Use of doxycycline and other antibiotics as bacterial sexually transmitted infection prophylaxis in a U.S. sample of primarily gay and bisexual men.

BACKGROUND: Doxycycline used as post-exposure prophylaxis (doxyPEP) within 72 hours of sex reduces the risk of bacterial sexually transmitted infections (STIs) in people assigned male sex at birth. Little is known about current use of antibiotics as STI prophylaxis in U.S. populations likely to benefit from doxyPEP. METHODS: We conducted an online survey in September 2023 of U.S. adults recruited via sexual networking apps used mainly by gay and bisexual men (GBM). Respondents were asked about the use of antibiotics around the time of sex to prevent bacterial STIs. RESULTS: Of 903 respondents, most (96.2%) identified as GBM; 19.0% were living with HIV and 42.5% using HIV pre-exposure prophylaxis. Half (49.1%) had heard of using antibiotics to prevent STIs and 95.6% were interested in use. Overall, 21.0% had used antibiotic STI prophylaxis and 15.9% had done so in the past year. Among those reporting any use, most (78.1%) had used doxycycline; some used amoxicillin (16.7%), azithromycin (14.5%), or other antibiotics (14.1%). Among those reporting use in the past year, 46.9% used it for some, 28.1% for most, and 25.0% for all sex acts with casual partners during that period. Most (78.3%) of STI prophylaxis users reported their condom use did not change during periods of STI prophylaxis use, 17.2% indicated their condom use declined, and 4.5% indicated their condom use increased. For doxyPEP specifically, 35.7% had heard of it and 13.0% had used it in the past year, of whom 21.0% had used a dosage other than the 200 mg dose shown to be effective. CONCLUSIONS: In this sample of primarily GBM, interest in bacterial STI prophylaxis was nearly universal. However, some of the use was not informed by current clinical guidance or evidence from research studies. Efforts are needed to increase awareness of effective dosing and monitor real-world use.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

BACKGROUND: There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. METHODS: Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. RESULTS: Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). CONCLUSION: HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

Potential impact of doxycycline post-exposure prophylaxis prescribing strategies on incidence of bacterial sexually transmitted infections.

BACKGROUND: Doxycycline post-exposure prophylaxis (doxyPEP) reduces bacterial sexually transmitted infection (STI) incidence in people with HIV (PWH) or using HIV preexposure prophylaxis (PrEP). Given concerns about widespread antibiotic use, we identified doxyPEP prescribing strategies to minimize use while maximizing impact on STIs. METHODS: We used electronic health records of gay and bisexual men (GBM), transgender women, and non-binary people assigned male sex at birth with ≥2 STI tests (chlamydia, gonorrhea, syphilis) at an LGBTQ-focused health center during 2015-2020. We defined 10 hypothetical doxyPEP prescribing strategies based on PrEP use, HIV status, or STI history. We estimated doxyPEP use and STI diagnoses averted in counterfactual scenarios in which people meeting prescribing criteria received doxyPEP, assuming STI rates during use would have been reduced by clinical trial efficacy estimates. RESULTS: Among 10,546 individuals (94% GBM), rate of any STI was 35.9/100 person-years. Prescribing doxyPEP to all individuals would have averted 71% of STI diagnoses (number needed to treat for one year to avert one STI diagnosis, NNT = 3.9); prescribing to PrEP users/PWH (52%/12% of individuals) would have averted 60% of STI diagnoses (NNT = 2.9). Prescribing doxyPEP for 12 months after STI diagnosis would have reduced the proportion using doxyPEP to 38% and averted 39% of STI diagnoses (NNT = 2.4). Prescribing after concurrent or repeated STIs would have maximized efficiency (lowest NNTs) but prevented fewer STIs. CONCLUSIONS: Prescribing doxyPEP to individuals with STIs, particularly concurrent or repeated STIs, could avert a substantial proportion of all STI diagnoses. The most efficient prescribing strategies are based on STI history rather than HIV status or PrEP use.

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.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

The impact of point-of-care hepatitis C testing in needle and syringe exchange programs on linkage to care and treatment uptake among people who inject drugs: An Australian pilot study.

