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Introduction: Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis. We aimed to identify barriers and missed opportunities in PrEP uptake, care and use among MSM with HIV and previous PrEP experience., Methods: Between March 2022-March 2023, we conducted semi-structured in-depth interviews on PrEP among MSM diagnosed with HIV from 2019 onwards with previous PrEP experience. Interviewees were recruited through their HIV treatment centers and social media., Results: Of the 11 included MSM, most reported significant PrEP-uptake delay because of the limited NPP capacity and high threshold of accessing PrEP from GPs (e.g. stigma, lack of sexual health expertise). Additional uptake or use barriers included anticipated/experienced side-effects, burden of daily pill-taking or event-driven regimen complexity, the latter leading to PrEP discontinuation. Missed opportunities in counseling on adherence and safer sex alternatives after discontinuation were reported. Most interviewees considered informal PrEP unsuitable., Conclusion: PrEP uptake delay played a crucial role in context of HIV infection among MSM with HIV and previous PrEP experience. HIV diagnoses at or shortly after PrEP initiation emphasize the importance of ensuring rapid and timely PrEP access. Uptake barriers at GPs, stigma on sexuality, lack of expertise, and missed care opportunities need to be addressed. Early detection of PrEP protocol/user-mismatch and counseling on safer sex alternatives after discontinuation are pivotal for sustainable HIV prevention., Competing Interests: MP obtained unrestricted research grants and speaker/advisory fees from Gilead Sciences, Abbie and MSD; all of which were paid to her institute and were unrelated to the current work. UD obtained unrestricted research grants and speaker fees from Gilead Science; this was paid to his institution and was unrelated to the current work. No potential conflicts of interests were reported by the remaining authors. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Koole et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Little is known about the effect of hepatitis C virus (HCV) treatment on sexual risk behavior among men who have sex with men (MSM) with HIV by treatment type (interferon [IFN]-based vs direct-acting antiviral [DAA]-based)., Setting: MSM with HIV and recently acquired HCV infection enrolled in the MSM Observational Study of Acute Infection with hepatitis C (MOSAIC) cohort., Methods: Using data from 2009 to 2018, we evaluated risk behavior through a validated HCV risk score (where ≥2 indicated high risk) and its individual risk behaviors. Levels of risk behavior before, during, and after treatment were modeled for each treatment episode using linear and logistic regression with Generalized Estimating Equations adjusting for DAA availability and number of reinfections., Results: One hundred forty MSM with a median age of 45 years (interquartile range = 40-49) yielded 180 treatment episodes (n = 131 IFN-based, n = 49 DAA-based). Adjusted mean risk score before, during, and after treatment was 2.4 (95% confidence interval [CI] = 2.1 to 2.6), 0.9 (95% CI = 0.8 to 1.0), and 1.7 (95% CI = 1.5 to 1.8), respectively. Before treatment, no differences in mean HCV risk score or proportion of specific behaviors were found between the regimen groups. During treatment, MSM treated with DAAs had a higher average risk score and proportion of receptive condomless anal sex, sharing toys and unprotected fisting than those treated with IFN. After treatment, the proportion sharing straws were significantly higher in MSM treated with DAAs than in MSM treated with IFN., Conclusions: MSM treated with DAAs, compared with MSM treated with IFN, had higher levels of HCV-related risk behavior during treatment. The higher risk of HCV reinfection in the DAA-era underscores the need for ongoing HCV testing and behavioral interventions against HCV., Competing Interests: J.S.'s institution has received research support and consultancy fees from Gilead, and a speakers fee from Janssen Pharmaceuticals, independent from the submitted work. M.P.'s institution has received speakers fees and independent scientific support from Gilead Sciences, Roche, MSD, and Abbvie, outside the submitted work. M.V.'s institution has received consultancy fees from Gilead, MSD, and ViiV outside the submitted work and research grants from Gilead, Merck Sharp Dome, and ViiV. K.B. has served on (inter)national advisory boards for Gilead, ViiV, Janssen, and MSD outside the submitted work. A.B. has received speaker fees from Gilead, independent from the submitted work. B.R. has received grants from MSD and Gilead Sciences, and participated in advisory boards and received travel support from MSD, Janssen-Cilag, Bristol-Myers Squibb, Gilead Sciences, Pfizer, and ViiV Healthcare, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The Dutch HIV preexposure prophylaxis (PrEP) pilot provided subsidized PrEP care to maximum 2900 individuals at a time in Amsterdam. Populations with expected barriers to accessing PrEP elsewhere were prioritized for program inclusion. We evaluated their prior sexual health service engagement and PrEP need., Design: Cross-sectional analysis using enrolment data., Methods: We included individuals ever enrolled in the PrEP program at the Center for Sexual Health (CSH) Amsterdam between 2019 and 2023. We calculated the proportion belonging to higher-priority groups (i.e., <25 years old, transgender, sex worker, uninsured or migrant). We defined classes of sexual health service engagement in the 12 months preceding enrolment using latent class analysis (LCA). We compared engagement classes, sexual behavior and positivity of HIV and sexually transmitted infections (STI) between higher- and lower-priority groups., Results: 2004/4075 (49%) individuals enrolled belonged to higher-priority groups. LCA showed three classes of prior engagement: "newly engaged" (14%, n  = 551) were new to the CSH-Amsterdam; "PrEP initiators" (40%, n  = 1642) previously visited the CSH-Amsterdam but had not used PrEP; "PrEP experienced" individuals (46%, n  = 1882) previously accessed PrEP. Higher-priority groups were more often "newly engaged" or "PrEP-initiators" than "PrEP-experienced". Higher-priority groups less often had condomless anal sex with casual partners or chemsex in the prior 6 months. Positivity of bacterial STI was similar between higher-priority ( n  = 300/2004, 15.0%) and lower-priority ( n  = 315/2071, 15.2%) groups. 13/14 HIV diagnoses at enrolment were in higher-priority groups., Conclusion: Higher-priority populations had less often previously used sexual health services and accounted for most new HIV diagnoses at enrolment. Engaging these populations in sexual healthcare, including PrEP, should be stressed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Historically, hepatitis C virus (HCV) was difficult to treat among people with HIV. However, treatment with direct-acting antivirals (DAAs) results in 90%-95% of people being cured. There is a need to understand why a proportion of people are not cured. We aimed to examine characteristics that may indicate an increased probability of unsuccessful DAA HCV treatment., Methods: Data were from the International Collaboration on Hepatitis C Elimination in HIV Cohorts. People who commenced DAA HCV treatment between 2014 and 2019 were included. Unsuccessful treatment was defined as a positive HCV RNA test at a person's first RNA test at least 4 weeks (SVR4+) following the end of treatment. Multivariable mixed-effects logistic regression was used to examine characteristics associated with unsuccessful treatment., Results: Of 4468 people who commenced DAA treatment, 4098 (91.7%) had an SVR test 4+ weeks following the end of treatment, 207 (5%) of whom were unsuccessfully treated. Compared to a CD4+ cell count > 500 cells/mm 3 , cell counts < 200 (aOR 1.81, 95%CI 1.00-3.29) and between 200 and 349 (aOR 1.95, 95%CI 1.30-2.93) were associated with increased odds of unsuccessful treatment. Among 1921 people with data on injection drug use in the 12 months prior to treatment, there was some evidence that recent injection drug use was associated with increased odds of unsuccessful treatment; however, this was not statistically significant (aOR 1.67, 95%CI 0.99-2.82)., Conclusions: The overwhelming majority of people were successfully treated for HCV. Overall, 5% of those with an SVR4+ test were unsuccessfully treated; this was more likely among people with evidence of immunodeficiency and those who reported recently injecting drugs., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Objective: HIV can be effectively prevented by oral HIV pre-exposure prophylaxis (PrEP). When PrEP was introduced, there was apprehension that condom use would decrease and STIs would increase. The purpose of this study was to investigate sexual behaviour and STI incidence among PrEP users., Design: Prospective cohort study METHODS: The Amsterdam PrEP demonstration project (AMPrEP) provided oral PrEP to men who have sex with men (MSM) and transgender women from 2015 to 2020. Participants could choose between daily and event-driven PrEP. We tested for HIV and STIs at each quarterly study visit. We examined changes in numbers of sex partners and frequency of condomless anal sex with casual partners (CAS) with negative binomial regression. We examined HIV incidence, and changes in STI incidence using Poisson regression., Results: 367 participants (365 MSM) initiated PrEP, median duration of participation was 3.9 years (interquartile range[IQR]=3.4-4.0). Median number of sex partners per three months was 13 (IQR=6-26) and decreased with each additional year on PrEP (adjusted rate ratio[aRR]=0.86/year, 95%confidence interval[CI]=0.83-0.88). Frequency of CAS per three months was 10 (IQR=3-20.5) and also decreased (aRR=0.92/year, 95%CI=0.88-0.97). Incidence of any STI was 87/100PY (95%CI=82-92) and did not increase over time. Two HIV infections were diagnosed (incidence=0.2/100PY; 95%CI=0.0-0.6), both during the first year and among daily PrEP users., Conclusions: In this prospective cohort with an observation period of four years, we observed a low HIV incidence and a decrease in the number of sex partners and CAS over time. Although STI incidence was high, it did not increase.

