When awareness is not a barrier to PrEP uptake among men who have sex with men who are eligible for PrEP in France.

Despite PrEP being available and free of charge in France, a gap remains between the estimated number of men who have sex with men (MSM) with high-risk exposure to HIV and the number of MSM PrEP users. The objective of this study is to identify factors associated with non-intention to use PrEP among PrEP-eligible and PrEP-aware MSM in France, "non-intenders".European MSM Internet Survey (EMIS)-2017 was a cross-sectional survey conducted among MSM concerning their HIV prevention needs. Logistic regression models were used to identify factors associated with "non-intenders".Compared to PrEP users, factors associated with non-intention to use PrEP were: age (aOR[95%CI] = 3.80[2.21;6.53]); not being vaccinated against hepatitis B (2.20[1.45;3.34]); self-efficacy (1.84[1.29;2.60]); lower knowledge about on-demand PrEP (11.48[7.37;17.87]) and daily PrEP (2.58[1.27;5.25]); not having a PrEP discussion at a hospital (12.39[8.90;17.27]) or at a community service/drop-in (4.93[3.48;6.97]); living in a department with few PrEP access points (1.70[1.10;2.63]).On-demand PrEP may meet the prevention needs of "non-intenders" who have lower HIV risk perception. Increasing communication from health providers and community health workers to all MSM is needed.

Gradient of vaccine hesitancy among French men having sex with men: An electronic cross-sectional survey in 2022.

In developed countries, vaccinations against hepatitis B (HBV), hepatitis A (HAV), and human papillomavirus (HPV) are often recommended to men who have sex with men (MSM) because of the risky sexual practices in which some engage. Vaccine coverage against these diseases is not optimal in France, probably due in part to vaccine hesitancy (VH). The overall aim of this survey among MSM was to estimate the prevalence of different grades of VH for these vaccines as well as of general VH (toward any vaccine). The specific objectives were to study the sociodemographic correlates of MSM specific and general VH and its association with vaccine uptake. A cross-sectional electronic survey (February-August 2022) collected information from 3,730 French MSM about their perceptions of HBV, HAV, and HPV and their related vaccines, to construct "specific VH" variables. Information about their past vaccination behaviors for any vaccine was used to construct a "general VH" variable, based on the World Health Organization definition. Almost 90% of MSM showed moderate or high specific VH for HBV, HAV, and/or HPV, and 54% general VH. A higher education level and comfortable financial situation were associated with lower grades of specific and general VH. Younger age was associated with less frequent specific VH and more frequent general VH. Specific VH, versus general, was more strongly associated with frequent self-reported non-vaccination against these three disease. Addressing their concerns about vaccines, improving their knowledge of vaccine-preventable sexually transmitted infections, and motivating them to get vaccinated are public health priorities.

[Use of heparin calibrated anti-Xa assay for apixaban and rivaroxaban measurement in the context of regional telestroke activity]. / Estimation de la concentration en apixaban et en rivaroxaban par l'activité anti-Xa héparine en contexte d'activité régionale de télé-AVC.

INTRODUCTION: In Bordeaux University Hospital, neurologists are required to prescribe thrombolysis using telemedicine (telethrombolysis) for anticoagulated stroke patients admitted in peripheral centers in the Nouvelle-Aquitaine region. However, due to the bleeding risk, the maximum concentration of DOAC authorizing thrombolysis is 30, 50 or 100 ng/mL (depending on the sources and the patient-specific benefit-risk ratio). Most of the time, specific assays of Direct Oral Anticoagulants (DOACs) are not available in these peripheral centers. We therefore studied an alternative test: the Unfractionated Heparin (UFH) anti-Xa activity which is available in most laboratories and could be used to estimate the DOAC concentration. METHODS: Five centers were included in our study: three centers using the Liquid Anti-Xa HemosIL® Werfen reagent and two centers using the STA-Liquid Anti-Xa® Stago reagent. For each reagent, we established correlation curves between DOAC and UFH anti-Xa activities and determinated UFH cut-offs for the thresholds of 30, 50 and 100 ng/mL respectively. RESULTS: A total of 1455 plasmas were tested. There is an excellent correlation between DOAC and UFH anti-Xa activities using a third-degree modeling curve, independently the reagent used. However, a significant inter-reagent variability is observed concerning the obtained cut-offs. CONCLUSION: Our study makes unsuitable the use of a universal cut-off. In opposition to recommendations made by other publications, the UFH cut-offs must be adapted to the reagent used locally by the laboratory, and to the considered DOAC.

