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Introduction: Scarcely available European studies suggest that migrant female sex workers (FSW) have a higher likelihood of sexually transmitted infections (STI) but a lower likelihood of HIV compared to non-migrant FSW. This study assessed demographics, STI/HIV burden, and engagement in sexual healthcare among first-generation (FGM) and second-generation (SGM) migrant FSW versus Western-born FSW., Methods: This large retrospective cohort study included 27,532 Dutch STI clinic consultations from 11,363 individual FSW between 2016 and 2021. STI diagnoses (chlamydia/gonorrhoea/ infectious syphilis/infectious hepatitis B/HIV) in the first consultation were compared using Chi-squared test. Logistic regression adjusting for age, urbanity and sexual behaviour assessed associations between migration status and STI diagnoses. Incidence of repeat consultation was compared between migration groups using Cox proportional hazards regression, adjusting for age and STI clinic urbanity., Results: FGM FSW ( n = 5085) mostly originated from Eastern Europe (50.5 %) and SGM FSW ( n = 1309) from Suriname/Netherlands Antilles (36.3 %). Among FGM, SGM and Western-born FSW, 11.4 %, 15.2 % and 13.3 %, respectively ( p < 0.001) were diagnosed with any STI. FGM FSW had a lower odds (aOR 0.78, 95 %:CI 0.65-0.94, p < 0.01) of chlamydia or gonorrhoea diagnosis, but a higher aOR (6.38,95 %CI:2.63-15.49, p < 0.001) of HIV, syphilis, or hepatitis B diagnosis in the first consultation. FGM FSW had a lower likelihood of a repeat consultation at any time (aHR:0.73,95 %CI:0.69-0.77, p < 0.001) than Western-born FSW., Conclusion: Migrant FSW versus Western-born FSW demonstrated a varying burden of STI, FGM heightened proportions and odds of infectious syphilis, hepatitis B and HIV and lower likelihood of repeat consultations. Enhancing accessibility and outreach efforts for migrant FSW in sexual healthcare services is imperative., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Pre-exposure prophylaxis (PrEP) use prevents HIV transmission, and may lead to changes in sexual behavior. We aimed to explore sexual behavior over time, and identify predictors of behavior change in men who have sex with men (MSM) using PrEP at sexual health centers (SHC) in the Netherlands. We used longitudinal data from the national STI surveillance database (January 2018-June 2021) of HIV-negative MSM who first initiated PrEP in the national PrEP pilot. We modelled behavior change after PrEP initiation, and identified predictors of behavior change using multi-state Markov models. The probability of stopping group sex, chemsex, use of poppers or erection stimulants, and having ≥ 10 partners in the past 6 months among included MSM (n = 4,349, n SHC visits = 21,820) was higher compared to the probability of starting with these behaviors after PrEP initiation. However, MSM who used condoms consistently during anal sex had a high probability of changing to inconsistent condom use (0.8) at the next visit, and inconsistent condom users mostly remained inconsistent (0.8). First visit, visiting the SHC more often (vs. regular), and STI diagnosis were predictors of starting or continuing with most of the behaviors associated with increased risk. Behavior change was less likely among older participants (> 34 compared to ≤ 34 years), and during COVID-19 lockdown and post-lockdown periods compared to pre-COVID-19. Although condom use decreased over time, transitions towards stopping with other behaviors associated with increased likelihood of acquiring an STI after PrEP initiation were common. This may suggest increased sexual empowerment, especially among younger MSM. Predictors of behavior change may help to identify MSM who are likely to start with or continue to engage in these behaviors in the near future and to provide suitable and timely counselling about behavior and PrEP adherence., (© 2024. The Author(s).)

The hepatitis C virus (HCV) prevalence is high among men who have sex with men (MSM) with HIV in the Netherlands. Large reductions in HCV incidence among MSM with HIV, however, have occurred since treatment with direct-acting antivirals. Over the years, a broader understanding of the HCV epidemic has shown that HCV infections are not solely restricted to MSM with HIV, but they also occur among HIV-negative MSM. Currently, HCV testing among HIV-negative MSM is only provided for PrEP users and is not part of routine sexually transmitted infection (STI) screening among HIV-negative MSM who are not using PrEP. In this study, we screened 1885 HIV-negative MSM who did not participate in a PrEP program, with over 1966 STI screening visits at four different public health clinic sites. Among the 1885 MSM, only one person had a new HCV infection, resulting in a 0.05% (95% confidence interval 0.0-0.3) incidence. Based on our findings, we can conclude that systematic HCV testing at STI clinics may not yield significant benefits for this particular population.

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.)

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.)

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.)

Upon agonist binding the heteromeric glucocorticoid receptor complex undergoes a conformational change (receptor activation). This event involves the dissociation of a dimer of 90 kDa heat shock proteins. Whereas receptor activation in cytosolic assays is both rapid and irreversible, less is known about the receptor activation and translocation in intact cells during challenge with an agonist. In this paper we report on the receptor status of glucocorticoid-sensitive murine S49 lymphoma cells during dexamethasone exposure. By three different assays, ligand (re)binding, nuclear translocation and hsp90 co-immunoprecipitation, it was found that the majority of the glucocorticoid receptor protein was in a non-activated conformation. Furthermore, prolonged exposure to dexamethasone did not result in increased levels of activated receptors. By assessing receptor activation in situ we found that physiological temperature was less effective in dissociating hsp90 compared to room temperature. These findings indicate that the physiological temperature negatively controls receptor activation, probably due to a thermolabile interaction between the hormone and its cognate receptor.

The validity of in vitro assays in predicting the susceptibility of leukaemic cells to glucocorticoid-mediated lysis was evaluated in a panel of six murine leukaemia cell lines. In this panel susceptibility to glucocorticoids ranged from highly sensitive to fully resistant. The panel was screened for specific 3H-dexamethasone binding in whole cells and for activation of cytosolic receptors in cell lysates. Specific binding of 3H-dexamethasone was strongly affected by the incubation temperature. In all cell lines, rapid and reversible changes were observed in the stability of agonist-receptor association with a transition temperature of 28 degrees C. Below this temperature, intracellular receptors were found to be in a stable-binding, high-affinity configuration, masking differences in receptor status among the various cell lines. When assayed at 37 degrees C, refractory and fully resistant cells revealed nonsaturating, low-affinity binding of steroid. Saturating, high-affinity binding was, however, restored in these cells by the drug meta-iodobenzylguanidine with concomitant sensitization to dexamethasone-induced lysis. Contrary to observations with intact cells, heat-induced agonist-receptor dissociation in cytosols caused irreversible loss of (re)binding capacity. Activation of cytosolic receptors only recognized fully resistant cell lines as being deficient in the transformation of liganded receptors into a DNA-binding configuration. The assay, however, could not discriminate between three cell lines with highest but varying degrees of sensitivity because of maximal activation. The results indicate that non-physiological temperature and cell disruption strongly and differentially affect steroid binding and receptor activation, respectively. The observations may account for the poor correlation between conventional predictive assays and steroid responsiveness in clinical leukaemia.