Competing Interests: Declaration of interests JMZ has received consulting fees from Gilead Sciences and Merck & Co. JA has received consulting fees from Gilead Sciences; honoraria from Gilead Sciences and ViiV Healthcare; travel support from Gilead Sciences and ViiV Healthcare; book royalties from Elsevier Royalties; and has served on a Data Safety and Monitoring Board for the RIO HIV Trial. DDD has received consulting fees from Gilead Sciences and honoraria from Gilead Sciences and ViiV Healthcare. VDL has received research grants from the Canadian Foundation for AIDS Research and Canadian Institutes of Health Research and an honorarium from ViiV Healthcare. AC has received a research grant from Gilead Sciences. ND has received an honorarium from ViiV Healthcare. CD has received consulting fees from WHO. SH has received consulting fees from the BCG Boston Consulting Group. JVL has received consulting fees from Echosens, GlaxoSmithKline, Novo Nordisk, NovoVax, and Pfizer; honoraria from AbbVie, Echosens, Gilead Sciences, Janssen Therapeutics, Moderna, Merck Sharp & Dohme, Novo Nordisk, Pfizer; and has served on a Data Safety and Monitoring Board for the QuickStart Study. KM has received research grants and consulting fees from Gilead Sciences, Merck & Co, and ViiV Healthcare. MM has received consulting fees from Janssen Therapeutics. SRa has received an honorarium from the AIDS Healthcare Foundation. All other authors declare no competing interests.

Introduction: Transgender women are at increased risk of acquiring HIV. Earlier studies reported lower retention in HIV care, antiretroviral therapy uptake, adherence and viral suppression. We assessed the stages of the HIV care continuum of transgender women in the Netherlands over an 11-year period. In addition, we assessed new HIV diagnoses and late presentation, as well as disengagement from care, between 2011 and 2021., Methods: Using data from the Dutch national ATHENA cohort, we separately assessed viral suppression, as well as time to achieving viral suppression, among transgender women for each year between 2011 and 2021. We also assessed trends in new HIV diagnoses and late presentation (CD4 count of <350 cells/µl and/or AIDS at diagnosis), and disengagement from care., Results: Between 2011 and 2021, a total of 260 transgender women attended at least one HIV clinical visit. Across all years, <90% of transgender women were virally suppressed (207/239 [87%] in 2021). The number of new HIV diagnoses fluctuated for transgender women (p trend = 0.053) and late presentation was common (ranging between 10% and 67% of new HIV diagnoses). Of the 260 transgender women, 26 (10%) disengaged from care between 2011 and 2021 (incidence rate = 1.10 per 100 person-years, 95% confidence interval = 0.75-1.61)., Conclusions: Between 2011 and 2021, less than 90% of transgender women linked to HIV care were virally suppressed. Late presentation at the time of diagnosis and disengagement from care were common. Efforts are needed to identify barriers to early HIV diagnosis and to optimize the different steps across the care continuum for transgender women., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Objective: We assessed the association and concordance between self-reported oral pre-exposure prophylaxis (PrEP) intake in a diary app and intraerythrocytic drug metabolite concentrations., Design: AMPrEP was a prospective demonstration study providing daily and event-driven PrEP to MSM in Amsterdam, the Netherlands (2015-2020)., Methods: Participants could record their PrEP intake in a diary app. Dried blood spots (DBS) were taken at 6, 12, 24, and 48 months and analysed for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations. We included TFV-DP measurements preceded by diary completion on at least 90% of days in the 6 weeks prior. We examined the association between self-reported PrEP intake (i.e. number of pills) and TFV-DP concentrations using tobit regression with a random intercept per participant. We also calculated concordance between categorized PrEP intake (i.e. <2, 2-3, 4-6 or 7 pills per week) and categorized TFV-DP concentrations (i.e. <350, 350-699,700-1249 or ≥1250 fmol/punch) using weighted Cohen's kappa. Last, we calculated concordance between self-reported recent PrEP intake (yes/no, in past 2 days) and quantifiability of FTC-TP (yes/no) using Cohen's kappa., Results: Seven hundred and fifty-nine DBS measurements from 282 MSM were included. Self-reported PrEP intake was strongly and positively associated with TFV-DP concentration ( β  = 0.77, 95% CI = 0.70-0.84, P  < 0.0001). Concordance between categorized PrEP intake and TFV-DP concentration was moderate ( κ  = 0.44, 95% CI = 0.39-0.50). Concordance between self-reported recent PrEP intake and FTC-TP quantifiability was perfect ( κ  = 0.83, 95% CI 0.76-0.90)., Conclusion: Self-reported PrEP intake in a diary app is strongly correlated with actual use, and therefore reliable for comparing PrEP adherence between groups. Still, suboptimal criterion validity according to clinically relevant categories warrants caution when assessing 6-week reported adherence for individuals., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection., Methods: We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year., Findings: Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019., Interpretation: HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead; consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work; and is supported by a Tier I Canada Research Chair. AR reports support to his institution for advisory boards or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator initiated trial grant from Gilead Sciences; all remuneration to AR was paid to his home institution, and all remuneration was provided outside the submitted work. KL reports honoraria for advice or public speaking from Gilead, MSD, and ViiV Healthcare; support for attending meetings or travel expenses from Gilead and MSD; and a leadership or fiduciary role in other board, society, committee or advocacy groups, paid or unpaid, from Spikmm. FB reports grants from Gilead and honoraria from Gilead, ViiV Healthcare, and MSD. NKM received research grants from Gilead and the US National Institutes of Health unrelated to this work. TS reports consulting fees from Biogen for serving on advisory boards and scientific leadership committees. JSD reports investigator-initiated research funding to his institution from Gilead Sciences; investigator-initiated and company sponsored research funding to his institution from AbbVie; and consulting fees unrelated to this work to his institution from AbbVie. GVM reports grants or contracts from Gilead, AbbVie, ViiV Healthcare, and Janssen to her institution; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events; and support for attending meetings or travel expenses from Gilead; and participation on a data safety monitoring board or advisory board for Gilead, ViiV Healthcare, and AstraZeneca. IJ reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Gilead Sciences, ViiV Healthcare, and GESIDA; and payment for expert testimony and support for attending meetings or travel expenses from Gilead Sciences. AB reports speakers fees from Gilead Sciences; and participation on a data safety monitoring board for Amsterdam University Medical Centers and an advisory board for ANRS Emerging Infectious Diseases. MvdV reports grants or contracts and consulting fees from Gilead, ViiV Healthcare, and MSD to his institution. MH reports investigator-initiated research grants from Gilead Sciences and AbbVie. MS reports investigator-initiated research grants from Gilead Sciences and AbbVie. M-BR reports funding from SIDACTION for the duration of her PhD. RG reports funding from Cepheid and SpeeDex towards the Australian Research Council Industrial Transformation Research Program Hub to Combat Antimicrobial Resistance grant (IH190100021). Cepheid has also contributed in-kind study equipment (cartridges, machines) to the project Scaling up infectious disease point-of-care testing for Indigenous people (RARUR000080) funded by the Medical Research Future Fund Rapid Applied Research Translation grant. RS-D, DKvS, CS, OL, MP, LW, JY, AS, and JB declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants., Methods: We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability., Results: Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm 3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61])., Conclusion: Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era., Competing Interests: Declaration of competing interest Juan Berenguer reports honoraria for advice and public speaking from ABBVIE, GILEAD, MSD, JANSSEN, and ViiV Healthcare, as well as grants from ABBVIE, GILEAD, MSD, and ViiV Healthcare. Marina Klein reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead, and consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work. Marina Klein is supported by a Tier I Canada Research Chair. Andri Rauch reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator-initiated trial (IIT) grant from Gilead Sciences. All remuneration to Andri Rauch went to his home institution and not to Andri Rauch personally; furthermore this remuneration was provided outside the submitted work. Karine Lacombe reports honoraria for advice and public speaking from Abbvie, Gilead, MSD, Janssen and ViiH Healthcare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Studies have shown varying trends in incidence of sexually transmitted infections (STIs) among individuals using HIV pre-exposure prophylaxis (PrEP). Characterization of individuals at increased risk for STIs may offer an opportunity for targeted STI screening., Design: Group-based trajectory modeling., Methods: We screened participants from the AMPrEP demonstration project (2015-2020) for urogenital, anal, and pharyngeal chlamydia and gonorrhea, and syphilis every 3 months and when needed. We identified trajectories of STI incidence within individuals over time and determinants of belonging to a trajectory group. We calculated cumulative proportions of STIs within STI trajectory groups., Results: Three hundred and sixty-six participants with baseline and at least one screening visit during follow-up were included (median follow-up time = 3.7 years [interquartile range, IQR = 3.5-3.7]). We identified three trajectories of STI incidence: participants with a mean of approximately 0.1 STIs per 3 months ('low overall', 52% of the population), participants with a mean 0.4 STI per 3 months ('medium overall', 43%), and participants with high and fluctuating (between 0.3 and 1 STIs per 3 months) STI incidence ('high and fluctuating', 5%). Participants in the 'low overall' trajectory were significantly older, and reported less chemsex and condomless anal sex with casual partners than participants in the other trajectories. Participants in the 'high and fluctuating' and 'medium overall' groups accounted for respectively 23 and 64% of all STIs observed during follow-up., Conclusions: STI incidence was concentrated in subpopulations of PrEP users who were younger, had more chemsex and condomless anal sex. Screening frequency for STIs could be reduced for subpopulations with low risk for incident STIs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe., Design, Setting and Participants: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months)., Measurements: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID., Findings: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity., Conclusions: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration., (© 2023 Society for the Study of Addiction.)