Comparing failure tests on pharmaceutical tablets: Interpretation using experimental results and a numerical approach with cohesive zone models.

The mechanical strength is an important quality attribute of pharmaceutical tablets. It can be determined using different failure tests like the Brazilian test or the three-point bending test. Nevertheless, literature shows that different failure tests often give conflicting values of tensile strengths (TS), which are generally calculated using the maximum stress criterion as a failure criterion. This work started from the hypothesis that these discrepancies are in fact due to the application of this criterion which is not suited to study pharmaceutical tablets, first due to heterogeneity of the stress distributions during the tests and second due to the quasi-brittle nature of pharmaceutical tablets. As an alternative, a numerical fracture criterion which is known to be well-suited for quasi-brittle solids (cohesive zone model, CZM) was used and calibrated using experiments. Using this approach, the breaking forces obtained numerically were shown to be in fair agreement with the experimental ones. Above all, the numerical results made it possible to catch the trends when comparing the different failure tests one to another. Especially, the model made it possible to retrieve the factor 2 between the TS obtained by three-point bending and by diametral compression found in the literature.

Impact of the early 2020 COVID-19 crisis and lockdown on PrEP use among men who have sex with men (MSM) in France.

OBJECTIVE: To describe changes in pre-exposure prophylaxis (PrEP) use during and following the COVID-19 lockdown in France (March-May 2020) and identify the factors associated with PrEP discontinuation among men who have sex with men (MSM) after the lockdown. METHODS: Data from the, an anonymous, cross-sectional internet survey among MSM in July 2020, were analysed. Among respondents who were using PrEP prior to the lockdown, a binary logistic regression model was used to compare participants who were still taking PrEP (current PrEP users) with those who were not taking PrEP at the time of the survey (former PrEP users). RESULTS: Among 8345 respondents, 946 were PrEP users before the lockdown, of whom 58.8% (n=556) reported stopping PrEP during the lockdown and 15.4% (n=146) were not using PrEP at the time of the survey. Among the 556 who stopped PrEP during lockdown, 86.5% (n=481) reported no sexual activity; 76.8% (n=427) restarted PrEP after lockdown. Former PrEP users were more likely to be younger, not living with a stable male sexual partner, report moderate anxiety, report increased psychoactive drug use during the lockdown, and report not having tested for HIV or STI since the end of the lockdown because they did not know where to go, preferred to wait or for another reason. Reporting fewer male sexual partners in the last 6 months was also significantly associated with being a former PrEP user. CONCLUSIONS: MSM adapted PrEP use to their sexual activity during and after the French lockdown. After the lockdown, discontinued PrEP occurred more often among MSM who had fewer sexual partners and had mental health vulnerabilities. These factors could also be predictive of PrEP discontinuation in a more general context. PrEP users should be informed on how to safely stop/start PrEP and on the use of other prevention tools to reduce potential risk exposure during PrEP discontinuation.

Are PrEP services in France reaching all those exposed to HIV who want to take PrEP? MSM respondents who are eligible but not using PrEP (EMIS 2017).

Pre-exposure prophylaxis (PrEP) is fully reimbursed by the French health insurance system since 2016. However, uptake of PrEP is slower than expected and little is known about men who have sex with men (MSM) who are eligible for PrEP according to French guidelines, but not using it. This study aims to (1) assess and describe MSM that are eligible to PrEP but not using it, and (2) identify potential individual and structural barriers of PrEP uptake among eligible MSM who are aware and intend to take PrEP. Data from EMIS-2017, a cross-sectional internet survey among gay, bisexual, and other MSM, were used. Among 7965 respondents without diagnosed HIV, 9.2% were PrEP users. Among 7231 non-PrEP users, 35.2% were eligible to PrEP and 15.2% were eligible, aware and intended to take PrEP. Eligible MSM who are not using PrEP are mostly younger, students, less "out", living in small cities, using condoms more frequently but still with low self-efficacy regarding safe sex and more distant from preventive health care and information than PrEP users. Despite free PrEP availability in France, results suggest that PrEP is not fully accessible and that there is a need to increase PrEP demand and decentralize PrEP delivery.

