HIV pre-exposure prophylaxis services, provision, and delivery in the European treatment network of HIV, hepatitis and global emerging infectious diseases (NEAT ID)

Objectives: We conducted a survey to evaluate HIV pre-exposure prophylaxis (PrEP) practices in a European clinical research network on HIV, hepatitis, and global infectious diseases (NEAT ID). Methods: An online survey comprising 22 questions was sent via a secure electronic tool to the investigating physician of each of the 342 NEAT ID study centres across 15 European countries in November 2020. Results: In total, 50 sites from 12 countries responded (15% response rate). Most sites were in Western Europe, two were in Poland, and one was in Hungary. Of the responding sites, 45 provided PrEP services for a total of 27 416 PrEP users, with 1361 new PrEP initiators each month. These centres supplied PrEP for men who have sex with men (100%), people who inject drugs (84%), sex workers (84%), women (62%), and transgender women (31%). PrEP persistence after 1 year was >90%, 75%–90%, and 40%–75% in 17, 24, and 4 centres, respectively. In total, 32/45 (71%) centres reported strong community-based organization commitment at their site, and 15/45 (33%) centres developed task-shifting processes to deliver PrEP through nurses (11/15), pharmacists (5/15), and key-population peers (2/15). The biggest barriers to implementation of PrEP were low awareness of and knowledge about PrEP (47%), unwillingness to disclose sexual identity or at-risk behaviour (36%), and lack of administrative support (29%). Of the 45 centres, 32 (71%) have already been involved in PrEP research and 43 (96%) were interested in participating in such studies. Conclusions: The few NEAT ID centres that responded to the survey showed disparities in PrEP deployment and practices despite a common interest in participating in research in this field.</p

Impact sur la fonction rénale du ténofovir disoproxil utilisé en prévention des infections par le VIH ou par le virus de l'hépatite B