Background: In May 2022, an outbreak of mpox (monkeypox) in men-who-have-sex-with-men (MSM) emerged and quickly affected over 100 countries. In the early stages of the outbreak, overlap in symptoms with sexually transmitted infections (STI) made triage for mpox testing challenging. More information was needed on whom to screen and the main route of transmission., Objectives: We aimed to identify characteristics of mpox cases to further strengthen case definitions. We also compared Cycle threshold (Ct) values of the DNA positive mpox samples as a proxy for viral load by body location., Methods: From 20 May 2022 to 15 September 2022, we tested all MSM who presented with malaise, and/or ulcerative lesions, and/or proctitis and/or a papular-vesicular-pustular eruption attending the Centre of Sexual Health in Amsterdam, the Netherlands, for mpox, with a PCR test. In the same period, 6932 MSM mpox unsuspected clients were not tested. We compared those tested positive for mpox with those tested negative and those unsuspected for mpox., Results: Of the 374 MSM tested, 135 (36%) were positive for mpox. The mpox-positive MSM were older (median age, respectively, 36, 34 and 34 years, p = 0.019) and more often lived with HIV (30% vs. 16% and 7%, p < 0.001). Furthermore, mpox-positive patients more often reported receptive anal sex without a condom, sexualized drug use, more sex partners, and were more often diagnosed with bacterial STI (p < 0.001). Systemic symptoms and anogenital lesions were associated with mpox infection. For mpox-positive patients, anal samples (p = 0.009) and lesional samples (p = 0.006) showed significantly lower median mpox Ct values compared to throat samples., Conclusions: Mpox-positive patients more often reported receptive anal sex without a condom, had more sex partners and more often lived with HIV. Our results suggest that in the current mpox outbreak among MSM, sexual transmission is the main route., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objectives: Adherence is key to the effectiveness of oral pre-exposure prophylaxis (PrEP) to prevent HIV. Therefore, we aimed to explore factors associated with adherence to daily PrEP (dPrEP)., Methods: Men who have sex with men (MSM) using dPrEP (emtricitabine/tenofovir disoproxil) within the Amsterdam PrEP demonstration project at the Public Health Service of Amsterdam, provided dried blood spots (DBS) 12 and 24 months after PrEP initiation. From DBS, we determined intracellular tenofovir diphosphate (TFV-DP) concentrations to assess adherence; TFV-DP ≥700 fmol/punch was considered adequate. We assessed associations of sociodemographic, clinical and behavioural characteristics with TFV-DP concentrations using multivariable linear regression., Results: Of 263 participants who attended 12-month or 24-month study visits while on dPrEP, 257 (97.7%) provided DBS at one or both visits (492 DBS in total). Median TFV-DP concentration was 1299 (IQR 1021-1627) fmol/punch (12 months: 1332 (1087-1687); 24 months: 1248 (929-1590]). Higher TFV-DP concentrations were associated with: older age (p=0.0008), condomless anal sex with a casual partner in 6 months preceding PrEP initiation (+166 fmol/punch; 95% CI 36.5 to 296) and using a mobile application providing visualised feedback on PrEP use and sexual behaviour (+146 fmol/punch; 95% CI 28.1 to 263). Lower TFV-DP concentrations were associated with longer duration of PrEP use (24 vs 12 months; -91.5 fmol/punch; 95% CI -155 to -28.1). Time-updated number of sex partners, diagnosed STIs and chemsex were not associated with TFV-DP concentrations., Conclusions: Overall, TFV-DP concentrations were high among MSM using dPrEP, indicating excellent adherence. Especially older participants, those who reported condomless anal sex with a casual partner prior to PrEP initiation and those who used an app with visualised feedback showed higher levels of adherence. As TFV-DP concentrations had decreased slightly at 2 years of PrEP use when compared with 1 year, we emphasise the importance of adherence counselling to those who continue using PrEP., Trial Registration Number: NL5413., Competing Interests: Competing interests: The study medication was provided by Gilead Sciences based on unconditional grants. EH received advisory board fees from Gilead Sciences and speaker fees from Janssen‐Cilag, both paid to her institute. UD received unrestricted research grants and speaker’s fees from Gilead Sciences, paid to his institute. HJCdV received grants from Medigene, and advisory board and speaker fees from Gilead Sciences, Medigene, AbbVie, Janssen‐Cilag and Willpharma, paid to his institute. MP received unrestricted research grants and speaker’s fees from Gilead Sciences, Roche, AbbVie and MSD, paid to her institute. MSvdL served on an Advisory Board of MSD, paid to his institute. All other authors declared no competing interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Daily and event-driven oral pre-exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM)., Methods: Using data from a mobile, web-based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be-PrEP-ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event-driven oral PrEP every 3 months. We used group-based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories., Results: We included 516 MSM (n = 322 AMPrEP; n = 194 Be-PrEP-ared), of whom 24% chose event-driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow-up (median = 508 days [IQR = 429-511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week ("low frequency," 12% of the total population), 4 tablets per week ("variable," 17%), "almost daily" (31%) and "always daily" (41%). Compared to participants with "low frequency" PrEP use, participants with "variable" (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04-4.60) and "almost daily" PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27-5.49). "Almost daily" PrEP users were more often employed (OR = 6.76, 95% CI = 2.10-21.75) and were younger compared to participants with "low frequency" PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with "low frequency" PrEP use compared to the other groups (all p<0.001). Compared to "low frequency" PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with "almost daily" and "always daily" PrEP use., Conclusions: We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two-regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: The COVID-19 pandemic has widespread consequences for health facilities, social contacts, and health-seeking behaviour, affecting the incidence, diagnosis and reporting of other infectious diseases. We examined trends in reported chronic hepatitis C virus (HCV) infections and associated transmission routes in the Netherlands to identify the potential impact of COVID-19 on access to healthcare (testing) services., Methods: We analysed notification data of patients with chronic HCV reported to the National Notifiable Disease Surveillance System from January 2019 until December 2021 in the Netherlands. Rates of newly reported chronic cases per 100,000 population with 95% confidence intervals (CI) were calculated, and we compared proportional changes in transmission routes for chronic HCV between 2019, 2020 and 2021., Results: During the study period, a total of 1,521 chronic HCV infections were reported, 72% males, median age 52 years, and an overall rate of 8.8 (95%CI 8.4-9.2) per 100,000 population. We observed an overall decline (-41.9%) in the number of reported chronic HCV in 2020 compared to 2019, with the sharpest decline in men who have sex with men (MSM)-related transmission (-57.9% in 2020, p = 0.005)., Conclusions: Reported cases of chronic HCV strongly declined during the COVID-19 pandemic when healthcare services were scaled down. Between February and June 2021, reported chronic HCV cases increased again, indicating a recovery of healthcare services. MSM showed the largest decline compared to other groups. Further research is needed to fully understand the impact of access to healthcare, health seeking behaviour, and (sexual) transmission risks of HCV during the COVID-19 pandemic., (© 2023. The Author(s).)