Point-of-care (POC) diagnostics overcome barriers to conventional hepatitis C (HCV) testing in people who inject drugs. This study assessed impact on hepatitis C treatment uptake of POC HCV testing in needle and syringe exchange programs (NSPs). Rapid EC was a single-arm interventional pilot study of HCV POC testing conducted in three inner-city community clinics with NSPs. Twelve months after the POC testing, a retrospective medical record and Pharmaceutical Benefits Scheme audit was performed to determine the number of HCV RNA-positive participants who were prescribed HCV treatment. 70 HCV RNA-positive Rapid EC study participants were included. 44 (63%) were prescribed DAAs; 26 (59%) completed treatment and 15 (34%) had SVR testing, all of whom were cured. Age ≥ 40 years (aOR 3.45, 95% CI 1.10-11.05, p = .03) and secondary school education (aOR 5.8, 95% CI 1.54-21.80, p = .009) had higher likelihood of being prescribed DAAs, whereas homelessness was inversely associated with prescription of DAAs (aOR 0.30, 95% CI 0.09-1.04, p = .057). Median time to receive a DAA script from date of diagnosis was seven days (IQR 0 to 14 days), and time to filling the DAA prescription was 2 days (IQR 0-12 days). In conclusion, provision of POC testing through NSPs was effective for linking new clients to HCV treatment and reduced the time to treatment. Further studies are needed to define the most cost-effective use of POC testing in models of care for people who inject drugs to increase HCV treatment uptake.

Impact of COVID-19 lockdown restrictions on hepatitis C testing in Australian primary care services providing care for people who inject drugs.

In 2020, the Australian state of Victoria experienced the longest COVID-19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de-identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time-series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C.

Latent Class Analysis of Sexual Behaviours and Attitudes to Sexually Transmitted Infections Among Gay and Bisexual Men Using PrEP.

Gay and bisexual men (GBM) who use pre-exposure prophylaxis (PrEP) are at increased risk of sexually transmitted infections (STIs) compared to those who don't use PrEP. Since the implementation of PrEP in Australia, it is possible that attitudes towards STIs have shifted in line with changes in risk and transmission dynamics in the context of increased screening. As the extent to which GBM utilise STI prevention strategies likely depends on their attitudes towards STIs and STI prevention, the aims of this study were to use latent class analysis (LCA) to classify GBM using PrEP on the basis of their attitudes towards STIs and reported risk behaviours, and examine how these categorisations relate to risk of STI acquisition. 1225 GBM who were previously enrolled in a PrEP implementation study (The PrEPX Study) completed a survey focused on sexual behaviours and attitudes towards STIs 1 year post-study follow-up. Data on chlamydia, gonorrhoea and syphilis testing and positivity were available through a sentinel network of participating study clinics. Using LCA, participants were allocated into four classes; Class 1, "Some concern and lowest risk"; Class 2, "Low concern and lower risk"; Class 3, " High concern and higher risk"; and Class 4, "Low concern and highest risk". The majority (78%) of participants were classified into Class 3 or Class 4, two groups which were distinguished by highly disparate attitudes towards STIs but with a similar proportion of participants diagnosed with a bacterial STI in the last 12 months (48% and 57%, respectively). Findings suggest that attitudes towards STIs among GBM using PrEP in Australia vary considerably, and this will likely influence their receptivity to different STI prevention strategies.

Microelimination of Hepatitis C Among People With Human Immunodeficiency Virus Coinfection: Declining Incidence and Prevalence Accompanying a Multicenter Treatment Scale-up Trial.

BACKGROUND: Gay and bisexual men (GBM) are a key population affected by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We aimed to measure HCV treatment effectiveness and to determine the population impact of treatment scale-up on HCV prevalence and incidence longitudinally among GBM. METHODS: The co-EC Study (Enhancing Care and Treatment Among HCV/HIV Coinfected Individuals to Eliminate Hepatitis C Transmission) was an implementation trial providing HCV direct-acting antiviral treatment in Melbourne, Australia, during 2016-2018. Individuals with HCV/HIV coinfection were prospectively enrolled from primary and tertiary care services. HCV viremic prevalence and HCV antibody/viremic incidence were measured using a statewide, linked, surveillance system. RESULTS: Among 200 participants recruited, 186 initiated treatment during the study period. Sustained virological response in primary care (98% [95% confidence interval {CI}, 93%-100%]) was not different to tertiary care (98% [95% CI, 86%-100%]). From 2012 to 2019, between 2434 and 3476 GBM with HIV infection attended our primary care sites annually, providing 13 801 person-years of follow-up; 50%-60% received an HCV test annually, and 10%-14% were anti-HCV positive. Among those anti-HCV positive, viremic prevalence declined 83% during the study (54% in 2016 to 9% in 2019). HCV incidence decreased 25% annually from 1.7/100 person-years in 2012 to 0.5/100 person-years in 2019 (incidence rate ratio, 0.75 [95% CI, .68-.83]; P < .001). CONCLUSIONS: High treatment effectiveness by nonspecialists demonstrates the feasibility of treatment scale-up in this population. Substantial declines in HCV incidence and prevalence among GBM provides proof-of-concept for HCV microelimination. CLINICAL TRIALS REGISTRATION: NCT02786758.