Number studies have shown that the prophylactic use of tenofovir disoproxil (TDF) can significantly reduce the number of new HIV and hepatitis B infections. However, the risk of TDF-associated severe renal adverse events may hamper the implementation of these new prevention strategies. This thesis aims to evaluate the impact on renal function of TDF in the setting of HIV pre-exposure prophylaxis (PrEP) and prevention of mother-to-child transmission (PMTCT) of HBV.The cohort study conducted among 3000 PrEP users followed at the Saint Louis Hospital in Paris demonstrate that the risk of acute renal failure was low and mainly concerned users with an age > 50 years and/or with an estimated glomerular filtration rate < 90mL/min at the time of prophylaxis initiation. All these users were able to continue using PrEP with a low risk of relapse. The analysis conducted in the randomized placebo-controlled Ipergay clinical trial, as well as in the ANRS-Prévenir cohort study in the Ile de France area, highlights that the use of "on-demand" HIV PrEP in men who have sex with men improved the renal safety of the prophylaxis by reducing individuals' exposure to TDF. This dosing regimen can reduce the risk of renal toxicity among individuals with risk factors of kidney injury. Data from these studies allowed the development of recommendations for renal function monitoring among PrEP users. These recommendations emphasize the need to individualize renal function monitoring and support the shift towards differentiated PrEP service delivery and models involving non-medical healthcare providers. This approach will be crucial to significantly increasing the number of PrEP users and should facilitate adherence and persistence in treatment.Concerning the PMTCT of HBV, we specifically assessed the risk of TDF-associated tubulopathy, given the harmful effect of tubular dysfunction on maternal and infant health. Using early kidney injury markers on urine samples collected in a randomized, double-blind, placebo-controlled clinical trial conducted in Thailand (iTAP), we show that TDF is not associated with a significant increase of tubulopathy and that TD can be used safely during the third trimester of pregnancy and breastfeeding. This confirms that the PMTCT of hepatitis B among women at high risk of transmission can be implemented by non-specialists in many settings.Overall, this thesis highlights that the risk of TDF-associated renal toxicity in the setting of HIV and hepatitis B prevention does not stand as a barrier to the implementation of these new preventive strategies in low-income countries that cannot perform regular monitoring of renal function.De nombreuses études montrent que l'utilisation du ténofovir disoproxil (TDF) à titre prophylactique permet de réduire très significativement le nombre de nouvelles contaminations par le VIH et par le virus de l'hépatite B. Cependant, le risque de survenue d'évènements indésirables rénaux sévères peut ralentir la mise en œuvre de ces nouvelles stratégies de prévention. Ce travail de thèse s'est donné pour objectif d'évaluer l'impact rénal du TDF utilisé dans le cadre de la prophylaxie pré-exposition (PrEP) du VIH et dans la prévention de la transmission mère-enfant (PTME) du VHB afin d'élaborer des recommandations de suivi et de surveillance de la fonction rénale sous cette prophylaxie.L'étude de cohorte menée sur les 3000 usagers de PrEP suivis à l'hôpital Saint-Louis à Paris démontre que le risque d'insuffisance rénale aigue sous TDF est faible et se concentre spécifiquement dans le groupe des utilisateurs âgés de plus de 50 ans et/ou ayant un débit de filtration glomérulaire estimé (DFGe) inférieur à 90 mL/min au moment d'initier la prophylaxie. Ces utilisateurs ont pu continuer à utiliser la PrEP, suite ou non à un arrêt temporaire, avec un faible taux de récidive de l'insuffisance rénale. L'analyse des données issues de l'essai clinique contrôlé randomisé contre placebo Ipergay et de la cohorte d'usagers de PrEP ANRS-Prévenir en Ile de France montrent que la PrEP « à la demande » chez les hommes ayant des rapports sexuels avec des hommes améliore la tolérance rénale de cette prophylaxie. Ce type de schéma intermittent peut permettre de réduire le risque de toxicité rénale chez les utilisateurs ayant des facteurs de risque d'insuffisance rénale. Les données de ces trois études combinées aux données bibliographiques permettent de suggérer des recommandations simples de suivi de la fonction rénale chez les usagers PrEP. Ces recommandations soulignent la nécessité d'individualiser la surveillance de la fonction rénale. Elles permettent d'envisager des stratégies de démédicalisation visant à augmenter significativement le nombre d'usagers en élargissant leur suivi à des professionnels de santé non médicaux tout en diversifiant les lieux d'obtention de la PrEP. Dans le cadre de la PTME de l'hépatite B, nous avons évalué spécifiquement le risque de tubulopathie maternelle, compte-tenu de l'effet potentiellement très délétère qu'une telle atteinte aurait sur la santé maternelle et infantile. En utilisant des marqueurs précoces d'atteinte tubulaire sur des prélèvements d'urines recueillis dans un essai clinique contrôlé randomisé en double insu contre placebo conduit en Thaïlande (iTAP), nous montrons que l'utilisation du TDF n'est pas associée à une augmentation significative du risque de tubulopathie et que le TDF peut être utilisé sans risque durant le troisième trimestre de grossesse et l'allaitement. Cela confirme que la PTME de l'hépatite B chez les femmes infectées à haut risque de transmission peut être mise en œuvre par des non-spécialistes dans de nombreux contextes.En conclusion, le risque de toxicité rénale lié à l'utilisation du TDF dans la prévention du VIH et de l'hépatite B ne doit pas être considéré comme un obstacle à la mise en œuvre partout dans le monde de ces stratégies de prévention très prometteuses notamment dans les pays à faibles ressources où la surveillance régulière de la fonction rénale n'est pas possible

Impact sur la fonction rénale du ténofovir disoproxil utilisé en prévention des infections par le VIH ou par le virus de l'hépatite B