Background and Aims: Although the Netherlands, Canada and Australia were early adopters of harm reduction for people who inject drugs (PWID), their respective HIV and hepatitis C (HCV) epidemics differ. We measured the pooled effect of needle and syringe program (NSP) and opioid agonist therapy (OAT) participation on HIV and HCV incidence in these settings., Design: For each cohort, we emulated the design and statistical analysis of a target trial using observational data., Setting and Participants: We included PWID at risk of HIV or HCV infection from the Amsterdam Cohort Studies (1985-2013), Vancouver Injection Drug Users Study (1997-2009) and Melbourne Injecting Drug User Cohort Study (SuperMIX) (2010-2021)., Measurements: Separately for each infection and cohort (only HCV in SuperMIX), marginal structural models were used to compare the effect of comprehensive (on OAT and 100% NSP coverage or on OAT only if no recent injection drug use) versus no/partial NSP/OAT (no OAT and/or <100% NSP coverage) participation. Pooled hazard ratios (HR) and 95% CI were calculated using random-effects meta-analysis., Findings: We observed 94 HIV seroconversions and 81 HCV seroconversions among 2023 and 430 participants, respectively. Comprehensive NSP/OAT led to a 41% lower risk of HIV acquisition (pooled HR = 0.59, 95% CI = 0.36-0.96) and a 76% lower risk of HCV acquisition (pooled HR = 0.24, 95% CI = 0.11-0.51), compared with no/partial NSP/OAT, with little heterogeneity between studies for both infections (I 2  = 0%)., Conclusions: In the Netherlands, Canada and Australia, comprehensive needle and syringe program and opioid agonist therapy participation appears to substantially reduce HIV and hepatitis C acquisition compared with no or partial needle and syringe program/opioid agonist therapy participation. These findings from an emulated trial design reinforce the critical role of comprehensive access to harm reduction in optimizing infection prevention for people who inject drugs., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission., Methods: Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model., Results: We included 366 participants. Median follow-up was 47 months (IQR 43-50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51))., Conclusion: Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low., Competing Interests: Competing interests: The Public Health Service of Amsterdam received the drugs for the Amsterdam PrEP Study from Gilead Sciences based on an unconditional grant. UD received unrestricted research grants and speaker fees from Gilead Sciences, paid to his institute. HdV received grants from Medigene, and advisory board and speaker fees from Gilead Sciences, Medigene, Abbvie, Janssen-Cilag and Willpharma, all paid to his institute. MP received unrestricted research grants and speaker fees from Gilead Sciences, Roche, Abbvie and MSD, all paid to her institute. All other authors declare no competing interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study identified subgroups of sexual behaviors associated with increased STI/HIV risk among those eligible for but not using pre-exposure prophylaxis (PrEP) in order to improve PrEP uptake and prioritization in the context of restricted capacity. We used data from sexual health centers (SHCs) in the Netherlands, including all visits of eligible but non-PrEP using men who have sex with men (MSM), men who have sex with men and women (MSMW) and transgender persons between July 2019 (start of the Dutch national PrEP pilot (NPP)) and June 2021. Using latent class analysis (LCA), we identified classes of sexual behaviors (number of partners, chemsex, group sex and sex work) and explored whether these classes were associated with STI diagnosis and sociodemographics. Across 45,582 visits of 14,588 eligible non-PrEP using individuals, the best fitting LCA model contained three classes of sexual behaviors. Classes were distinguished by seldomly reported sexual behaviors (class 1; 53.5%, n = 24,383), the highest proportions of ≥6 partners and group sex (class 2; 29.8%, n = 13,596), and the highest proportions of chemsex and sex work (class 3; 16.7% of visits, n = 7,603). Visits in classes 2 and 3 (vs. class 1) were significantly more often with individuals who were diagnosed with an STI, older (≥36 vs. ≤35 years), MSMW (vs. MSM), and visiting an urban (vs. non-urban) SHC; while these visits were significantly less often with individuals from an STI/HIV endemic area. The percentage of visits at which an STI was diagnosed was 17.07% (n = 4,163) in class 1, 19.53% (n = 2,655) in class 2 and 25.25% (n = 1,920) in class 3. The highest risk of STI, and thereby HIV, was in those engaging in specific subgroups of sexual behavior characterized by frequently reporting multiple partners, group sex, sex work or chemsex. PrEP uptake should be encouraged and prioritized for these individuals., Competing Interests: MP obtained unrestricted research grants and speaker/ advisory fees from Gilead Sciences, Abbvie and MSD; all of which were paid to her institute and were unrelated to the current work. EH obtained unrestricted research grants from Gilead Sciences, which were paid to her institute and were unrelated to the current work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors report no conflicts of interest., (Copyright: © 2023 de la Court et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM., Methods: The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate., Discussion: The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination., Trial Registration: ClinicalTrials.gov NCT04156945. Registered on November 8, 2019., (© 2023. The Author(s).)

Objectives: We studied the effects of restrictions related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic on the use of sexual healthcare and pre-exposure prophylaxis (PrEP) and on the incidence of sexually transmitted infections (STIs) among men who have sex with men (MSM) in a prospective, open-label PrEP demonstration study (AMPrEP) in Amsterdam, the Netherlands., Methods: We retrieved data from 2019 to 2020 for participants with one or more study visit in 2019 (n = 305) and from two COVID-19 questionnaires (2020: n = 203; 2021: n = 160). Analyses were stratified for three periods of pandemic-related restrictions (first: 15 March 2020-15 June 2020; second: 16 June 2020-15 September 2020; third: 16 September 2020-31 December 2020 or 1 April 2021 for the COVID-19 questionnaire). Endpoints included returning for care during the pandemic, PrEP use (increased/unchanged vs. deceased/stopped, relative to 2019), and any STI/HIV. We modelled determinants of care and PrEP use via multivariable logistic regression and STI incidence using piecewise Poisson regression, comparing the 2020 and 2019 periods., Results: Of the 305 MSM included in the analysis, 72.8% returned for care during the pandemic, and this was significantly more likely among daily (vs. event-driven) PrEP users (p < 0.001). Increased/unchanged PrEP use ranged from 55.2% to 58.1% across the three pandemic periods and was more likely among those reporting chemsex in the first (p = 0.001) and third (p = 0.020) periods and among those reporting an increased/unchanged number of sex partners during the second period (p = 0.010). STI incidence was significantly lower in 2020 than in 2019 during the first period (incidence rate ratio [IRR] 0.43; 95% confidence interval [CI] 0.28-0.68) and not significantly different during the second (IRR 1.38; 95% CI 0.95-2.00) and third (IRR 1.42; 95% CI 0.86-2.33) periods. No HIV was diagnosed., Conclusion: COVID-19-related restrictions coincided with reduced care and PrEP use. Changes in STI incidence suggest delayed diagnoses. Ways to ensure continued access to sexual healthcare during restrictions are needed., (© 2022 British HIV Association.)