Real-world monitoring progress towards the elimination of hepatitis C virus in Australia using sentinel surveillance of primary care clinics; an ecological study of hepatitis C virus antibody tests from 2009 to 2019.

To achieve the elimination of the hepatitis C virus (HCV), sustained and sufficient levels of HCV testing is critical. The purpose of this study was to assess trends in testing and evaluate the effectiveness of strategies to diagnose people living with HCV. Data were from 12 primary care clinics in Victoria, Australia, that provide targeted services to people who inject drugs (PWID), alongside general health care. This ecological study spanned 2009-2019 and included analyses of trends in annual numbers of HCV antibody tests among individuals with no previous positive HCV antibody test recorded and annual test yield (positive HCV antibody tests/all HCV antibody tests). Generalised linear models estimated the association between count outcomes (HCV antibody tests and positive HCV antibody tests) and time, and χ2 test assessed the trend in test yield. A total of 44 889 HCV antibody tests were conducted 2009-2019; test numbers increased 6% annually on average [95% confidence interval (CI) 4-9]. Test yield declined from 2009 (21%) to 2019 (9%) (χ2P = <0.01). In more recent years (2013-2019) annual test yield remained relatively stable. Modest increases in HCV antibody testing and stable but high test yield within clinics delivering services to PWID highlights testing strategies are resulting in people are being diagnosed however further increases in the testing of people at risk of HCV or living with HCV may be needed to reach Australia's HCV elimination goals.

The Potential Impact of a Gel-Based Point-of-Sex Intervention in Reducing Gonorrhea Incidence Among Gay and Bisexual Men: A Modeling Study.

BACKGROUND: Increases in sexually transmitted infections among gay and bisexual men (GBM) over the past decade have coincided with declines in condom use and rapid uptake of HIV preexposure prophylaxis (PrEP). We explored the impact of an antimicrobial gel-based point-of-sex intervention (gel-PSI) with a lower efficacy for reducing gonorrhea transmission risk than condoms on population-level gonorrhea incidence among GBM in Victoria, Australia. METHODS: A deterministic compartmental model of HIV and gonorrhea transmission was used to project annual gonorrhea incidence from 2020 to 2025. Individuals were classified as HIV-negative (PrEP or non-PrEP users) or HIV-positive, and further stratified by gonorrhoea risk (high/low). All possible scenarios where between 0% and 100% of GBM using condoms transitioned to gel-PSI (considered a downgrade in protection) and 0% and 100% of GBM not using condoms transitioned to gel-PSI (considered an upgrade in protection), with gel-PSI efficacy ranging from 20% to 50%, were run. RESULTS: The baseline scenario of no gel-PSI uptake (status quo) projected 94,367 gonorrhea infections between 2020 and 2025, with an exponentially increasing trend in annual infections. For a gel-PSI efficacy of 30%, a net reduction in cumulative gonorrhea incidence was projected, relative to the status quo, for any ratio of proportion of condom users "downgrading" to proportion of noncondom users "upgrading" to gel-PSI use of less than 2.6. Under the supposition of equal proportions of condom users and noncondom users switching to gel-PSI, a relative reduction was projected for any gel-PSI efficacy greater than 16%. CONCLUSIONS: Our model suggests that the introduction of a gel-PSI could have benefits for controlling gonorrhea transmission among GBM, even in scenarios where the gel-PSI is considerably less efficacious than condoms and when gel-PSI uptake leads to consequent reductions in consistent condom use.

Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection.

Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP). Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement. Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018. Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring. Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378). Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]). Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Effects of Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection on Sexual Risk Behavior in Men Who Have Sex With Men: A Systematic Review and Meta-analysis.