Becoming adherent to a preventive treatment for HIV: a qualitative approach.

The clinical trial ANRS-IPERGAY investigated the efficacy of sexual activity-based (i.e. on demand) HIV pre-exposure prophylaxis (PrEP). Using a qualitative method, we analysed the role of adherence as one of the main elements for PrEP effectiveness and its associated determinants. Data were collected in various French ANRS-IPERGAY sites during the double-blind (2012-2014) and open-label study (2015-2016) phases, through two individual interviews per participant, collective interviews and focus groups. A total of 83 participants participated in the present study. Our analysis included 32 individual interviews (with 16 participants), 13 collective interviews (n = 45) and 8 focus groups (n = 33). We investigated adherence to on-demand pill-intake schedule, focusing especially on PrEP integration into daily life. PrEP intake was regulated through coping strategies to simplify implementation and avoid stigmatizing reactions. We considered self-care and pharmaceuticalization of prevention as specific features of sexual activity-based PrEP. As PrEP is a prophylaxis for seronegative people, it is contributing to the emergence of a new identity in the HIV field. Health-care professionals should take into account the practical implementation of PrEP schedules into daily life, assist PrEP users in personal management of pill intake and, more generally, improve adherence to the prophylaxis.

Pleasure and PrEP: Pleasure-Seeking Plays a Role in Prevention Choices and Could Lead to PrEP Initiation.

Pleasure-seeking plays a role in prevention (means choices and use), and in the sexual quality of life of men who have sex with men (MSM). Since HIV is a major threat to MSM health, new means of prevention, like pre-exposure prophylaxis (PrEP), must meet the needs of MSM to be fully efficient. Using a psychosocial approach, we examined how pleasure-seeking plays a role in participation of MSM in "ANRS-IPERGAY," a community-based trial on sexual health which included sexual on-demand PrEP. Thirteen semistructured collective interviews were conducted with 45 participants. First, we analyzed participants' search for new prevention means due to previous failures in condom use. We found that participants perceived condoms as a barrier-both materially and symbolically-to pleasure and desire, causing anxiety and stress considering sexual intercourse. Second, we explored representations and attitudes concerning pleasure within the context of PrEP. We found that PrEP allowed participants to freely choose their desired sexual positions and to better enjoy intimacy. Third, we studied the sexual quality of life for PrEP users in ANRS-IPERGAY and found an improvement. Thanks to the community-based design of the trial, this new prevention tool became a means to develop agency and empowerment for participants, not only in negotiating individual prevention but also in opposing the normative and stigmatizing discourse on sexuality and HIV. In conclusion, pleasure-seeking appears to be an essential element of sexual fulfillment that needs to be integrated as a positive notion in the study of HIV prevention.

Changes in supervised drug-injecting practices following a community-based educational intervention: A longitudinal analysis.

BACKGROUND: People who inject drugs face several health issues because of unsafe injecting practices. We aimed to evaluate changes in supervised drug-injecting practices following the implementation of a face-to-face educational intervention. METHODS: The national study ANRS-AERLI was conducted in 17 harm reduction (HR) facilities in France between 2011 and 2013. Eight offered the intervention and nine did not. We conducted a pre-post analysis focusing on injecting practices data, collected in the 8 HR facilities providing the intervention. The intervention consisted of providing face-to-face educational sessions including direct observation of injecting practices, counseling about safer injecting, and shared discussion. Injecting practices were collected following a checklist and classified as safe or unsafe. To assess changes in injecting practices, practices were compared before (at baseline) and after at least one educational session. FINDINGS: Mixed logistic models showed that the 78 participants included were more likely to improve in the following drug-use steps: setting up a clean preparation area (Adjusted Odds Ratio (AOR) = 3.4, 95% Confidence Interval (95% CI) = 1.6-7.6), hand washing (AOR = 7.2, 95% CI = 3.1-16.4), skin cleaning (AOR = 5.6, 95% CI = 2.5-12.1), choice of safe injection site (AOR = 6.5, 95% CI = 1.5-28.8) and post-injection bleeding management (AOR = 12.8, 95% CI = 5.5-29.9). Furthermore, participants were less likely to lick their needles before injecting (AOR = 8.1, 95% CI = 1.5-43.4) and to perform booting/flushing (AOR = 2.5, 95% CI = 1.2-5.3). CONCLUSIONS: The AERLI intervention seems to be effective in increasing safe drug-injecting practices.