Background: Microbiologic diagnosis of childhood tuberculosis may be difficult. Oral swab specimens are a potential noninvasive alternative to sputum specimens for diagnosis., Methods: This was a prospective diagnostic accuracy study of oral swab specimens (buccal and tongue) for pulmonary tuberculosis diagnosis in children (aged ≤ 15 years) in 2 South African hospital sites. Children with cough of any duration as well as a positive tuberculin skin test result, tuberculosis contact, loss of weight, or chest radiograph suggestive of pulmonary tuberculosis were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Xpert MTB/RIF Ultra) assay and liquid culture. Oral swab specimens were obtained before sputum specimens, frozen, and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed tuberculosis, unconfirmed tuberculosis (receipt of tuberculosis treatment), or unlikely tuberculosis according to National Institutes of Health consensus definitions based on sputum microbiologic results., Results: Among 291 participants (median age [interquartile range], 32 [14-73] months), 57 (20%) had human immunodeficiency virus (HIV), and 87 (30%) were malnourished; 90 (31%) had confirmed pulmonary tuberculosis (rifampicin resistant in 6 [7%] ), 157 (54%), unconfirmed pulmonary tuberculosis, and 44 (15%), unlikely tuberculosis. A single oral swab specimen was obtained from 126 (43%) of the participants (tongue in 96 and buccal in 30) and 2 swab specimens from 165 (57%) (tongue in 110 and buccal in 55). Sensitivity was low (22% [95% confidence interval, 15%-32%]) for all swab specimens combined (with confirmed pulmonary tuberculosis as reference), but specificity was high (100% [91%-100%]). The highest sensitivity was 33% (95% confidence interval, 15%-58%) among participants with HIV. The overall yield was 6.9% with 1 oral swab specimen and 7.2% with 2., Conclusions: Use of the Xpert MTB/RIF Ultra assay with oral swab specimens provides poor yield for microbiologic pulmonary tuberculosis confirmation in children., Competing Interests: Potential conflicts of interest. H. C. reports grants from the National Institutes of Health to the FEND-TB consortium and from the EDCTP (European and Developing Countries Clinical Trials Partnership) to the TB-CAPT consortium, both outside the scope of this work, and consulting fees from the UNOPS–Stop TB Partnership. M. P. N. reports unpaid participation on an advisory board for the TB Speed Consortium. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011-2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs ( n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0-17.0); PAF = 55.3% (95% CI 43.3-83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3-8.7); PAF = 38.0% (95% CI 18.3-93.6)) and anal STI (RR = 5.3 (95% CI 1.7-16.7); PAF = 22.0 (95% CI -16.8 to 100.0)) were significantly ( P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6-2.4); PAF = 19.5 (95% CI 10.6-30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0-3.0); PAF = 28.0 (95% CI 21.0-36.4)) were also significantly associated with anal STI, as was younger age (16-34/≥35; RR = 1.7 (95% CI 1.4-2.1); PAF = 15.5 (95% CI 6.4-27.6)) and group sex (RR = 1.3 (95% CI 1.1-1.6); PAF = 9.0 (95% CI -2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.

Background: More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014-2018 in Amsterdam that remained undiagnosed., Methods: We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data., Results: Between 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections in Amsterdan MSM in 2014-2018 remained undiagnosed by 1 May 2019, and 41% [35-48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60-74%] of Amsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 56% [41-70%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37-49%] were in foreign-born MSM, 41% [35-47%] in Dutch-born MSM, 10% [6-18%] in foreign-born heterosexuals, and 5% [2-9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014-2018 originated in transmission chains that pre-existed by 2014., Conclusions: This combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions., Funding: This study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund., Competing Interests: AB, MM, DB, EO, Tv, CF, OR No competing interests declared, Av Funding for managing the ATHENA cohort is supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. Received grants unrelated to this study from European Centre for Disease Prevention and Control paid to author's institution, NP Received grants unrelated to this study from ECDC and Gilead Sciences Hellas, paid to author's institution. Received honoraria for presentations unrelated to this study from Gilead Sciences Hellas, MP Received unrestricted research grants and speaker/ advisory fees from Gilead Sciences, Abbvie and MSD; all of which were paid to author's institute and were unrelated to this study, PR Has received grants unrelated to this study from Gilead Sciences, ViiV Healthcare and Merck, paid to author's institution. Received Honoraria for lecture from Merck paid to institution. Received Honoraria from Gilead Sciences, ViiV Healthcare and Merck, paid to institution, Gd Received honoraria to her Institution for scientific advisory board participations for Gilead Sciences and speaker fees from Gilead Sciences (2019), Takeda (2018-2022) and ExeVir (2020-current), (© 2022, Blenkinsop et al.)

Background: Research suggests shifting patterns of recreational drug consumption among MSM in recent decades. The present study evaluates population-level mean trajectories of substance use among HIV-negative MSM from 1995 to 2019., Methods: Using open cohort study data following MSM in the Netherlands (n=1495) since 1995, we applied generalized estimating equations to examine population-averaged estimates of five substances - alcohol, cannabis, ecstasy, cocaine, and poppers - from 1995 to 2019, as well as their use during sexual encounters., Results: Recent alcohol use decreased; predicted probabilities declined from 1995 to 2019 (.96 to .87). During the same period, cocaine and poppers use increased - (.10 to .23 and .37 to .47, respectively) and use during sex also increased (.05 to .16, and .32 to .41, respectively). Ecstasy use increased over time (.23 to .38), although not during sex. No significant changes in cannabis use occurred., Conclusions: While changes in use of various substances were mixed, increases in cocaine and poppers use during sexual encounters occurred among HIV-negative MSM over time. Efforts to intervene on substance use in connection with sex remain critical for health promotion., Competing Interests: Declarations of Interest Dr. Maria Prins obtained unrestricted research grants and speaker fees from Gilead Sciences, Roche, Abbvie and MSD; all of which were paid to her institute and were unrelated to the current work. All other authors (BCK, LC, SM, & UD) have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To assess frequency and predictors of switching between being on and off PrEP and being lost to follow-up (LTFU) among men who have sex with men (MSM) and transgender women (TGW) with access to PrEP services in Sub-Saharan Africa., Methods: This was a prospective cohort study of MSM and TGW from coastal Kenya who initiated daily oral PrEP from June 2017 to June 2019. Participants were followed monthly for HIV-1 testing, PrEP refill, risk assessment and risk reduction counselling. Follow-up was censored at the last visit before 30 June 2019, or the last HIV-1-negative visit (for those with HIV-1 seroconversion), whichever occurred first. We estimated transition intensities (TI) and predictors of switching: (i) between being off and on PrEP; and (ii) from either PrEP state and being LTFU (i.e. not returning to the clinic for > 90 days) using a multi-state Markov model., Results: In all, 134 participants starting PrEP were followed for a median of 20.3 months [interquartile range (IQR): 7.7-22.1]. A total of 49 (36.6%) people stopped PrEP 73 times [TI = 0.6/person-year (PY), 95% confidence interval (CI): 0.5-0.7] and, of these, 25 (51.0%) restarted PrEP 38 times (TI = 1.2/PY, 95% CI: 0.9-1.7). In multivariable analysis, stopping PrEP was related to anal sex ≤ 3 months, substance-use disorder and travelling. Restarting PrEP was related to non-Christian or non-Muslim religion and travelling. A total of 54 participants were LTFU: on PrEP (n = 47, TI = 0.3/PY, 95% CI: 0.3-0.5) and off PrEP (n = 7, TI = 0.2/PY, 95% CI: 0.1-0.4). In multivariable analysis, becoming LTFU while on PrEP was associated with secondary education or higher, living in the area for ≤ 1 year, residence outside the immediate clinic area and alcohol-use disorder., Conclusions: Switching between being on and off PrEP or becoming LTFU while on PrEP was frequent among individuals at risk of HIV-1 acquisition. Alternative PrEP options (e.g. event-driven PrEP) may need to be considered for MSM and TGW with PrEP-taking challenges, while improved engagement with care is needed for all MSM and TGW regardless of PrEP regimen., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

In the Netherlands, hepatitis C virus (HCV) transmission occurs primarily in men who have sex with men (MSM). By early diagnosis and immediate treatment of acute HCV infections, HCV micro-elimination in MSM is within reach. In cooperation with the community affected, we developed an online HCV-RNA home-based self-sampling test service. This service combined online HCV self-risk assessment with the possibility to test anonymously for HCV-RNA. The service was available in the Netherlands from February 2018 till December 2020 and was promoted online on various dating sites and offline by community volunteers. Using website user data, test results and an online post-test user survey, we evaluated the service and user experiences. The website page with information about testing was visited by 3401 unique users, of whom 2250 used the HCV-risk assessment tool, 152 individuals purchased 194 HCV-RNA tests, and 104 tests were used, of which 101 gave a conclusive result. The target population of MSM at risk was successfully reached with 44.1% of users receiving the advice to test. The test service had a satisfactory uptake (6.8%, 152/2250), a very high HCV-RNA positivity rate (10.9%, 11/101) and was considered acceptable and easy to use by most MSM. We demonstrate that an HCV-RNA home-based self-sampling test service is successful in diagnosing HCV infections among MSM. This service could be a valuable addition to existing sexual healthcare services as it may reach men who are otherwise not tested., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Men who have sex with men (MSM) initiating human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) may increase condomless anal sex (CAS) and number of partners, and, consequently, more often acquire sexually transmitted infections (STIs). Using data from the Amsterdam Cohort Studies, we compared sexual behavior and STI among MSM after PrEP-initiation with controls not initiating PrEP. The MSM reported on sexual behavior and were tested for HIV, chlamydia, gonorrhea, and syphilis semi-annually. We matched MSM who initiated PrEP between January 1, 2015 and December 31, 2019 1:1 to MSM who did not use time-dependent propensity scores based on age, sexual behavior, and STI. Primary end-points were number of casual partners, and proportion with CAS and receptive CAS (rCAS) with casual partners, sexualized drug use (SDU), any STI, and anal STI. We modeled end-points during the 4 years before and 2 years after PrEP-initiation or matched PrEP-initiation timepoint by using logistic regression (dichotomous end-points) or negative binomial regression (count end-point), adjusted for calendar year. Two hundred twenty-eight out of the 858 (26.6%) MSM initiated PrEP. We matched 198 out of 228 (86.8%) to a control. Before PrEP-initiation, end-points increased over time in both groups, with no statistically significant difference. The odds of CAS, rCAS, and anal STI were on average higher after than before PrEP-initiation in PrEP initiators, whereas after versus before differences were not observed in controls. After PrEP-initiation, PrEP initiators had statistically significantly more casual partners, and higher odds of CAS, rCAS, SDU, any STI, and anal STI than controls. These findings support frequent STI screening and counseling in MSM using PrEP.