Number studies have shown that the prophylactic use of tenofovir disoproxil (TDF) can significantly reduce the number of new HIV and hepatitis B infections. However, the risk of TDF-associated severe renal adverse events may hamper the implementation of these new prevention strategies. This thesis aims to evaluate the impact on renal function of TDF in the setting of HIV pre-exposure prophylaxis (PrEP) and prevention of mother-to-child transmission (PMTCT) of HBV.The cohort study conducted among 3000 PrEP users followed at the Saint Louis Hospital in Paris demonstrate that the risk of acute renal failure was low and mainly concerned users with an age > 50 years and/or with an estimated glomerular filtration rate < 90mL/min at the time of prophylaxis initiation. All these users were able to continue using PrEP with a low risk of relapse. The analysis conducted in the randomized placebo-controlled Ipergay clinical trial, as well as in the ANRS-Prévenir cohort study in the Ile de France area, highlights that the use of "on-demand" HIV PrEP in men who have sex with men improved the renal safety of the prophylaxis by reducing individuals' exposure to TDF. This dosing regimen can reduce the risk of renal toxicity among individuals with risk factors of kidney injury. Data from these studies allowed the development of recommendations for renal function monitoring among PrEP users. These recommendations emphasize the need to individualize renal function monitoring and support the shift towards differentiated PrEP service delivery and models involving non-medical healthcare providers. This approach will be crucial to significantly increasing the number of PrEP users and should facilitate adherence and persistence in treatment.Concerning the PMTCT of HBV, we specifically assessed the risk of TDF-associated tubulopathy, given the harmful effect of tubular dysfunction on maternal and infant health. Using early kidney injury markers on urine samples collected in a randomized, double-blind, placebo-controlled clinical trial conducted in Thailand (iTAP), we show that TDF is not associated with a significant increase of tubulopathy and that TD can be used safely during the third trimester of pregnancy and breastfeeding. This confirms that the PMTCT of hepatitis B among women at high risk of transmission can be implemented by non-specialists in many settings.Overall, this thesis highlights that the risk of TDF-associated renal toxicity in the setting of HIV and hepatitis B prevention does not stand as a barrier to the implementation of these new preventive strategies in low-income countries that cannot perform regular monitoring of renal function.De nombreuses études montrent que l'utilisation du ténofovir disoproxil (TDF) à titre prophylactique permet de réduire très significativement le nombre de nouvelles contaminations par le VIH et par le virus de l'hépatite B. Cependant, le risque de survenue d'évènements indésirables rénaux sévères peut ralentir la mise en œuvre de ces nouvelles stratégies de prévention. Ce travail de thèse s'est donné pour objectif d'évaluer l'impact rénal du TDF utilisé dans le cadre de la prophylaxie pré-exposition (PrEP) du VIH et dans la prévention de la transmission mère-enfant (PTME) du VHB afin d'élaborer des recommandations de suivi et de surveillance de la fonction rénale sous cette prophylaxie.L'étude de cohorte menée sur les 3000 usagers de PrEP suivis à l'hôpital Saint-Louis à Paris démontre que le risque d'insuffisance rénale aigue sous TDF est faible et se concentre spécifiquement dans le groupe des utilisateurs âgés de plus de 50 ans et/ou ayant un débit de filtration glomérulaire estimé (DFGe) inférieur à 90 mL/min au moment d'initier la prophylaxie. Ces utilisateurs ont pu continuer à utiliser la PrEP, suite ou non à un arrêt temporaire, avec un faible taux de récidive de l'insuffisance rénale. L'analyse des données issues de l'essai clinique contrôlé randomisé contre placebo Ipergay et de la cohorte d'usagers de PrEP ANRS-Prévenir en Ile de France montrent que la PrEP « à la demande » chez les hommes ayant des rapports sexuels avec des hommes améliore la tolérance rénale de cette prophylaxie. Ce type de schéma intermittent peut permettre de réduire le risque de toxicité rénale chez les utilisateurs ayant des facteurs de risque d'insuffisance rénale. Les données de ces trois études combinées aux données bibliographiques permettent de suggérer des recommandations simples de suivi de la fonction rénale chez les usagers PrEP. Ces recommandations soulignent la nécessité d'individualiser la surveillance de la fonction rénale. Elles permettent d'envisager des stratégies de démédicalisation visant à augmenter significativement le nombre d'usagers en élargissant leur suivi à des professionnels de santé non médicaux tout en diversifiant les lieux d'obtention de la PrEP. Dans le cadre de la PTME de l'hépatite B, nous avons évalué spécifiquement le risque de tubulopathie maternelle, compte-tenu de l'effet potentiellement très délétère qu'une telle atteinte aurait sur la santé maternelle et infantile. En utilisant des marqueurs précoces d'atteinte tubulaire sur des prélèvements d'urines recueillis dans un essai clinique contrôlé randomisé en double insu contre placebo conduit en Thaïlande (iTAP), nous montrons que l'utilisation du TDF n'est pas associée à une augmentation significative du risque de tubulopathie et que le TDF peut être utilisé sans risque durant le troisième trimestre de grossesse et l'allaitement. Cela confirme que la PTME de l'hépatite B chez les femmes infectées à haut risque de transmission peut être mise en œuvre par des non-spécialistes dans de nombreux contextes.En conclusion, le risque de toxicité rénale lié à l'utilisation du TDF dans la prévention du VIH et de l'hépatite B ne doit pas être considéré comme un obstacle à la mise en œuvre partout dans le monde de ces stratégies de prévention très prometteuses notamment dans les pays à faibles ressources où la surveillance régulière de la fonction rénale n'est pas possible

