and bisexual-identifying men in the early period of the COVID-19 pandemic, few studies have explored COVID-19 risk-reduction strategies. Drawing on free-text responses in an online survey (from April to July 2020), we describe the ways in which men sought to minimise the risk of COVID-19 in sexual encounters. Partner selection was an important strategy, in particular, restricting sex to men they already knew. Accounts also indicate how participants assessed risk from potential sex partners based on symptoms, residential location, recent travel, work role, and number of other sexual contacts. Less common were in situ practices, such as avoiding kissing. Participants' responses provide insight into creative community-based responses in the early months of the pandemic, some of which have resonances with early responses to HIV. Findings are discussed in relation to the concepts of 'lay epidemiology' and 'counterpublic health'. In particular, we examine how risks and health are experienced and valued in relation to local knowledges, meanings, and practices; and how practices emerge in response to dominant public health discourses that produce an idealised public based on (hetero)normative assumptions.

COVID-19 Testing in a Weekly Cohort Study of Gay and Bisexual Men: The Impact of Health-Seeking Behaviors and Social Connection.

Gay, bisexual, and other men who have sex with men (GBM) have developed community norms for regular HIV/STI testing. We investigated factors associated with self-reported COVID-19 testing in response to reported COVID-19 cases and public health restrictions. Participants responded to weekly cohort surveys between 10th May 2021 and 27th September 2021. We used the Andersen-Gill extensions to the Cox proportional hazards model for multivariable survival data to predict factors influencing COVID-19 testing. Mean age of the 942 study participants was 45.6 years (SD: 13.9). In multivariable analysis, GBM were more likely to report testing during periods of high COVID-19 caseload in their state of residence; if they were younger; university educated; close contact of someone with COVID-19; or reported coping with COVID-19 poorly. COVID-19 testing was higher among men who: were more socially engaged with other GBM; had a higher proportion of friends willing to vaccinate against COVID-19; and were willing to contact sexual partners for contact tracing. Social connection with other gay men was associated with COVID-19 testing, similar to what has been observed throughout the HIV epidemic, making community networks a potential focus for the promotion of COVID-19 safe practices.

Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.

Comparison of four assays for human papillomavirus detection in the anal canal.

OBJECTIVE: Anal cancer is preceded by high-risk human papillomavirus (HRHPV) infection, predominantly HPV16. No HPV assay is licenced for use in anal screening. We aimed to determine the sensitivity and specificity of four anal canal swab HPV assays to predict high-grade squamous epithelial lesions (HSIL). METHODS: In a cohort of Australian HIV-positive and negative gay and bisexual men, we compared the sensitivity and specificity of detection of 13 anal HRHPV genotypes by Linear Array (LA), Cobas 4800, EuroArray, and Anyplex II HPV28 (+ and ++ cut offs), compared their ability to predict prevalent anal HSIL, and compared anal canal HRHPV detection with HRHPV isolated from HSIL using laser capture microdissection (LCM). RESULTS: A total of 475 participants had baseline results available for all four assays (166, 35.0% HIV positive), and 169 participants had a diagnosis of cytological and/or histological HSIL. The HPV16 and any HRHPV detection were highest with Anyplex II HPV28 (+) (156, 32.8% 95% CI 28.6-37.2 and 359, 75.6%, 95% CI 71.5-79.4, respectively). For detection of concurrent HSIL and HPV16, the assay sensitivity was similar, ranging from 49.1%, 95% CI 41.4-56.9 (Anyplex II HPV28 ++) to 55.0%, 95% CI 47.2-62.7 (Anyplex II HPV28 +). For concurrent HSIL and any HRHPV detection, EuroArray was more specific than Anyplex II HPV28 (+) (45.9% 95% CI 40.2-51.7 vs 36.7%, 95% CI 31.3-42.4, p = 0.021) and had comparable specificity with Anyplex II HPV28 (++) (45.9% vs 47.2%, 95% CI 41.5-53.0, p = 0.75). All assays had high sensitivities for predicting HPV16 detected on LCM (92.5-97.5%). Anyplex II HPV28 and EuroArray were significantly more sensitive than LA for lesions caused by non-HPV16 HRHPV types on LCM. DISCUSSION: Anyplex II HPV28 and EuroArray detected more non-16 HRHPV genotypes than LA. Increasing the Anyplex II HPV28 cutoff improved specificity without compromising sensitivity for detection of concurrent HSIL.

Low Prior Exposure and Incidence of Hepatitis C in Human Immunodeficiency Virus-Negative Gay and Bisexual Men Taking Preexposure Prophylaxis (PrEP): Findings From the Expanded PrEP Implementation in Communities-New South Wales Prospective Implementation Study.

BACKGROUND: The use of preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has raised concerns of increased sexual risk behaviors. These behaviors may be associated with increased incidence of sexually acquired hepatitis C virus (HCV) among gay and bisexual men. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study was a cohort study of daily coformulated tenofovir disoproxil fumarate and emtricitabine for HIV prevention. We recruited 9596 people at high risk of HIV acquisition from 31 clinics across New South Wales and the Australia Capital Territory in Australia. We report prior exposure to HCV and incidence in this cohort between 2016 and 2019. RESULTS: At least 1 HCV test result was available for 8658 (90.2%) participants. These individuals had a median age of 34 years (interquartile range, 28-43), most of whom were male (8530, 98.5%), identified as gay (7944, 91.8%), and were born in Australia (51.8%). Prior exposure to HCV was detected among 81 participants at baseline (0.9%; 95% confidence interval [CI]: .71.2). Twenty of 8577 participants were diagnosed with incident infection (rate 0.2/100 person-years [95% CI: .1-.3/100 person-years]). They were significantly older (median age 41 years vs 34 years, P = .044), and more likely to report methamphetamine use at baseline (incidence rate ratio, 2.7 [95% CI: 1.00-7.2]) than those without incident infection. CONCLUSIONS: In this population of PrEP users, HCV prior exposure and incidence were low. With high levels of HCV and HIV testing and treatment, the dual goals of HIV and HCV elimination could be achieved in this population. Clinical Trials Registration: number NCT02870790.