Background: Global data show that transgender people (TGP) are disproportionally affected by HIV and sexually transmitted infections (STIs); however, data are scarce for Western European countries. We assessed gender identities, sexual behaviour, HIV prevalence and STI positivity rates, and compared these outcomes between TGP who reported sex work and those who did not., Methods: We retrospectively retrieved data from all TGP who were tested at the STI clinics of Amsterdam and The Hague, the Netherlands in 2017-2018. To identify one's gender identity, a 'two-step' methodology was used assessing, first, the assigned gender at birth (assigned male at birth (AMAB)) or assigned female at birth), and second, clients were asked to select one gender identity that currently applies: (1) transgender man/transgender woman, (2) man and woman, (3) neither man nor woman, (4) other and (5) not known yet. HIV prevalence, bacterial STI (chlamydia, gonorrhoea and/or infectious syphilis) positivity rates and sexual behaviour were studied using descriptive statistics., Results: TGP reported all five categories of gender identities. In total 273 transgender people assigned male at birth (TGP-AMAB) (83.0%) and 56 transgender people assigned female at birth (TGP-AFAB) (17.0%) attended the STI clinics. Of TGP-AMAB, 14,6% (39/267, 95% CI 10.6% to 19.4%) were HIV-positive, including two new diagnoses and bacterial STI positivity was 15.0% (40/267, 95% CI 10.9% to 19.8%). Among TGP-AFAB, bacterial STI positivity was 5.6% (3/54, 95% CI 1.2% to 15.4%) and none were HIV-positive. Sex work in the past 6 months was reported by 53.3% (137/257, 95% CI 47.0% to 59.5%) of TGP-AMAB and 6.1% (3/49, 95% CI 1.3% to 16.9%) of TGP-AFAB. HIV prevalence did not differ between sex workers and non-sex workers., Conclusion: Of all TGP, the majority were TGP-AMAB of whom more than half engaged in sex work. HIV prevalence and STI positivity rates were substantial among TGP-AMAB and much lower among TGP-AFAB. Studies should be performed to provide insight into whether the larger population of TGP-AMAB and TGP-AFAB are at risk of HIV and STI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The uptake of preexposure prophylaxis (PrEP) against HIV is low among young men who have sex with men (MSM) in the Netherlands. Studying the intention to use PrEP among non-PrEP using young and older MSM can guide health authorities in developing new prevention campaigns to optimize PrEP uptake., Methods: We investigated the sociodemographic, behavioral, and psychosocial factors associated with a high PrEP use intention in the coming 6 months among 93 young MSM (aged ≤25 years), participating in an online survey, and 290 older MSM (aged ≥26 years), participating in an open, prospective cohort in 2019 to 2020., Results: Perceiving PrEP as an important prevention tool was associated with a high PrEP use intention among young and older MSM. Among young MSM, a high level of PrEP knowledge and believing that PrEP users take good care of themselves and others were associated with a high PrEP use intention. Among older MSM, 2 or more anal sex partners, chemsex, high HIV risk perception, and believing PrEP increases sexual pleasure were associated with a high PrEP use intention. Believing PrEP leads to adverse effects was associated with a low intention to use PrEP among older MSM., Conclusions: To conclude, we showed that both behavioral and psychosocial factors were associated with a high PrEP use intention among young and older MSM. In addition to focusing on sexual behavior and HIV risk, future prevention campaigns and counseling on PrEP could incorporate education, endorsing positive beliefs, and disarming negative beliefs to improve the uptake of PrEP in young and older MSM., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.

Objectives: To assess differences in socio-demographics, HIV testing and healthcare seeking behavior between individuals diagnosed late and those diagnosed early after HIV-acquisition., Design: Cross-sectional study among recently HIV-diagnosed migrant and non-migrant individuals living in the Netherlands., Methods: Participants self-completed a questionnaire on socio-demographics, HIV-testing and healthcare seeking behavior preceding HIV diagnosis between 2013-2015. Using multivariable logistic regression, socio-demographic determinants of late diagnosis were explored. Variables on HIV-infection, testing and access to care preceding HIV diagnosis were compared between those diagnosed early and those diagnosed late using descriptive statistics., Results: We included 143 individuals with early and 101 with late diagnosis, of whom respectively 59/143 (41%) and 54/101 (53%) were migrants. Late diagnosis was significantly associated with older age and being heterosexual. Before HIV diagnosis, 89% of those with early and 62% of those with late diagnosis had ever been tested for HIV-infection (p<0.001), and respectively 99% and 97% reported healthcare usage in the Netherlands in the two years preceding HIV diagnosis (p = 0.79). Individuals diagnosed late most frequently visited a general practitioner (72%) or dentist (62%), and 20% had been hospitalized preceding diagnosis. In these settings, only in respectively 20%, 2%, and 6% HIV-testing was discussed., Conclusion: A large proportion of people diagnosed late had previously tested for HIV and had high levels of healthcare usage. For earlier-case finding of HIV it therefore seems feasible to successfully roll out interventions within the existing healthcare system. Simultaneously, efforts should be made to encourage future repeated or routine HIV testing among individuals whenever they undergo an HIV test., Competing Interests: The authors have declared that no competing interests exist.

Aims: To test whether recreational drug use (RDU) and sexualized drug use (SDU) changed in the Amsterdam area between 2008 and 2018 and quantify associations of SDU with condomless anal sex (CAS), recent human immunodeficiency virus (HIV) or sexually transmitted infections (STI) among human immunodeficiency virus (HIV)-negative men who have sex with men (MSM)., Design: Open prospective cohort study., Setting: Public Health Service of Amsterdam, the Netherlands., Participants: A total of 976 HIV-negative MSM, aged ≥ 18 years., Measurements: Self-reported RDU and sexual behaviour in the past 6 months. Laboratory-confirmed HIV and STI (chlamydia, gonorrhoea and syphilis). We studied: any RDU; any SDU (i.e. any RDU during sex); specific SDU (i.e. use of mephedrone, methamphetamine, gamma-hydroxybutyric acid/gamma-butyrolactone, ketamine, amphetamine, cocaine and/or ecstasy during sex); use of individual drugs; and use of individual drugs during sex. We evaluated changes over calendar years in the proportion of individuals with these end-points [using logistic regression with generalized estimating equations (GEE)] and number of drugs (using negative binomial regression with GEE), adjusted for current age, country of birth and education level., Findings: Median age of participants in 2008 was 33.2 years (interquartile range = 27.8-40.1); 83.1% were born in the Netherlands. The proportion of any RDU increased from 67.2% in 2008 to 69.5% in 2018 [adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.03-1.51]. Any SDU increased from 53.8% in 2008 to 59.8% in 2013 (aOR = 1.23; 95% CI = 1.07-1.42) and remained stable afterwards. Specific SDU increased from 25.0% in 2008 to 36.1% in 2018 (aOR = 2.10; 95% CI = 1.71-2.58). The average number of drugs used increased for those reporting any RDU, any SDU and specific SDU (all P < 0.05. Among those engaging in sex, any SDU was associated with CAS (aOR = 1.36; 95% CI = 1.19-1.55), HIV (aOR = 5.86; 95% CI = 2.39-14.4) and STI (aOR = 2.31; 95% CI = 1.95-2.73). Specific SDU was associated with CAS (aOR = 1.58; 95% CI = 1.37-1.81), HIV (aOR = 6.30; 95% CI = 3.28-12.1) and STI (aOR = 2.15; 95% CI = 1.81-2.55)., Conclusions: Among human immunodeficiency virus (HIV)-negative men who have sex with men in Amsterdam, recreational drug use, including sexualized drug use, increased between 2008 and 2018. Sexualized drug use was strongly associated with condomless anal sex, HIV and sexually transmitted infections., (© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Aims: Major declines in HIV and hepatitis C and B virus (HCV/HBV) incidence among people who inject drugs (PWID) have been attributed to early implementation of harm-reduction programs (HRP) in the Netherlands, but alternative factors such as selective mortality and demographic and drug market shifts over time probably contributed to observed incidence declines. We quantified and tested the effect of HRP participation on risk of these infections among PWID in Amsterdam, the Netherlands., Design: We emulated the design of a hypothetical, ideal randomized trial using observational data from the Amsterdam Cohort Studies (1985-2014)., Setting: Amsterdam, the Netherlands., Participants: We included PWID who ever used opioids, had a recent history of injecting drug use (IDU) and tested negative for HIV, HCV or HBV. Of 983 participants, 640, 137 and 308 were included for the HIV, HCV and HBV analyses and 59, 45 and 49 seroconversions were observed, respectively., Interventions: Intervention arms were: complete HRP participation [≥ 60 mg/day methadone and 100% needle and syringe program (NSP) coverage, or any methadone dose if no recent injection drug use] versus no HRP and partial HRP participation combined (< 60 methadone mg/day and/or < 100% NSP coverage)., Conclusions: Complete participation in harm reduction programs appears to have led to substantial decreases in HIV and hepatitis C and B virus acquisition risk among people who inject drugs in the Netherlands., Measurements: Separately for each infection, we estimated the hazard ratios (HR) comparing HRP arms using marginal structural models., Findings: Compared with no/partial HRP participation, complete HRP participation led to lower risk of HIV [HR = 0.54, 95% confidence interval (CI) = 0.27-1.08], HCV (HR = 0.16, 95% CI = 0.06-0.40) and HBV (HR = 0.28, 95% CI = 0.13-0.61) acquisition., (© 2021 Society for the Study of Addiction.)