Factors associated with perceived loss of libido in people who inject opioids: Results from a community-based survey in France.

BACKGROUND: Regular consumption of opioids exposes individuals to several side effects. One of these is a loss of libido, which has a negative impact on quality of life. We used a cross-sectional community-based survey of people who inject opioids to study factors associated with loss of libido, and more particularly the impact of the type of opioid injected. METHODS: This secondary study was conducted throughout France in 2015 and involved 514 people who inject opioids. Self-reported sociodemographic characteristics, drug consumption, injection-related data and loss of libido were collected using a brief questionnaire administered either through face-to-face interviews or online. Two different models were used to identify factors associated with loss of libido: simple logistic regression and a two-step Heckman model. RESULTS: Forty-three percent of the participants reported a loss of libido. The first model showed that filling in the questionnaire online (OR[95%CI] = 2.55[1.64;3.96]; p < 0.001), reporting that morphine sulfate (OR[95%CI] = 2.67[1.56;4.58]; p < 0.001) or methadone (OR[95%CI] = 2.50[1.13;5.56]; p = 0.030) was the opioid they injected most (versus buprenorphine), and reporting benzodiazepine use (OR[95%CI] = 1.62[1.07;2.44]; p = 0.033) were factors strongly associated with loss of libido. In the two-step, Heckman model which corrected for selection bias, along with these factors, reporting heroin as the opioid injected most was also strongly associated. CONCLUSION: Our findings showed that full-opioid agonists could have a negative impact on libido when injected regularly. Libido can improve quality of life and should be routinely discussed through counseling in prevention services with people who inject drugs.

Willingness to receive intravenous buprenorphine treatment in opioid-dependent people refractory to oral opioid maintenance treatment: results from a community-based survey in France.

BACKGROUND: Injectable opioids are an interesting option for people who inject drugs (PWID) that do not respond to oral Opioid Maintenance Treatment (OMT). To date, intravenous (IV) buprenorphine - a safer drug than full-opioid agonists in terms of overdose risk - has never been tested in a clinical trial on opioid dependence. We designed a survey to better understand the profile of PWID eligible for IV buprenorphine, and their willingness to receive it. METHODS: This cross-sectional community-based national survey was conducted through face-to-face interviews (in low-threshold and addiction care services) and online questionnaires (on https://psychoactif.org and other websites). Among the 557 participants, we selected those who were eligible for IV buprenorphine treatment (history of oral OMT, regular opioid injection) (n = 371). We used regression models to study factors associated with willingness to receive IV buprenorphine treatment among those with data on willingness (n = 353). In those who were willing (n = 294), we subsequently studied their willingness to receive daily supervised IV buprenorphine treatment. RESULTS: Among the selected 353 participants, 59% mainly injected buprenorphine, 15% heroin, 16% morphine sulfate and 10% other opioids. Eighty-three percent of the sample reported willingness to receive IV buprenorphine treatment. Factors associated with willingness were: more than 5 injection-related complications, regular buprenorphine injection, no lifetime overdose, and completion of the questionnaire online. Factors associated with unwillingness to receive daily supervised treatment were younger age (OR[IC95%]=1.04[1.01; 1.07]) and stable housing (OR[IC95%]=0.61[0.37;1.01]) while regular heroin injectors were more willing to receive daily supervision (OR[IC95%]=2.94 [1.42; 6.10]). CONCLUSIONS: PWID were very willing to receive intravenous buprenorphine as a treatment, especially those with multiple injection-related complications. In addition, our findings show that IV buprenorphine may be less acceptable to PWID who inject morphine sulfate. Young PWID and those with stable housing were unwilling to receive IV buprenorphine if daily supervision were required. This preliminary study provides useful information for the development of a clinical trial on IV buprenorphine treatment.

Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial.