Impact on Renal Function of Tenofovir Disoproxil Used to Prevent HIV or Hepatitis B Infections

De nombreuses études montrent que l'utilisation du ténofovir disoproxil (TDF) à titre prophylactique permet de réduire très significativement le nombre de nouvelles contaminations par le VIH et par le virus de l'hépatite B. Cependant, le risque de survenue d'évènements indésirables rénaux sévères peut ralentir la mise en œuvre de ces nouvelles stratégies de prévention. Ce travail de thèse s'est donné pour objectif d'évaluer l'impact rénal du TDF utilisé dans le cadre de la prophylaxie pré-exposition (PrEP) du VIH et dans la prévention de la transmission mère-enfant (PTME) du VHB afin d'élaborer des recommandations de suivi et de surveillance de la fonction rénale sous cette prophylaxie.L'étude de cohorte menée sur les 3000 usagers de PrEP suivis à l'hôpital Saint-Louis à Paris démontre que le risque d'insuffisance rénale aigue sous TDF est faible et se concentre spécifiquement dans le groupe des utilisateurs âgés de plus de 50 ans et/ou ayant un débit de filtration glomérulaire estimé (DFGe) inférieur à 90 mL/min au moment d'initier la prophylaxie. Ces utilisateurs ont pu continuer à utiliser la PrEP, suite ou non à un arrêt temporaire, avec un faible taux de récidive de l'insuffisance rénale. L'analyse des données issues de l'essai clinique contrôlé randomisé contre placebo Ipergay et de la cohorte d'usagers de PrEP ANRS-Prévenir en Ile de France montrent que la PrEP « à la demande » chez les hommes ayant des rapports sexuels avec des hommes améliore la tolérance rénale de cette prophylaxie. Ce type de schéma intermittent peut permettre de réduire le risque de toxicité rénale chez les utilisateurs ayant des facteurs de risque d'insuffisance rénale. Les données de ces trois études combinées aux données bibliographiques permettent de suggérer des recommandations simples de suivi de la fonction rénale chez les usagers PrEP. Ces recommandations soulignent la nécessité d'individualiser la surveillance de la fonction rénale. Elles permettent d'envisager des stratégies de démédicalisation visant à augmenter significativement le nombre d'usagers en élargissant leur suivi à des professionnels de santé non médicaux tout en diversifiant les lieux d'obtention de la PrEP. Dans le cadre de la PTME de l'hépatite B, nous avons évalué spécifiquement le risque de tubulopathie maternelle, compte-tenu de l'effet potentiellement très délétère qu'une telle atteinte aurait sur la santé maternelle et infantile. En utilisant des marqueurs précoces d'atteinte tubulaire sur des prélèvements d'urines recueillis dans un essai clinique contrôlé randomisé en double insu contre placebo conduit en Thaïlande (iTAP), nous montrons que l'utilisation du TDF n'est pas associée à une augmentation significative du risque de tubulopathie et que le TDF peut être utilisé sans risque durant le troisième trimestre de grossesse et l'allaitement. Cela confirme que la PTME de l'hépatite B chez les femmes infectées à haut risque de transmission peut être mise en œuvre par des non-spécialistes dans de nombreux contextes.En conclusion, le risque de toxicité rénale lié à l'utilisation du TDF dans la prévention du VIH et de l'hépatite B ne doit pas être considéré comme un obstacle à la mise en œuvre partout dans le monde de ces stratégies de prévention très prometteuses notamment dans les pays à faibles ressources où la surveillance régulière de la fonction rénale n'est pas possible.Number studies have shown that the prophylactic use of tenofovir disoproxil (TDF) can significantly reduce the number of new HIV and hepatitis B infections. However, the risk of TDF-associated severe renal adverse events may hamper the implementation of these new prevention strategies. This thesis aims to evaluate the impact on renal function of TDF in the setting of HIV pre-exposure prophylaxis (PrEP) and prevention of mother-to-child transmission (PMTCT) of HBV.The cohort study conducted among 3000 PrEP users followed at the Saint Louis Hospital in Paris demonstrate that the risk of acute renal failure was low and mainly concerned users with an age > 50 years and/or with an estimated glomerular filtration rate < 90mL/min at the time of prophylaxis initiation. All these users were able to continue using PrEP with a low risk of relapse. The analysis conducted in the randomized placebo-controlled Ipergay clinical trial, as well as in the ANRS-Prévenir cohort study in the Ile de France area, highlights that the use of "on-demand" HIV PrEP in men who have sex with men improved the renal safety of the prophylaxis by reducing individuals' exposure to TDF. This dosing regimen can reduce the risk of renal toxicity among individuals with risk factors of kidney injury. Data from these studies allowed the development of recommendations for renal function monitoring among PrEP users. These recommendations emphasize the need to individualize renal function monitoring and support the shift towards differentiated PrEP service delivery and models involving non-medical healthcare providers. This approach will be crucial to significantly increasing the number of PrEP users and should facilitate adherence and persistence in treatment.Concerning the PMTCT of HBV, we specifically assessed the risk of TDF-associated tubulopathy, given the harmful effect of tubular dysfunction on maternal and infant health. Using early kidney injury markers on urine samples collected in a randomized, double-blind, placebo-controlled clinical trial conducted in Thailand (iTAP), we show that TDF is not associated with a significant increase of tubulopathy and that TD can be used safely during the third trimester of pregnancy and breastfeeding. This confirms that the PMTCT of hepatitis B among women at high risk of transmission can be implemented by non-specialists in many settings.Overall, this thesis highlights that the risk of TDF-associated renal toxicity in the setting of HIV and hepatitis B prevention does not stand as a barrier to the implementation of these new preventive strategies in low-income countries that cannot perform regular monitoring of renal function

