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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.
Assuntos
Fármacos Anti-HIV , Doenças Transmissíveis Emergentes , Infecções por HIV , Hepatite A , Hepatite , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Hepatite/tratamento farmacológicoRESUMO
BACKGROUND: Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine. FINDINGS: These concerns need to be addressed before moving forward with large-scale implementation programmes. Pilot and implementation projects are required in the following areas: HIV testing algorithms, patient education, clinic procedures, protocols for switching and discontinuation, efficacy and safety in populations not included in clinical trials, and demedicalization processes. The development of models to increase the uptake of, adherence to, and persistence with and after CAB-LA injections will also be of paramount importance for success. Lessons learned from these projects will increase experience, staff expertise, and organizational and training capacities to support the roll-out of this new agent as part of HIV prevention programmes. CONCLUSION: CAB-LA has not yet achieved its full potential in HIV prevention, and strong commitment from all stakeholders is required to push CAB-LA as a game-changer in HIV response.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Piridonas/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Profilaxia Pré-Exposição/métodosRESUMO
OBJECTIVES: To assess the impact on the estimated glomerular filtration rate (eGFR) of different tenofovir disoproxil/emtricitabine dosing regimens for HIV pre-exposure prophylaxis (PrEP). PATIENTS AND METHODS: We included in the study individuals with baseline eGFRâ>â50â mL/min/1.73â m2 who initiated PrEP in the ongoing ANRS-PREVENIR PrEP cohort. We retrospectively classified PrEP users in three groups: 'on-demand' (reported at ≥75% of study visits), 'daily' (≥75% of study visits) or 'switches'. We compared the area under curve (AUC) of the eGFR variation from baseline (ΔeGFR) between groups using analysis of covariance, and assessed factors associated with a negative AUC of ΔeGFR. RESULTS: From May 2017 to October 2020, 1253 PrEP-naïve participants (98% of MSM) were included in the study with a median follow-up of 22 months. 499 (40%), 494 (39%) and 260 (21%) users were in the group daily, on-demand and switches, respectively, for a median number of pills taken per week of 6, 1.7 and 4. The mean AUC of the ΔeGFR was -1.09â mL/min/1.73â m2 in the daily PrEP group, -0.69â mL/min/1.73â m2 in the switches group and +0.18â mL/min/1.73â m2 with on-demand PrEP. In a model adjusted on baseline age and eGFR, the AUC of the ΔeGFR was significantly higher with on-demand PrEP compared to daily PrEP (Pâ=â0.037). Independent factors associated with a negative AUC of ΔeGFR were a daily PrEP regimen, a switches regimen, an ageâ>â40 years and a baseline eGFR≥90â mL/min/1.73â m². CONCLUSIONS: On-demand PrEP dosing had a smaller impact on eGFR evolution than daily PrEP, but the difference was not clinically relevant.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto , Fármacos Anti-HIV/uso terapêutico , Homossexualidade Masculina , Estudos Retrospectivos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Emtricitabina/uso terapêutico , Rim/fisiologiaRESUMO
BACKGROUND: Data evaluating the risk of proximal tubular dysfunction in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission (PMTCT) of HBV are scarce. OBJECTIVES: To assess the risk of proximal tubulopathy in pregnant women receiving tenofovir disoproxil fumarate for PMTCT of HBV. PATIENTS AND METHODS: We used urine samples collected from HBV monoinfected pregnant women who participated in a Phase III, multicentre, randomized, double-blind, placebo-controlled clinical trial assessing a tenofovir disoproxil fumarate short course from 28 weeks gestational age (28-wk-GA) to 2 months post-partum (2-months-PP) for PMTCT of HBV in Thailand. Markers of tubular dysfunction, including retinol binding protein, kidney injury molecule-1, α1-microglobuin and ß2-microglobulin, were assayed at 28- and 32-wk-GA and 2-months-PP visits. Proximal tubulopathy was defined as the presence of ≥2 of the following: tubular proteinuria, euglycaemic glycosuria and increased urinary phosphate. RESULTS: A total of 291 women participated in the study. No kidney-related adverse events were severe, and none led to tenofovir disoproxil fumarate discontinuation. At 2-months-PP, 3 of the 120 (3%) evaluated women in the tenofovir disoproxil fumarate group experienced proximal tubulopathy versus 3 of 125 (2%) in the placebo group (P = 1.00). None of the six women met the criteria for proximal tubulopathy at 12-months-PP but proteinuria persisted in three of them. No growth abnormalities were found at 1 year of age in infants born to mothers with proximal tubulopathy at 2-months-PP. CONCLUSIONS: In these HBV-infected pregnant and breastfeeding women, tenofovir disoproxil fumarate administered from 28-wk-GA to 2-months-PP was not associated with a higher risk of proximal tubulopathy.