OBJECTIVES: In the ANRS IPERGAY pre-exposure prophylaxis (PrEP) trial, a single dose of tenofovir disoproxil fumarate and emtricitabine was taken orally 2-24 h before sexual intercourse. A sub-study was conducted to assess the pharmacokinetics of tenofovir and emtricitabine in blood, saliva and rectal tissue following this initial oral intake. METHODS: Plasma, PBMC, saliva and rectal tissue sampling was performed over 24 h in 12 seronegative men before enrolment in the ANRS IPERGAY trial, following a single dose of 600 mg tenofovir disoproxil fumarate/400 mg emtricitabine. Ex vivo HIV infectibility of rectal biopsies was also assessed. RESULTS: The median plasma Tmax of tenofovir (median Cmax: 401 µg/L) and emtricitabine (median Cmax: 2868 µg/L) was obtained 1 h (range: 0.5-4) and 2 h (range: 1-4) after dosing, respectively. The median C24 of tenofovir and emtricitabine was 40 and 63 µg/L, respectively. The median PBMC tenofovir diphosphate and emtricitabine triphosphate levels were 12.2 and 16.7 fmol/106 cells and 2800 and 2000 fmol/106 cells at 2 and 24 h after dosing, respectively. Saliva/plasma AUC0-24 ratios were 2% and 17% for tenofovir and emtricitabine, respectively. Emtricitabine was detected in rectal tissue 30 min after dosing, whereas tenofovir was only detectable at 24 h. Ex vivo HIV infectibility assays of rectal biopsies showed partial protection after dosing (P < 0.07). DISCUSSION: A single high dose of oral tenofovir disoproxil fumarate/emtricitabine provides rapid and high blood levels of tenofovir and emtricitabine, with rapid diffusion of emtricitabine in saliva and rectal tissue.

Economic evaluation of HIV testing for men who have sex with men in community-based organizations - results from six European cities.

The non-decreasing incidence of HIV among men who have sex with men (MSM) has motivated the emergence of Community Based Voluntary Counselling and Testing (CBVCT) services specifically addressed to MSM. The CBVCT services are characterized by facilitated access and linkage to care, a staff largely constituted by voluntary peers, and private not-for-profit structures outside the formal health system institutions. Encouraging results have been measured about their effectiveness, but these favourable results may have been obtained at high costs, questioning the opportunity to expand the experience. We performed an economic evaluation of HIV testing for MSM at CBVCT services, and compared them across six European cities. We collected retrospective data for six CBVCT services from six cities (Copenhagen, Paris, Lyon, Athens, Lisbon, and Ljubljana), for the year 2014, on the number of HIV tests and HIV reactive tests, and on all expenditures to perform the testing activities. The total costs of CBVCTs varied from 54,390€ per year (Ljubljana) to 245,803€ per year (Athens). The cost per HIV test varied from to 41€ (Athens) to 113€ (Ljubljana). The cost per HIV reactive test varied from 1966€ (Athens) to 9065€ (Ljubljana). Our results show that the benefits of CBVCT services are obtained at an acceptable cost, in comparison with the literature (values, mostly from the USA, range from 1600$ to 16,985$ per HIV reactive test in clinical and non-clinical settings). This result was transversal to several European cities, highlighting that there is a common CBVCT model, the cost of which is comparable regardless of the epidemiological context and prices. The CBVCT services represent an effective and "worth it" experience, to be continued and expanded in future public health strategies towards HIV.

COBA-Cohort: a prospective cohort of HIV-negative men who have sex with men, attending community-based HIV testing services in five European countries (a study protocol).