Background: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However, concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM. Methods: We conducted a systematic review of open-label studies published to August 2017 that reported sexual risk outcomes in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis, and a qualitative review and risk of bias assessment were performed. Results: Sixteen observational studies and 1 open-label trial met selection criteria. Eight studies with a total of 4388 participants reported STI prevalence, and 13 studies with a total of 5008 participants reported change in condom use. Pre-exposure prophylaxis use was associated with a significant increase in rectal chlamydia (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.13) and an increase in any STI diagnosis (OR, 1.24; 95% CI, .99-1.54). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users. Conclusion: Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies.

Physical and mental health of long-term users of HIV preexposure prophylaxis in Australia.

INTRODUCTION: HIV preexposure prophylaxis (PrEP) is highly effective at preventing HIV. We aimed to assess mental and physical health among long-term PrEP users in Australia's X-PLORE cohort. METHODS: In early 2021, 1485 X-PLORE participants were emailed a survey covering demographics, sexual practices, ongoing PrEP use, physical and psychological diagnoses received since commencing PrEP, substance use, and impacts of the COVID-19 pandemic. Current anxiety and depression were assessed using GAD-7 and PHQ-9 questionnaires. RESULTS: Of 476 participants (completion rate 32.1%), 99.8% were cis-gender men. Median PrEP use duration was 48 months (2002 person-years), with 81.7% currently using PrEP. PrEP-related toxicity was uncommon: 2.9% reported bone fractures, 1.3% low bone density, and 4.0% reported kidney problems, largely not necessitating PrEP cessation. Most (92.0%) rated their health as 'good' to 'excellent', and 22.6% reported improved health since starting PrEP, often because of improved mental health. Only 6.2% reported deterioration in health since starting PrEP, largely unrelated to PrEP. The most common diagnoses were hypertension (9.9%), depression (13.2%) and anxiety (14.9%); 17% had PHQ-9 scores indicating current moderate-to-severe depression, which was associated with unemployment [adjusted odds ratio (aOR) 3.90], regular cannabis use (aOR 2.49), and having ceased PrEP (aOR 2.13). CONCLUSION: Among long-term PrEP users, of which over 80% were currently using PrEP, self-reported PrEP toxicity was uncommon. With almost one in five PrEP users categorized as having depression, and with higher risk among those having ceased PrEP, we recommend routine screening for depression and anxiety in PrEP users and corresponding follow-up of patients no longer attending for PrEP.

HIV incidence in people receiving government-subsidised pre-exposure prophylaxis in Australia: a whole-of-population retrospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective and has been government subsidised in Australia since April, 2018. We examined HIV incidence over 5 years in a retrospective observational cohort of people who had received subsidised PrEP. METHODS: Linked de-identified dispensing records for all government-subsidised oral PrEP, HIV antiretroviral therapy (ART), and hepatitis C treatment were used. We included all people dispensed subsidised PrEP from April 1, 2018, to March 31, 2023, and examined records up to Sept 30, 2023. Exposure was measured from date of first PrEP prescription and days covered by PrEP calculated for individuals based on quantity and date supplied. Assuming that HIV was diagnosed 30 days before ART initiation, we imputed the date of acquisition as the midpoint between the diagnosis and the later of the last PrEP prescription or 6 months before the diagnosis. We calculated HIV incidence and its predictors using Poisson regression. FINDINGS: We included 66 206 people dispensed PrEP: 64 757 (97·8%) were men; median age was 33 years (IQR 27-43). 207 people acquired HIV, with an overall incidence of 1·07 per 1000 person-years (95% CI 0·93-1·23). Incidence was 2·61 per 1000 person-years among those dispensed PrEP once only. Using this group as a comparator, those with 60% or more days covered by PrEP had a 78·5% reduction in incidence (0·56 per 1000 person-years, p<0·0001) and those with less than 60% days covered had a 61·6% reduction (0·99 per 1000 person-years, p=0·0045). Independent predictors of HIV acquisition were a record of hepatitis C treatment (9·83 per 1000 person-years, adjusted incident rate ratio [aIRR] 8·70, 95% CI 4·86-15·56), only attending prescribers outside of areas with a high estimated prevalence of gay men (1·66 per 1000 person-years, aIRR 1·50, 1·08-2·09), age 18-29 years (1·33 per 1000 person-years, aIRR 1·56, 1·11-2·21), and earlier year of first PrEP. INTERPRETATION: The low observed incidence of HIV among people receiving government-subsidised PrEP highlights the success of a national programme of oral PrEP scale-up in achieving sustained reduction in community HIV transmission. However, incidence varied greatly, indicating that more research is needed to understand why people were not taking PrEP at times of risk and emphasising the need for new interventions focused on this population to achieve elimination of HIV transmission. Individuals dispensed PrEP once only and less frequent users might benefit from more support. FUNDING: None.

