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.

Low HIV drug resistance prevalence among recently diagnosed HIV-positive men who have sex with men in a setting of high PrEP use.

INTRODUCTION: New South Wales (NSW) has one of the world's highest uptake rates of HIV pre-exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian-born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine/emtricitabine) resistance in settings of high PrEP use. Such an emergence could also increase treatment failure and associated clinical outcomes among people living with HIV (PLHIV). Despite low levels of nucleoside reverse-transcriptase inhibitor (NRTI) resistance relating to PrEP use in clinical settings, there are few published studies describing the prevalence of NRTI resistance among people newly diagnosed with HIV in a setting of high PrEP use. METHODS: Using HIV antiretroviral drug resistance data linked to NSW HIV notifications records of people diagnosed from 1 January 2015 to 31 December 2021 and with HIV attributed to male-to-male sex, we described trends in TFV and XTC resistance. Resistance was identified using the Stanford HIV Drug Resistance genotypic resistance interpretation system. To focus on transmitted drug resistance, resistance prevalence estimates were generated using sequences taken less than 3 months post-HIV diagnosis. These estimates were stratified by timing of sequencing relative to the date of diagnosis, year of sequencing, birthplace, likely place of HIV acquisition, and stage of HIV at diagnosis. RESULTS: Among 1119 diagnoses linked to HIV genomes sequenced less than 3 months following diagnosis, overall XTC resistance prevalence was 1.3%. Between 2015 and 2021, XTC resistance fluctuated between 0.5% to 2.9% and was 1.0% in 2021. No TFV resistance was found over the study period in any of the sequences analysed. Higher XTC resistance prevalence was observed among people with newly acquired HIV (evidence of HIV acquisition in the 12 months prior to diagnosis; 2.9%, p = 0.008). CONCLUSIONS: In this Australian setting, TFV and XTC resistance prevalence in new HIV diagnoses remained low. Our findings offer further evidence for the safe scale-up of PrEP in high-income settings, without jeopardizing the treatment of those living with HIV.

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.

Predicting vaccine effectiveness for mpox.

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.

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.

A proposal for a simplified measure of HIV preexposure prophylaxis prevention-effective adherence in self-report questionnaires.

Evaluating HIV preexposure prophylaxis (PrEP) use and HIV risk events concurrently remains challenging. We developed a single question method for measuring prevention-effective adherence with PrEP in self-report questionnaires. In a questionnaire completed by 409 gay and bisexual men, 46% reported condomless anal sex that was not covered by their own PrEP use, and this was more common among younger, lower-income participants. Refining this questionnaire item could improve measurement of prevention-effective adherence.

Sexual pleasure and HIV-related worry in female sex workers on oral pre-exposure prophylaxis in south-western Uganda.

BACKGROUND: Female sex workers (FSWs) contribute disproportionately to HIV transmission in Uganda, and pre-exposure prophylaxis (PrEP) is effective in preventing HIV among cisgender women. Psychological factors are important for PrEP uptake, but few studies have examined psychosocial changes due to PrEP use in Uganda. METHODS: In 2021, we recruited 524 FSWs in three Trans-African Highway towns and four fishing communities in south-western Uganda. We conducted structured interviews among women who were attending routine PrEP follow-up visits in six health units. Bivariable and multivariable modified regression using a robust covariance matrix estimator were used to identify factors associated with experiencing increased sexual pleasure and less worry about HIV because of PrEP. RESULTS: Overall, 80.9% participants reported that sex was more pleasurable because of taking PrEP. There were statistical trends for sex being more pleasurable when taking PrEP or when having condomless sex with casual paying partners (aPR=1.19, 95% CI=1.07-1.32, P =0.001). Almost three-quarters of the participants (76.3%) were less worried about getting HIV because of PrEP. Condomless sex with casual paying partners (aPR=1.17, 95% CI=1.05-1.31, P =0.032, P =0.003) and being On PrEP for the past 1-2years (aPR=1.18, 95% CI=1.00-1.38, P =0.032) was significantly associated with HIV-related worry (aPR=1.17, 95% CI=1.05-1.31, P =0.032, P =0.003) Conclusions : We found a positive impact of PrEP in Ugandan FSWs on two key psychosocial dimensions: (1) more pleasurable sex; and (2) less worry about acquiring HIV. Interventions aiming to increase PrEP uptake may find it useful to focus on psychosocial dimensions.

Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.

Trends in Testing and Self-Reported Diagnoses of Sexually Transmitted Infections in Gay and Bisexual Men in Australia, 2017 to 2021: Analysis of National Behavioral Surveillance Surveys.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBM) are overrepresented in diagnoses of sexually transmitted infections (STIs) relative to their population size. This study assessed trends in STI testing and diagnoses among GBM in Australia. METHODS: The Gay Community Periodic Surveys are repeated cross-sectional behavioral surveillance surveys of GBM. Participants reported the number of anal swabs, throat swabs, urine samples, and blood tests for syphilis they undertook in the last year. "Frequent comprehensive testing" was defined as ≥3 of each test in the previous year. Participants reported STI diagnoses of chlamydia, gonorrhea, syphilis, and other STIs in the last year. Trends in testing and diagnoses from 2017 to 2020 and 2020 to 2021 were assessed with logistic regression models. RESULTS: We analyzed 24,488 survey responses from participants reporting casual sex in the last 6 months. Between 2017 and 2020, frequent comprehensive STI testing decreased among HIV-negative GBM on preexposure prophylaxis (PrEP) from 71.7% to 68.9% and declined further to 58.6% in 2021. Frequent comprehensive STI testing was stable during 2017-2020 among HIV-negative/untested GBM not on PrEP (17.4%-14.6%) and HIV-positive GBM (30.4%-35.1%) but declined in 2021 to 7.5% among non-PrEP-users and 25.7% among HIV-positive participants. There were minimal changes in STI diagnoses during 2017-2020, but diagnoses declined in 2021. CONCLUSIONS: Many GBM do not meet Australian STI testing guidelines that recommend quarterly testing. Further evaluation of whether this recommendation is realistic or necessary to reduce STIs among GBM is recommended.

HIV treatment-as-prevention and its effect on incidence of HIV among cisgender gay, bisexual, and other men who have sex with men in Australia: a 10-year longitudinal cohort study.

BACKGROUND: Although HIV treatment-as-prevention reduces individual-level HIV transmission, population-level effects are unclear. We aimed to investigate whether treatment-as-prevention could achieve population-level reductions in HIV incidence among gay, bisexual, and other men who have sex with men (GBM) in Australia's most populous states, New South Wales and Victoria. METHODS: TAIPAN was a longitudinal cohort study using routine health record data extracted from 69 health services that provide HIV diagnosis and care to GBM in New South Wales and Victoria, Australia. Data from Jan 1, 2010, to Dec 31, 2019, were linked within and between services and over time. TAIPAN collected data from all cisgender GBM who attended participating services, resided in New South Wales or Victoria, and were 16 years or older. Two cohorts were established: one included HIV-positive patients, and the other included HIV-negative patients. Population prevalence of viral suppression (plasma HIV viral load <200 RNA copies per µL) was calculated by combining direct measures of viral load among the HIV-positive cohort with estimates for undiagnosed GBM. The primary outcome of HIV incidence was measured directly via repeat testing in the HIV-negative cohort. Poisson regression analyses with generalised estimating equations assessed temporal associations between population prevalence of viral suppression and HIV incidence among the subsample of HIV-negative GBM with multiple instances of HIV testing. FINDINGS: At baseline, the final sample (n=101 772) included 90 304 HIV-negative and 11 468 HIV-positive GBM. 59 234 patients in the HIV-negative cohort had two or more instances of HIV testing and were included in the primary analysis. Over the study period, population prevalence of viral suppression increased from 69·27% (95% CI 66·41-71·96) to 88·31% (86·37-90·35), while HIV incidence decreased from 0·64 per 100 person-years (95% CI 0·55-0·76) to 0·22 per 100 person-years (0·17-0·28). Adjusting for sociodemographic characteristics and HIV pre-exposure prophylaxis (PrEP) use, treatment-as-prevention achieved significant population-level reductions in HIV incidence among GBM: a 1% increase in population prevalence of viral suppression corresponded with a 6% decrease in HIV incidence (incidence rate ratio [IRR] 0·94, 95% CI 0·93-0·96; p<0·0001). PrEP was introduced in 2016 with 17·60% uptake among GBM that year, which increased to 36·38% in 2019. The relationship between population prevalence of viral suppression and HIV incidence was observed before the availability of PrEP (IRR 0·98, 95% CI 0·96-0·99; p<0·0001) and was even stronger after the introduction of PrEP (0·80, 0·70-0·93; p=0·0030). INTERPRETATION: Our results suggest that further investment in HIV treatment, especially alongside PrEP, can improve public health by reducing HIV incidence among GBM. FUNDING: National Health and Medical Research Council of Australia.