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Vírus da Hepatite B , Complicações Infecciosas na Gravidez , Antivirais/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Tenofovir/efeitos adversosRESUMO
BACKGROUND: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations. METHODS: DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models. RESULTS: The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128-868) fmol/punch, corresponding to an estimated intake of 8-12 tablets per month (2-3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; Pâ<â0.001). In multivariate analysis, only systematic use of PrEP during SI and more frequent episodes of SI in the past 4 weeks were significantly associated with higher TFV-DP levels [OR (95% CI): 11.30 (3.62-35.33) and 1.46 (1.19-1.79), respectively; Pâ<â0.001]. CONCLUSIONS: Among participants using on-demand PrEP, estimated pill intake reached 8-12 tablets per month and was correlated with frequency and systematic use of PrEP for SI.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adenina/análogos & derivados , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Adesão à Medicação , Organofosfatos , Tenofovir/uso terapêuticoRESUMO
Pre-exposure prophylaxis (PrEP) of human immunodeficiency virus (HIV) represents the most significant breakthrough in the HIV prevention field over the past decade. PrEP is an effective strategy in preventing the transmission of HIV across all populations, providing high adherence. The current PrEP options include oral daily and on-demand tenofovir-based regimens, long-acting injections of cabotegravir, and a 1-month dapivirine vaginal ring. As a component of a multifaceted prevention approach, extensive deployment of PrEP holds the promise to significantly reduce the global HIV epidemic. Nonetheless, barriers still exist in terms of uptake, adherence, and persistence, while disparities in PrEP accessibility remain a concern.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Feminino , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , MasculinoRESUMO
BACKGROUND: We evaluated complex pre-exposure prophylaxis (PrEP) situations linked to kidney issues in a cohort of on-demand and daily PrEP users. SETTING: We conducted a single-center retrospective cohort study in France including all PrEP users who received a tenofovir disoproxil (TD)-emtricitabine (FTC) prescription between January 1, 2012 and December 31, 2019 with at least 1 creatinine measurement available before and after PrEP initiation. METHODS: A complex kidney situation (CKS) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m 2 on 2 consecutive measurements. We estimated the incidence of this event, described case management, and identified associated factors using a Cox model. RESULTS: Three thousand one hundred and fourteen individuals were included in this study. Almost all were men (99%) with a median age of 35 years, 25% had an eGFR <90 mL/minute/1.73m 2 at baseline, and 65% used on-demand PrEP. Nine users (0.29%) had a CKS at baseline; 8/9 initiated on-demand PrEP without renal function worsening after a median (interquartile range [IQR]) follow-up time of 14 months (7-31). Thirteen cases of CKS occurred during the follow-up for a 0.25 per 100 person-years incidence (95% confidence interval [CI]: [0.14; 0.45]). On-demand PrEP was used in 7/13 participants with no further episode of confirmed eGFR <60 mL/minute/1.73m 2 after a 17-month median follow-up (IQR 4-18). CKS was associated with an age ≥50 years (hazard ratio [HR] 13, 95% CI: [4-39]) or with a baseline eGFR <90 mL/minute/1.73m 2 (HR 34, 95% CI: [4-261]). 9/22 CKS were linked to high-protein intake for weight training. CONCLUSIONS: CKS were rare in our cohort. On-demand PrEP did not result in subsequent renal function worsening in these few situations.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Estudos Retrospectivos , Incidência , Emtricitabina/uso terapêutico , Rim , Homossexualidade MasculinaRESUMO
In a cohort of 72 consecutive virologically-suppressed patients with HIV-1 switching to long-acting cabotegravir and rilpivirine, we observed low cabotegravir trough concentrations 1 and 3 months after the first injection, with a significant association with no oral lead-in at 1 month [odds ratio (OR)â=â6.3 [95% confidence interval (CI) 1.7-29.5], Pâ=â0.01] and three months (ORâ=â5.6 [95% CI 1.3-29.7], Pâ=â0.03), and with high BMI at 1 month (ORâ=â1.3 [95% CI 1.1-1.6], Pâ=â0.007).