Background: Migrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents., Methods: In this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory., Results: Of the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (p<0.001). Prevalence of chronic HCV infection (HCV-RNA-positive) was 0.7% (n = 3/435, 95%CI 0.1% to 2.0%, all new infections) and HIV infection 1.1% (n = 5/439, 95%CI 0.04% to 2.6%, 40% new infection)., Conclusion: Prevalence of chronic HBV, chronic HCV and HIV infections in our study population is higher compared to the Dutch population, thus emphasizing the importance of case finding for these infections through primary care and public health in this specific group of migrants. Screening uptake could be improved by on-site testing., Competing Interests: The authors have declared that no competing interests exist.

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Improving adherence to preexposure prophylaxis (PrEP) by providing automated feedback on self-reported PrEP use via a mobile application (app)., Design: Randomized clinical trial among MSM participating in the Amsterdam PrEP demonstration project (AMPrEP)., Methods: Eligible participants were randomized 1 : 1 to the control or intervention app. Both allowed daily reporting of sexual behaviour and medication intake; the intervention app also provided visual feedback. Dried blood spots collected at 12 and 24 months yielded intracellular tenofovir diphosphate concentrations (TFV-DP). We assessed proportions of participants with poor (TFV-DP <700 fmol/punch; primary outcome), good (TFV-DP ≥700 fmol/punch) and excellent (TFV-DP ≥1250 fmol/punch; secondary outcome) adherence at both time-points, and the association with the control or intervention app., Results: We randomized 229 participants, 118 to the intervention and 111 to the control arm. The primary, per-protocol, analysis included 83 participants per arm. In total, 22/166 (13%) of participants adhered poorly, 144/166 (87%) good and 66/166 (40%) excellently. App feedback did not result in a lower proportion of participants with poor adherence [control: 9 of 83 (11%); intervention: 13 of 83 (16%); P = 0.36]. App feedback did result in a larger proportion of participants with excellent adherence [control: 26/83 (31%); intervention: 40/83 (48%); P = 0.026]., Conclusion: In this highly adherent population, app feedback did not improve the proportion of participants with poor adherence to PrEP.Clinical Trial Number Netherlands Trial Register: NL5413., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed., Methods: Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection., Results: In total, 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range [IQR] 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (IQR 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3., Conclusions: Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: As biomedical advances improved HIV treatment, the perceptions of severity and anticipated consequences of HIV could have changed accordingly. This study investigates the current perceptions of severity and anticipated consequences of HIV infection and its association with sexual risk behaviour among HIV-negative and never-tested men who have sex with men (MSM) living in the Netherlands., Methods: In-depth interviews with recently diagnosed HIV-positive MSM were used to develop a questionnaire measuring the perceived severity and anticipated consequences of HIV infection. The questionnaire was distributed online between April and July 2019. A structural equation model was constructed to explore the anticipated consequences contributing to the perceived HIV severity and to assess the association between the perceived severity and sexual risk behaviour., Results: In total, 1,072 HIV-negative and never-tested MSM completed the questionnaire, of whom 28% reported recent sexual risk behaviour. Almost one-quarter of participants (23%) had a low perceived HIV severity, which was associated with more prevalent sexual risk taking (β = -0.07, 95% CI = -0.12/-0.01). In this model, the perceived severity of HIV was more strongly associated with anticipated psychological consequences of HIV (β = 0.34, 95% CI = 0.24 to 0.44) and to a lesser extent with anticipated negative consequences of HIV on sex/relationships (β = 0.28, 95% CI = 0.19 to 0.38) and disclosure-related consequences (β = 0.16, 95% CI = 0.07 to 0.26). Health-related consequences of HIV were not significantly associated with the severity perceptions (β = 0.06, 95% CI = -0.03 to 0.14)., Conclusions: Anticipated negative social and psychological consequences of HIV mostly contribute to high HIV-severity perceptions in MSM. A smaller subgroup of MSM does not perceive HIV as a serious disease, which is associated with increased sexual risk taking. Efforts to normalize living with HIV are essential but might present a challenge for HIV prevention as it could, for a minority of MSM, decrease the motivation to prevent HIV infection., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Objectives: To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands., Methods: We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than €20 000 per QALY gained was considered cost-effective., Results: Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP., Conclusions: A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Daily and event-driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event-driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence., Methods: We analysed pooled data from two prospective cohort studies among MSM: Be-PrEP-ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three-monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018., Results and Discussion: We included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94)., Conclusions: A quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Pre-Exposure Prophylaxis (PrEP) is a novel HIV prevention tool. PrEP stigma is a frequently reported barrier, while social disclosure of PrEP use may be an important facilitator. We explored how PrEP users managed PrEP use disclosure using a symbolic interactionist approach. We interviewed 32 participants from two PrEP demonstration projects (Be-PrEP-ared, Antwerp; AMPrEP, Amsterdam). We validated qualitative findings through Be-PrEP-ared questionnaire data. A minority of participants had received negative reactions on PrEP. The way PrEP use was disclosed was highly dependent on the social situation. In a sexual context among MSM, PrEP use was associated with condomless sex. Friends endorsed PrEP use as a healthy choice, but also related it to carelessness and promiscuity. It was seldom disclosed to colleagues and family, which is mostly related to social norms dictating when it is acceptable to talk about sex. The study findings reveal that PrEP stigma experiences were not frequent in this population, and that PrEP users actively manage disclosure of their PrEP user status. Frequent disclosure and increased use may have helped PrEP becoming normalised in these MSM communities. To increase uptake, peer communication, community activism and framing PrEP as health promotion rather than a risk-reduction intervention may be crucial., (© 2021 Foundation for the Sociology of Health & Illness.)