Viral hepatitis testing and treatment in community pharmacies: a systematic review and meta-analysis.

Background: The World Health Organization seeks to eliminate viral hepatitis as a public health threat by 2030. This review and meta-analysis aims to evaluate the effectiveness of programs for hepatitis B and C testing and treatment in community pharmacies. Methods: Medline, Embase, Cochrane CENTRAL, and Global Health were searched from database inception until 12 November 2023. Comparative and single arm intervention studies were eligible for inclusion if they assessed delivery of any of the following interventions for hepatitis B or C in pharmacies: (1) pre-testing risk assessment, (2) testing, (3) pre-treatment assessment or (4) treatment. Primary outcomes were proportions testing positive and reaching each stage in the cascade. Random effects meta-analysis was used to estimate pooled proportions stratified by recruitment strategy and setting where possible; other results were synthesised narratively. This study was pre-registered (PROSPERO: CRD42022324218). Findings: Twenty-seven studies (4 comparative, 23 single arm) were included, of which 26 reported hepatitis C outcomes and four reported hepatitis B outcomes. History of injecting drug use was the most identified risk factor from pre-testing risk assessments. The pooled proportion hepatitis C antibody positive from of 19 studies testing 5096 participants was 16.6% (95% CI 11.0%-23.0%; heterogeneity I2 = 96.6%). The pooled proportion antibody positive was significantly higher when testing targeted people with specified risk factors (32.5%, 95% CI 24.8%-40.6%; heterogeneity I2 = 82.4%) compared with non-targeted or other recruitment methods 4.0% (95% CI 2.1%-6.5%; heterogeneity I2 = 83.5%). Meta-analysis of 14 studies with 813 participants eligible for pre-treatment assessment showed pooled attendance rates were significantly higher in pharmacies (92.7%, 95% CI 79.1%-99.9%; heterogeneity I2 = 72.4%) compared with referral to non-pharmacy settings (53.5%, 95% CI 36.5%-70.1%; heterogeneity I2 = 92.3%). The pooled proportion initiating treatment was 85.6% (95% CI 74.8%-94.3%; heterogeneity I2 = 75.1%). This did not differ significantly between pharmacy and non-pharmacy settings. Interpretation: These findings add pharmacies to the growing evidence supporting community-based testing and treatment for hepatitis C. Few comparative studies and high degrees of statistical heterogeneity were important limitations. Hepatitis B care in pharmacies presents an opportunity for future research. Funding: None.

Risk of Primary Incident Hepatitis C Infection Following Bacterial Sexually Transmissible Infections Among Gay and Bisexual Men in Australia From 2016 to 2020.

Background: In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Methods: Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Results: Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11-3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42-5.32]) and rectal gonorrhea (2.54 [1.28-5.05]) diagnoses were associated with incident HCV. Conclusions: Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP.

Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022.

Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83-2.14), living with HIV (aHR = 1.83, 95% CI = 1.12-1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61-1.97) were associated with syphilis diagnosis. Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council.

Prioritising the values of potential users to promote uptake of HIV pre-exposure prophylaxis.

Benefits of pre-exposure prophylaxis (PrEP) extend beyond HIV risk reduction. Users report a range of physical, emotional, and social effects, including reduced anxiety, increased intimacy, and greater sexual satisfaction. For some people, these benefits are the primary motivation for using PrEP. To successfully engage in shared decision making about HIV prevention methods, clinicians need to be able to discuss all potential risks and benefits of PrEP. These risks and benefits include not only those related to HIV risk reduction and other clinical outcomes, but also those related to experiences and relationships that people value. However, national and international clinical resources on the provision of PrEP do not include user-reported outcomes that are values-based or reflect positive effects on personal, social, or sexual wellbeing. To better integrate the values of potential users into discussions about PrEP, clinician training programmes and clinical guidelines need to be guided by community-driven frameworks and expanded to include user-reported outcomes of PrEP use, including beneficial effects. Achieving PrEP uptake and equity goals will require an approach to PrEP provision that centres the values and desired experiences of potential users, particularly those from populations with the greatest unmet need for PrEP.