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Piridonas , Rilpivirina , Humanos , Piridonas/administração & dosagem , Rilpivirina/administração & dosagem , Rilpivirina/uso terapêutico , Rilpivirina/farmacocinética , Infecções por HIV/tratamento farmacológico , Masculino , Feminino , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , HIV-1/isolamento & purificação , Pessoa de Meia-Idade , Adulto , Substituição de Medicamentos , Administração Oral , Plasma/química , DicetopiperazinasRESUMO
Background: Mycobacterium xenopi is one of the most common pathogens responsible for non-tuberculosis mycobacteria (NTM) pulmonary diseases, which are associated with poor prognosis in immunocompromised patients. Case presentation: We report the unusual case of a 44-year-old kidney transplant recipient with multiple pulmonary nodules revealing M. xenopi pulmonary disease with atypical presentation. A three drug-regimen containing moxifloxacin, ethambutol and azithromycin was prescribed, with careful monitoring of the immunosuppressive therapy. The outcome was favorable. Discussion and conclusion: Although infrequent in kidney transplant recipients, NTM can cause pulmonary infection several years after transplantation. Treatment of M. xenopi infection relies on a multidrug regimen with at least 3 antimycobacterial drugs. Drug-drug interactions between immunosuppressive treatments and rifamycins require careful dose adjustment and monitoring to avoid graft rejection.
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Black cisgender women (hereafter referred to as "women") have disproportionately high rates of HIV infection yet low rates of pre-exposure prophylaxis (PrEP) utilization. Barriers to PrEP uptake exist at the system, provider, and individual/client level. To learn how existing training and advertising can be adapted to address race- and sex-based gaps within PrEP service delivery, we conducted focus groups with providers and Black women. Participants were recruited at three health care organizations in the Midwest and South, screened for eligibility, and consented verbally. Focus groups occurred from August 2022 to February 2023. Women were asked about their knowledge and thoughts on PrEP. Providers were asked about factors influencing their decision-making about PrEP. A codebook was developed based on the Consolidated Framework for Implementation Research. Transcripts were coded using the Stanford Lightning Report Method. We completed four focus groups with 10 providers and 9 focus groups with 25 women. Three major themes emerged: (1) low comfort level and limited cultural sensitivity/competency among providers discussing HIV risk and PrEP with Black women, (2) women's concerns about PrEP's side effects and safety during pregnancy, and (3) lack of Black women representation in PrEP advertisement/educational materials. In addition, women in the South reported general medical mistrust and specific misconceptions about PrEP. PrEP trainings for providers need detailed information about the safety of PrEP for women and should include role-playing to enhance cultural competency. Likewise, PrEP advertisements/materials should incorporate information regarding side effects and images/experiences of Black women to increase PrEP awareness and uptake among this population. Clinical Trial Registration Number: NCT05626452.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Feminino , Publicidade , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Negro ou Afro-Americano , Confiança , Fármacos Anti-HIV/uso terapêuticoRESUMO
OBJECTIVES: Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. METHODS: Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. RESULTS: We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale <57. Compared with men, women more often reported presence of ≥3 persistent PACSs (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 health-related quality of life (76/141, 54% vs. 120/261, 46%). Women had less often returned to work than men (77/116, 66% vs. 171/223, 77%). CONCLUSIONS: One fourth of the individuals admitted to hospital for COVID-19 still had ≥3 persistent PACSs at M12 post-discharge. Women reported more often ≥3 persistent PACSs, suffered more from anxiety and depression and had less often returned to work than men.
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COVID-19 , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , COVID-19/epidemiologia , SARS-CoV-2 , Prevalência , Qualidade de Vida , Estudos Prospectivos , Assistência ao Convalescente , Alta do Paciente , HospitalizaçãoRESUMO
PURPOSE OF REVIEW: This review focuses on the safety of oral tenofovir disoproxil and emtricitabine (FTC) combination for HIV preexposure prophylaxis (PrEP) in adults. RECENT FINDINGS: Gastrointestinal adverse events are common after treatment initiation but usually resolve within weeks. Although clinical trials did not report an increased risk of serious renal adverse events or tubulopathy, meta-analyses suggest that tenofovir disoproxil -FTC is associated with a slight but non-clinically relevant decline in estimated glomerular filtration rate (eGFR). A decline to less than 60âmL/min remains a rare event, which mainly occurs in users with an age >50âyears or a baseline creatinine clearance < 90âmL/min. Similarly, a slight reduction in bone mineral density (BMD) was observed in clinical trials, but it did not result in an increased risk of bone fracture. BMD reduction and eGFR decline tend to resolve after treatment discontinuation. No drug interaction with contraception has been reported in women and no safety signal emerged in pregnant and breastfeeding women. SUMMARY: Oral tenofovir disoproxil-FTC for HIV PrEP appears safe and well tolerated for most individuals. This supports demedicalization strategies aiming at increasing the number of PrEP users.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Pessoa de Meia-Idade , Tenofovir/uso terapêuticoRESUMO
BACKGROUND: There 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. METHODS: We 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. FINDINGS: Between 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]). INTERPRETATION: In 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. FUNDING: ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Adesão à Medicação , Estudos Prospectivos , TenofovirRESUMO
Pre-exposure prophylaxis (PrEP) has proven to be a highly effective and safe way to prevent HIV infection. Seroconversion and primary HIV infection are exceptional if adherence to PrEP is good. However, primary HIV infection while using PrEP can occur, albeit rarely, and HIV drug resistance might develop. Furthermore, the scope of PrEP is expected to expand, and clinicians might face potential seroconversions and primary HIV infection in patients starting or taking PrEP. The characteristics of primary HIV infection in users of PrEP are poorly described. PrEP users present a lower viral load peak during primary HIV infection and, frequently, fewer symptoms than individuals not exposed to PrEP. Additionally, PrEP prolongs the stages of seroconversion, thus potentially complicating diagnosis of primary HIV infection. Drug resistance is rare, occurring mostly when PrEP is initiated in undiagnosed patients who are at an extremely early stage of infection, in whom detection of HIV-RNA was not used to rule out HIV infection. Therefore, careful exclusion of primary HIV infection before starting PrEP is crucial. In patients presenting with primary HIV infection while on PrEP, a drug with a high genetic barrier (or even two) should be added to tenofovir disoproxil fumarate-emtricitabine until test results for resistance are available.