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.

Factors Associated With Willingness to Use Daily Antibiotics as Sexually Transmitted Infection Prophylaxis Among HIV Preexposure Prophylaxis-Experienced Gay and Bisexual Men in Australia.

BACKGROUND: Gay and bisexual men (GBM) who use HIV preexposure prophylaxis (HIV-PrEP) have high rates of bacterial sexually transmitted infections (STIs). The use of daily antibiotics as STI preexposure prophylaxis (STI-PrEP) may be appealing to GBM who are using or have previously used HIV-PrEP (HIV-PrEP-experienced) for the prevention of bacterial STIs. METHODS: We examined willingness to use daily STI-PrEP among a cross-sectional sample of HIV-PrEP-experienced GBM in Australia who participated in an observational online cohort study from August 2018 to March 2020. Factors associated with willingness to use daily STI-PrEP were determined using bivariate and multivariate logistic regression. RESULTS: Of the 1347 participants, half (54.3%) were willing to use daily STI-PrEP. Factors independently associated with greater willingness to use daily STI-PrEP included having >10 sexual partners in the last 6 months, using methamphetamine in the last 6 months, being more conscious about avoiding STIs, having a greater number of STIs since commencing HIV-PrEP, being willing to take HIV-PrEP for as long as they were at risk of acquiring HIV, and only using condoms when a sexual partner requested them. Conversely, factors associated with less willingness to use daily STI-PrEP included being university educated, using nondaily dosing regimens of HIV-PrEP, preferring event-driven HIV-PrEP, and being concerned about long-term HIV-PrEP adverse effects. CONCLUSIONS: Sexually transmitted infection PrEP is likely to be appealing to many HIV-PrEP-experienced GBM, especially those who engage in activities associated with a higher risk of STI transmission. However, they are less likely to be willing to use STI-PrEP unless it aligns with their HIV-PrEP dosing regimen, suggesting that research into the safety and efficacy of alternative STI prophylaxis dosing options should be prioritized.

Identifying Patterns of Discontinuing and Recommencing Pre-exposure Prophylaxis in the Context of Sexual Behavior Among Gay and Bisexual Men in Australia.

We mapped gay and bisexual men's (GBM) patterns of using pre-exposure prophylaxis (PrEP) over time and explored sexual behavior as PrEP use changed. We conducted semi-structured interviews between June 2020 and February 2021 with 40 GBM living in Australia who had changed their PrEP use since initiating. There was considerable diversity in patterns of discontinuation, suspension, and recommencement of PrEP. Reasons for changing PrEP use mostly centered on accurate perceived changes to HIV risk. Twelve participants reported condomless anal intercourse with casual or fuckbuddy partners after discontinuing PrEP. These sex events were unanticipated, condoms were not a preferred option, and other risk reduction strategies were applied inconsistently. Service delivery and health promotion can support safer sex among GBM when PrEP use fluctuates by promoting event-driven PrEP and/or non-condom-based risk reduction methods during periods off daily PrEP, and guiding GBM to better recognize changing circumstances of risk and when to recommence PrEP.