Antibiotic susceptibilities of livestock isolates of leptospira

The authors wish to thank the consortium ‘Grupo de Trabajo Interinstitucional de Leptospirosis’ (Institut Pasteur Montevideo/UdelaR/INIA/MGAP, Uruguay) and Nicoletta Ponti for providing Leptospira strains. Thanks are also due to the technicians of the French National Reference Centre for Leptospirosis for culture and identification of strains.International audienceLeptospirosis is the most common zoonotic disease and is endemic worldwide. The antibiotic susceptibilities of Leptospira strains isolated from both humans and animals are poorly documented. This issue is particularly important for isolates from food-producing animals which are regularly exposed to antibiotic treatments. This study assessed the susceptibility of 35 leptospira strains isolated from food-producing animals of diverse geographical origins between 1936 and 2016 to the antimicrobial agents used most commonly in animals. A broth microdilution method was used to determine the susceptibilities of Leptospira strains isolated from livestock to 11 antibiotics. All isolates were susceptible to penicillin, amoxicillin, clavulanate, cephalexin, ceftriaxone, doxycycline, tetracycline, streptomycin, enrofloxacin and spectinomycin, but not polymyxin [minimum inhibitory concentration (MIC) ≥ 4 μg/L]. For tetracycline and doxycycline, the MIC was significantly higher for the recent isolates from Sardinia, Italy than for the other isolates. Antimicrobial susceptibilities were also determined with 10- and 100-fold higher inocula. High inocula significantly diminished the antibacterial effect by at least 10-fold for enrofloxacin (MIC ≥256 μg/L), streptomycin (MIC ≥16 μg/L) and tetracycline (MIC ≥32 μg/L), suggesting selection of resistant strains for high inocula. These findings contribute to the assessment of whether certain antibiotics are potentially useful for the treatment of leptospirosis, and point out the risk of failure for some antibiotics during infection with a high inoculum in both animals and humans. This study strengthens the need to detect and prevent the emergence of antimicrobial resistance of this major emerging zoonotic pathogen

Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study

International audienceBackgroundThere are few data available regarding the use of on-demand pre-exposure prophylaxis (PrEP) for HIV prevention. We aimed to assess PrEP effectiveness, adherence, and safety in adults using daily or on-demand PrEP.MethodsWe conducted a prospective observational cohort study (ANRS PREVENIR) at 26 sites in the Paris region, France. We enrolled HIV-negative adults (aged ≥18 years) at high risk of HIV infection who were starting or continuing PrEP. PrEP was prescribed as a fixed-dose combination of tenofovir disoproxil and emtricitabine (245 mg and 200 mg, respectively, per pill). PrEP could be prescribed as a daily regimen with one pill per day or, in men who have sex with men (MSM) or in transgender women who have sex with men, as an on-demand regimen following the IPERGAY dosing recommendation. At enrolment and every 3 months thereafter, participants were tested for HIV and provided information regarding the PrEP dosing regimen used. Adherence to PrEP was assessed by self-report and by tenofovir diphosphate concentrations in dried blood spots. The primary outcome of HIV-1 incidence was assessed using Poisson regression among participants who started PrEP. This study is registered with ClinicalTrials.gov, NCT03113123, and EudraCT, 2016A0157744.FindingsBetween May 3, 2017, and May 2, 2019, 3082 people were assessed for eligibility and 3065 participants were enrolled. 3056 (99·7%) of 3065 participants reported using PrEP and were included in the analyses. The median age was 36 years (IQR 29–43), 1344 (44·0%) of 3056 participants were PrEP-naive, and 3016 (98·7%) were MSM. At enrolment, 1540 (50·5%) of 3049 participants opted for daily PrEP dosing and 1509 (49·5%) opted for on-demand PrEP dosing; these proportions remained stable during follow-up. Median follow-up was 22·1 months (IQR 15·9–29·7) and incidence of study discontinuation was 17·6 participants (95% CI 16·5–18·7) per 100 person-years. At the data cutoff on Sept 30, 2020, there had been six HIV-1 seroconversions (three participants using daily PrEP and three using on-demand PrEP; all were MSM) over 5623 person-years. Overall HIV-1 incidence was 1·1 cases (95% CI 0·4–2·3) per 1000 person-years, and did not differ between participants using daily PrEP and those using on-demand PrEP (incidence rate ratio 1·00, 95% CI 0·13–7·49; p=0·99). Four participants (two using daily PrEP and two using on-demand PrEP) discontinued PrEP due to treatment-related adverse events (nausea [n=2], vomiting and diarrhoea [n=1], and lumbar pain [n=1]).InterpretationIn this study, which enrolled mainly MSM, HIV-1 incidence on PrEP was low and did not differ between participants using daily PrEP and those using on-demand PrEP. On-demand PrEP therefore represents a valid alternative to daily PrEP for MSM, providing greater choice in HIV prevention.FundingANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France.TranslationFor the French translation of the abstract see Supplementary Materials section.ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France

Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study

International audienceBackgroundThere are few data available regarding the use of on-demand pre-exposure prophylaxis (PrEP) for HIV prevention. We aimed to assess PrEP effectiveness, adherence, and safety in adults using daily or on-demand PrEP.MethodsWe conducted a prospective observational cohort study (ANRS PREVENIR) at 26 sites in the Paris region, France. We enrolled HIV-negative adults (aged ≥18 years) at high risk of HIV infection who were starting or continuing PrEP. PrEP was prescribed as a fixed-dose combination of tenofovir disoproxil and emtricitabine (245 mg and 200 mg, respectively, per pill). PrEP could be prescribed as a daily regimen with one pill per day or, in men who have sex with men (MSM) or in transgender women who have sex with men, as an on-demand regimen following the IPERGAY dosing recommendation. At enrolment and every 3 months thereafter, participants were tested for HIV and provided information regarding the PrEP dosing regimen used. Adherence to PrEP was assessed by self-report and by tenofovir diphosphate concentrations in dried blood spots. The primary outcome of HIV-1 incidence was assessed using Poisson regression among participants who started PrEP. This study is registered with ClinicalTrials.gov, NCT03113123, and EudraCT, 2016A0157744.FindingsBetween May 3, 2017, and May 2, 2019, 3082 people were assessed for eligibility and 3065 participants were enrolled. 3056 (99·7%) of 3065 participants reported using PrEP and were included in the analyses. The median age was 36 years (IQR 29–43), 1344 (44·0%) of 3056 participants were PrEP-naive, and 3016 (98·7%) were MSM. At enrolment, 1540 (50·5%) of 3049 participants opted for daily PrEP dosing and 1509 (49·5%) opted for on-demand PrEP dosing; these proportions remained stable during follow-up. Median follow-up was 22·1 months (IQR 15·9–29·7) and incidence of study discontinuation was 17·6 participants (95% CI 16·5–18·7) per 100 person-years. At the data cutoff on Sept 30, 2020, there had been six HIV-1 seroconversions (three participants using daily PrEP and three using on-demand PrEP; all were MSM) over 5623 person-years. Overall HIV-1 incidence was 1·1 cases (95% CI 0·4–2·3) per 1000 person-years, and did not differ between participants using daily PrEP and those using on-demand PrEP (incidence rate ratio 1·00, 95% CI 0·13–7·49; p=0·99). Four participants (two using daily PrEP and two using on-demand PrEP) discontinued PrEP due to treatment-related adverse events (nausea [n=2], vomiting and diarrhoea [n=1], and lumbar pain [n=1]).InterpretationIn this study, which enrolled mainly MSM, HIV-1 incidence on PrEP was low and did not differ between participants using daily PrEP and those using on-demand PrEP. On-demand PrEP therefore represents a valid alternative to daily PrEP for MSM, providing greater choice in HIV prevention.FundingANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France.TranslationFor the French translation of the abstract see Supplementary Materials section.ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France