Background: It is unclear whether unrestricted access and high uptake of direct-acting antivirals (DAAs) is sufficient to eliminate hepatitis C virus (HCV) in high-risk populations such as men who have sex with men (MSM). This study presents historic trends and current dynamics of HCV transmission among MSM in Amsterdam based on sequence data collected between 1994 and 2019., Methods: Hypervariable region 1 sequences of 232 primary HCV infections and 56 reinfections were obtained from 244 MSM in care in Amsterdam. Maximum-likelihood phylogenies were constructed for HCV genotypes separately, and time-scaled phylogenies were constructed using a Bayesian coalescent approach. Transmission clusters were determined by Phydelity and trends in the proportion of unclustered sequences over time were evaluated using logistic regression., Results: Seventy-six percent (218/288) of sequences were part of 21 transmission clusters and 13 transmission pairs. Transmission cluster sizes ranged from 3 to 44 sequences. Most clusters were introduced between the late 1990s and early 2010s and no new clusters were introduced after 2012. The proportion of unclustered sequences of subtype 1a, the most prevalent subtype in this population, fluctuated between 0% and 20% in 2009-2012, after which an increase occurred from 0% in 2012 to 50% in 2018., Conclusions: The proportion of external introductions of HCV infections among MSM in Amsterdam has recently increased, coinciding with high DAA uptake. Frequent international transmission events will likely complicate local microelimination efforts. Therefore, international collaboration combined with international scale-up of prevention, testing, and treatment of HCV infections (including reinfections) is warranted, in particular for local microelimination efforts., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Men who have sex with men (MSM) with acute human immunodeficiency virus (HIV) infection (AHI) are a key source of new infections. To curb transmission, we implemented a strategy for rapid AHI diagnosis and immediate initiation of combination antiretroviral therapy (cART) in Amsterdam MSM. We assessed its effectiveness in diagnosing AHI and decreasing the time to viral suppression., Methods: We included 63 278 HIV testing visits in 2008-2017, during which 1013 MSM were diagnosed. Standard of care (SOC) included HIV diagnosis confirmation in < 1 week and cART initiation in < 1 month. The AHI strategy comprised same-visit diagnosis confirmation and immediate cART. Time from diagnosis to viral suppression was assessed for 3 cART initiation periods: (1) 2008-2011: cART initiation if CD4 < 500 cells/μL (SOC); (2) January 2012-July 2015: cART initiation if CD4 < 500 cells/μL, or if AHI or early HIV infection (SOC); and (3a) August 2015-June 2017: universal cART initiation (SOC) or (3b) August 2015-June 2017 (the AHI strategy)., Results: Before implementation of the AHI strategy, the proportion of AHI among HIV diagnoses was 0.6% (5/876); after implementation this was 11.0% (15/137). Median time (in days) to viral suppression during periods 1, 2, 3a, and 3b was 584 (interquartile range [IQR], 267-1065), 230 (IQR, 132-480), 95 (IQR, 63-136), and 55 (IQR, 31-72), respectively (P < .001)., Conclusions: Implementing the AHI strategy was successful in diagnosing AHI and significantly decreasing the time between HIV diagnosis and viral suppression., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: An accurate point-of-care test for tuberculosis (TB) in children remains an elusive goal. Recent evaluation of a novel point-of-care urinary lipoarabinomannan test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan (FujiLAM), in adults living with human immunodeficiency virus (HIV) showed significantly superior sensitivity than the current Alere Determine Tuberculosis Lipoarabinomannan test (AlereLAM). We therefore compared the accuracy of FujiLAM and AlereLAM in children with suspected TB., Methods: Children hospitalized with suspected TB in Cape Town, South Africa, were enrolled (consecutive admissions plus enrichment for a group of children living with HIV and with TB), their urine was collected and biobanked, and their sputum was tested with mycobacterial culture and Xpert MTB/RIF or Xpert MTB/RIF Ultra. Biobanked urine was subsequently batch tested with FujiLAM and AlereLAM. Children were categorized as having microbiologically confirmed TB, unconfirmed TB (clinically diagnosed), or unlikely TB., Results: A total of 204 children were enrolled and had valid results from both index tests, as well as sputum microbiological testing. Compared to a microbiological reference standard, the sensitivity of FujiLAM and AlereLAM was similar (42% and 50%, respectively), but lower than that of Xpert MTB/RIF of sputum (74%). The sensitivity of FujiLAM was higher in children living with HIV (60%) and malnourished children (62%). The specificity of FujiLAM was substantially higher than that of AlereLAM (92% vs 66%, respectively). The specificity of both tests was higher in children 2 years or older (FujiLAM, 96%; AlereLAM, 72%)., Conclusions: The high specificity of FujiLAM suggests utility as a "rule-in" test for children with a high pretest probability of TB, including hospitalized children living with HIV or with malnutrition., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Pre-exposure prophylaxis (PrEP) is a promising strategy to reduce HIV incidence among men who have sex with men (MSM). How and when PrEP is used could in part be influenced by its impact on the sexual well-being of its users. Yet, the impact of PrEP on sexual well-being has received little attention in current literature and is not well-understood. We conducted 43 in-depth interviews (June 2017-June 2018) with HIV-negative MSM who started PrEP within the Amsterdam PrEP study. We used purposive sampling to select participants who (1) reported changes on well-being indicators; (2) switched between PrEP-dosing regimens; (3) neither changed regimens nor changed on well-being indicators. Transcribed interviews were qualitatively analyzed by means of an open-coding process. Results showed that PrEP minimized HIV-related fear, increased self-esteem, and reduced stigma and shame about having condomless anal sex. The psychological relief provided by PrEP also enabled relaxation which reduced pain during anal sex. PrEP use increased the diversity of partner choices and improved the perceived quality of sexual relationships and the ability to develop relationships. Along with this positive impact, almost half of interviewees reported concurrent negative experiences. In some cases, PrEP triggered more extreme sexual behaviors and/or problematic increases in preoccupation with sex and drug use. These were perceived as having a negative impact on sexual relationships, sexual well-being, PrEP adherence, and general health. In conclusion, our findings suggest that PrEP contributes to improvements in sexual well-being that go beyond protection from HIV. Counseling strategies should be devised to help PrEP users mitigate possible co-existing negative consequences of PrEP use.

Introduction: Event-driven pre-exposure prophylaxis (edPrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for preventing HIV acquisition in men who have sex with men (MSM) and is preferred over daily PrEP by some MSM. However, it is largely unknown how well MSM adhere to edPrEP. We then aimed to assess PrEP protection during CAS among MSM using edPrEP and participating in the Amsterdam PrEP demonstration project (AMPrEP)., Methods: We analysed data from participants enrolled in AMPrEP who were taking edPrEP. We measured adherence through (1) a mobile application in which sexual behaviour and PrEP-use were recorded daily, (2) three-monthly self-completed questionnaires and (3) dried blood spot (DBS) samples collected around six, twelve and twenty-four months after PrEP initiation. We assessed the proportion of days with condomless anal sex (CAS) acts that were protected by PrEP, per partner type (i.e. steady partners, known casual partners, unknown casual partners), and the proportion of three-month periods during which PrEP was correctly used. Intracellular TFV-diphosphate (TFV-DP) concentrations were determined from DBS. Good adherence was defined as at least one tablet before and one tablet within 48 hours after a CAS act., Results: Between 11 September 2015 and 6 October 2019, 182 of 376 MSM (48.4%) used edPrEP for at least one three-month period. Of the 8224 CAS days that were reported in the app during edPrEP-use, we observed good protection for most CAS days involving steady partners (n = 1625/2455, 66.9%), known casual partners (n = 3216/3472, 92.6%) and unknown casual partners (n = 2074/2297, 90.3%). Men reported consistently correct PrEP-use in 851 (81.4%) of the 1046 three-month periods of edPrEP-use. The median TFV-DP concentration was 591 fmol/sample (interquartile range = 270 to 896)., Conclusions: Adherence to edPrEP was high as determined from the online app and questionnaire. DBS measurements were consistent with two to three tablets per week on average., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015., Methods: In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years., Findings: Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5·2 per 1000 person-years [95% CI 5·0-5·5]). The highest incidence was observed in men who have sex with men (MSM; 7·7 per 1000 person-years [7·3-8·2]) and was lower in people who inject drugs (PWID; 1·7 per 1000 person-years [0·7-4·1]) and other key populations (1·0 per 1000 person-years [0·8-1·2]). In MSM, incidence increased in 2007 to 14·3 per 1000 person-years and fluctuated between 8·7 and 13·0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6·1 cases per 1000 person-years and remained steady between 4·1 and 4·9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26·9 per 1000 person-years [95% CI 23·9-30·3]). The highest incidence rate was observed in MSM (38·5 per 1000 person-years [33·9-43·7]) and was lower in PWID (10·9 per 1000 person-years [3·5-33·8]) and other key populations (8·9 per 1000 person-years [6·3-12·5]). In MSM, reinfection incidence fluctuated between 38·0 and 88·9 per 1000 person-years from 2006 to 2015, reaching 55·6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41·4 per 1000 person-years, followed by further decreases to 24·4 per 1000 person-years in 2017 and 11·4 per 1000 person-years in 2019., Interpretation: The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures., Funding: Dutch Ministry of Health, Welfare, and Sport., (Copyright © 2021 Elsevier Ltd. All rights reserved.)