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.

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.

Self-reported and pill count measures of adherence to oral HIV PrEP among female sex workers living in South-Western Uganda.

BACKGROUND: Female sex workers (FSWs) in Uganda are at high risk of HIV infection. Scaling up oral pre-exposure prophylaxis (PrEP) will reduce HIV incidence if high levels of adherence are maintained. This study evaluates PrEP adherence using clinic-based pill counts and self-reported measures, and factors associated with protective levels of adherence. METHODS: Participants were sex workers who had been taking PrEP for at least 5 months and were attending routine follow-up visits for PrEP care in fishing communities and along the Trans-African Highway. Participants who had a pill count showing at least 85% use since their last clinic visit and those who reported taking their PrEP every day in the last 5 months were categorised as having 'protective adherence'. Spearman's correlation and weighted kappa assessed the relationship between pill count and self-reported measures. Bivariate and multivariate logistic regression was used to determine factors associated with protective adherence as measured by pill count. RESULTS: We recruited 524 FSWs, with a median age of 29 years (IQR 23-35). Participants were recruited from fishing communities and Trans-African Highway towns (n = 297, 56.7%, and n = 227, 43.0%). Nearly three quarters (n = 372, 71.0%) of women were estimated to have protective adherence based on pill count (i.e., a pill count of >85%) and 50.4% by self-report in last 3 months. There was a strong positive association between self-reported measures and pill count measures (rest = 0.6453, 95% CI = 0.5924-0.6927) and a moderate agreement between self-reported measures and pill count measures, κ = 0.544 (95%CI = 0.4869-0.6011, p < 0.001). Factors associated with protective adherence included being aged 35 years or older (aOR = 2.40, 95% CI = 1.17-4.86), living in a fishing community (aOR = 1.45, 95% CI = 0.62-3.38), and having an STI in last 3 months (aOR = 1.64, 95% CI = 1.07-2.49). CONCLUSION: Our findings indicate that PrEP-experienced FSWs attending clinical follow-up visits reported high protective levels of oral pre-exposure prophylaxis, as measured by both pill count and self-reported measures, and a moderate agreement between pill count and self-reported measures.

Experiences of recently HIV-diagnosed gay and bisexual migrants in Australia: Implications for sexual health programmes and health promotion.

Gay and bisexual migrants from low- and middle-income countries living in high-income countries are disproportionately diagnosed with HIV. Most research focuses on preventing HIV acquisition among HIV-negative migrant gay and bisexual men (GBM). This study is uniquely positioned to report on migrant GBM's experiences and needs at and after an HIV diagnosis. Semi-structured interviews were conducted with 24 migrant GBM diagnosed at sexual health clinics in Australia from 2017 onwards. Interviews were analysed using a codebook thematic analysis. Due to the stigma of HIV and homosexuality in their countries of origin, about half of participants had poor HIV knowledge prior to diagnosis. Absorbing diagnosis information was consequently difficult, and feelings of shame, hopelessness, lost sexual opportunities and infectiousness were common. However, many were thankful for the comprehensive clinical support they received and believed that over time life would 'normalise' with sustained undetectable viral load. None reported that their clinician stigmatised them, but the anticipation of stigma nonetheless infused their experiences after diagnosis. Many were selective about HIV disclosure, and some mentioned that clinic systems posed a risk to confidentiality. Non-permanent residents were concerned about the impacts of HIV status on future visa applications. We recommend that newly HIV-diagnosed migrant GBM receive referral to legal and culturally appropriate migration services to help absorb what a diagnosis might mean for their health and visa status. We also recommend sexual health clinics continue to assess confidentiality in their systems. Health promotion initiatives should highlight to migrant GBM that high-HIV caseload sexual health clinicians provide confidential and comprehensive care.