INTRODUCTION: Community-based voluntary counselling and testing (CBVCT) services for men who have sex with men (MSM) can reach those most-at-risk and provide an environment for gay men that is likely to be non-stigmatising. Longitudinal data on the behaviour of HIV-negative MSM are scarce in Europe. The aim of this protocol, developed during the Euro HIV Early Diagnosis And Treatment (EDAT) project, is to implement a multicentre community-based cohort of HIV-negative MSM attending 15 CBVCT services in 5 European countries. RESEARCH OBJECTIVES: (1) To describe the patterns of CBVCT use, (2) to estimate HIV incidence, and to identify determinants of (3) HIV seroconversion and (4) HIV and/or sexually transmitted infection (STI) test-seeking behaviour. METHODS AND ANALYSIS: All MSM aged 18 years or over and who had a negative HIV test result are invited to participate in the COmmunity-BAsed Cohort (COBA-Cohort). Study enrolment started in February 2015, and is due to continue for at least 12 months at each study site. Follow-up frequency depends on the testing recommendations in each country (at least 1 test per year). Sociodemographic data are collected at baseline; baseline and follow-up questionnaires both gather data on attitudes and perceptions, discrimination, HIV/STI testing history, sexual behaviour, condom use, and pre- and post-exposure prophylaxis. Descriptive, exploratory and multivariate analyses will be performed to address the main research objectives of this study, using appropriate statistical tests and models. These analyses will be performed on the whole cohort data and stratified by study site or country. ETHICS AND DISSEMINATION: The study was approved by the Public Health authorities of each country where the study is being implemented. Findings from the COBA-Cohort study will be summarised in a report to the European Commission, and in leaflets to be distributed to study participants. Articles and conference abstracts will be submitted to peer-reviewed journals and conferences.

Transient damage spreading and anomalous scaling in mortar crack surfaces.

The scaling properties of a post-mortem mortar crack surface are investigated. The root mean square of the height fluctuations is found to obey anomalous scaling properties, but with three exponents, two of them characterizing the local roughness ( zeta approximately 0.79 and zetae approximately 0.41 ) and the third one driving the global roughness (zetag approximately 1.60) . The critical exponent zeta approximately 0.79 is conjectured to reflect damage screening occurring for length scales smaller than the process zone size, while the exponent zetae approximately 0.41 characterizes roughness at larger length scales, i.e., at length scales where the material can be considered as linear elastic. Finally, we argue that the global roughness exponent could be material dependent contrary to both local roughness exponents ( zeta approximately 0.8 and zetae approximately 0.4 ) which can be considered as universal.

Anomalous scaling of mortar fracture surfaces.

Scaling properties of mortar crack surfaces are studied from a mode I fracture test. Fracture surfaces initiated from a straight notch are shown to display an anomalous dynamic scaling of the crack roughness emphasizing the different crack developments between the directions parallel and perpendicular to the crack propagation direction. This anomalous roughening involves the existence of two different and independent roughness exponents. The first one, called the local roughness exponent zeta(loc), drives the self-affine scaling properties of the roughness perpendicular to crack propagation direction and can be considered as a universal roughness index zeta(loc) approximately 0.8. The second one, called the global roughness exponent, estimated to zeta approximately 1.3, is used to described the growth of the roughness at large length scales as a function of the distance to the initial notch and appears as a material-dependent parameter. We argue that the anomalous scaling of the roughness development could be an inheritance of the microcracked fracture process zone, quite large in quasibrittle materials. Finally, in the case of such an anomalous roughening, we argue that the fractal dimension appears insufficient to characterize the fracture surface morphology as a whole.

Roughness analysis of the cracked surfaces of a face centered cubic alloy.

Intergranular and transgranular fracture surfaces obtained in a face centered cubic alloy are studied using 3D maps reconstructed by scanning electron microscopy stereo imaging. The roughness exponents measured in the intergranular and transgranular surfaces, respectively, zeta = 0.83 +/- 0.05 and zeta = 0.75 +/- 0.05, are in agreement with the universal roughness value of 3D fractures. However, the slightly smaller value related to the transgranular surface could be a consequence of crystallographic transgranular zones disseminated on the surface whose roughness exponent zeta = 0.65 +/- 0.07 is close to the one usually measured on 2D fractures.

Detection of bacteria by time-resolved laser-induced breakdown spectroscopy.

A laser-induced breakdown spectroscopy technique for analyzing biological matter for the detection of biological hazards is investigated. Eight species were considered in our experiment: six bacteria and two pollens in pellet form. The experimental setup is described, then a cumulative intensity ratio is proposed as a quantitative criterion because of its linearity and reproducibility. Time-resolved laser-induced breakdown spectroscopy (TRELIBS) exhibits a good ability to differentiate among all these species, whatever the culture medium, the species or the strain. Thus we expect that TRELIBS will be a good candidate for a sensor of hazards either on surfaces or in ambient air.