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Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Emtricitabina/uso terapêutico , Soropositividade para HIV , HIV-1/efeitos dos fármacos , Humanos , Tenofovir/uso terapêutico , Carga Viral/efeitos dos fármacosRESUMO
INTRODUCTION: 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 < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m2 (p = 0.44), age >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 < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to ≤2 ng/mL: >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.
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Fármacos Anti-HIV/farmacologia , Emtricitabina/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Tenofovir/farmacologia , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Método Duplo-Cego , Emtricitabina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Minorias Sexuais e de Gênero , Tenofovir/uso terapêutico , Adulto JovemRESUMO
OBJECTIVES: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight. METHODS: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen. RESULTS: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, Pâ¯=â¯0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for <48â¯kg patients and HR 1.64, 95% CI 1.20-2.25 for 48-59.9â¯kg patients, compared to those with >60â¯kg, P < 0.001) and hypertension (HR 4.03, 95% CI 2.0-8.0, P < 0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (Pâ¯=â¯0.27). CONCLUSIONS: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Tenofovir/efeitos adversos , Zidovudina/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Povo Asiático , Peso Corporal , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Tailândia , Zidovudina/administração & dosagemRESUMO
The aim of our study was to describe the clinical features, the etiologies, and the factors associated with poor outcome of encephalitis in French Guiana. Our study was retrospective, including all cases of encephalitis hospitalized in the Cayenne General Hospital, from January 2007 to July 2017. Patients were included through the 2013 encephalitis consortium criteria and the outcome was evaluated using the Glasgow outcome scale at 3 months from the diagnosis of encephalitis. We included 108 patients, giving an approximate incidence rate of four cases/100,000 inhabitants/year. The origin of the encephalitis was diagnosed in 81 cases (75%), and 72 of them (66.7%) were from an infectious origin. The most common infectious causes were Cryptococcus sp. (18.5%) independently of the immune status, Toxoplasma gondii (13.9%), and Streptococcus pneumoniae (5.5%). In the follow-up, 48 patients (46.6%) had poor outcome. Independent risk factors associated with poor outcome at 3 months were "coming from inside area of the region" (P = 0.036, odds ratio [OR] = 4.19; CI 95% = 1.09-16.06), need for mechanical ventilation (P = 0.002, OR = 5.92; CI 95% = 1.95-17.95), and age ≥ 65 years (P = 0.049, OR = 3.99; CI 95% = 1.01-15.89). The most identified cause of encephalitis in French Guiana was Cryptococcus. The shape of the local epidemiology highlights the original infectious situation with some local specific pathogens.
Assuntos
Criptococose/epidemiologia , Encefalite/epidemiologia , Meningoencefalite/epidemiologia , Infecções Pneumocócicas/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus/isolamento & purificação , Cryptococcus/patogenicidade , Encefalite/microbiologia , Encefalite/mortalidade , Encefalite/parasitologia , Feminino , Guiana Francesa/epidemiologia , Escala de Resultado de Glasgow , Humanos , Incidência , Masculino , Meningoencefalite/microbiologia , Meningoencefalite/mortalidade , Meningoencefalite/parasitologia , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Respiração Artificial , Estudos Retrospectivos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade , Análise de Sobrevida , Toxoplasma/isolamento & purificação , Toxoplasma/patogenicidade , Toxoplasmose/mortalidade , Toxoplasmose/parasitologiaRESUMO
Leptospirosis 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.