Prevalence of Post-Acute COVID-19 Symptoms Twelve Months after Hospitalisation in Participants Retained in Follow-up: Analyses Stratified by Gender from a Large Prospective Cohort.

International audienceOBJECTIVES: Persistent post-acute COVID-19 symptom (PACS) have been reported up to 6-months (M6) after hospital discharge. Here we assessed, in the longitudinal prospective national French COVID cohort, symptoms that persisted 12-months (M12) after admission for COVID-19. METHODS: Hospitalized patients with a virologically-confirmed COVID-19 were enrolled. Follow-up was planned until M12 post-admission. Associations between persistence of ≥q3 PACS at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between January 24(th) and July 15(th) 2020, in order to allow M12 follow-up. M12 data were available for 737 participants. Median age was 61~years, 475 (64%) were men and 242/647 (37%) were admitted to ICU during the acute phase. At M12, 194/710 (27%) of participants had ≥q3 persistent PACS, mostly fatigue, dyspnea and joint pain. Among those who had a professional occupation before the acute phase 91/339 (27%) were still on sick leave at M12. Presence of ≥q3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life (HRQL) and mMRC scale 3 persistent PACS (98/253, 39% vs 96/457, 21%), depression and anxiety (18/152, 12% vs 17/268, 6% and 33/156, 21% vs 26/264, 10%, respectively), impaired physical HRQL (76/141, 54% vs 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs 171/223, 77%). CONCLUSIONS: A fourth of individuals admitted to hospital for COVID-19 still had ≥q3 persistent PACS at M12 post-discharge. Women reported more often ≥q3 persistent PACS, suffered more from anxiety and depression, and had less often returned to work than men

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

International audienceIntroduction Daily pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on‐demand PrEP with TDF/FTC in HIV‐1 uninfected men. Methods We used data from the randomized double‐blind placebo‐controlled ANRS‐IPERGAY trial and its open‐label extension conducted between February 2012 and June 2016 among HIV‐uninfected MSM starting on‐demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results During the blind phase, with a median follow‐up of 9.4 months, the mean decline slope of eGFR from baseline was −0.88 and −1.53 mL/min/1.73 m2 per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 m2 per year (p = 0.27). Including both phases, 389 participants started on‐demand TDF/FTC with a median follow‐up of 19.2 months and a mean decline of eGFR from baseline of −1.14 mL/min/1.73 m2 per year (p 40 years (p = 0.24) or hypertension (p = 0.21). There was a dose‐response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of −0.88 mL/min/1.73 m2 between >15 pills/month vs. ≤15 pills/month, p 2 to ≤10ng/mL: −0.98 mL/min/1.73 m2, >10 to ≤40ng/mL: −1.28 mL/min/1.73 m2, >40 ng/mL: −1.82 mL/min/1.73 m2, p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m2 during the OLE phase. No case of Fanconi syndrome was reported. Conclusions The renal safety of on‐demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety