RESUMEN

Despite the substantial national resources invested in the fight against HIV to achieve its elimination, its incidence has remained stable in recent years. In 2022, the FOPH estimated that 7% of people living with HIV in Switzerland remained undiagnosed, underlining the potential for improving screening. The aim of this article is to present the process of HIV screening and diagnosis in clinical practice, adapted to the Federal Office of Public Health (FOPH) national strategy, and including the different indications for screening, the interpretation of available tests, and the place of post-exposure prophylaxis (PEP).

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Malgré les ressources nationales considérables investies dans la lutte contre le VIH pour atteindre son élimination, son incidence est restée stable ces dernières années. En 2022, l'Office fédéral de la santé publique (OFSP) a estimé que 7 % des personnes vivant avec le VIH en Suisse n'étaient pas diagnostiquées, soulignant ainsi un potentiel d'amélioration du dépistage. L'objectif de cet article est de présenter le processus de dépistage et de diagnostic du VIH en pratique clinique, conformément à la stratégie nationale de l'OFSP. Il couvre les différentes indications au dépistage, l'interprétation des tests disponibles, ainsi que la place de la prophylaxie postexposition (PEP).

Asunto(s)

Infecciones por VIH , Tamizaje Masivo , Profilaxis Posexposición , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Tamizaje Masivo/métodos , Profilaxis Posexposición/métodos , Suiza/epidemiología , Prueba de VIH/métodos , Prueba de VIH/estadística & datos numéricos

RESUMEN

OBJECTIVES: to analyze the factors associated with university students' knowledge about HIV and preand post-exposure prophylaxis. METHODS: a cross-sectional study was conducted with 503 university students from a southern state in Brazil; data were collected using a characterization tool and a questionnaire containing 16 statements about the topic; descriptive measures and Poisson regression models with robust variance were used for analysis. RESULTS: the prevalence of adequate knowledge (i.e., scoring more than 12 correct answers) was 27.83%; students older than 24 years, enrolled in health-related courses, who had not engaged in sexual relations in the last quarter, with a history of rapid HIV testing, and who knew or had heard about the prophylaxes showed a higher likelihood of scoring more than 12 correct answers. CONCLUSIONS: generally, the knowledge of young people about HIV and its prophylaxes was found to be inadequate and influenced by sociodemographic, educational, and behavioral factors.

Asunto(s)

Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Profilaxis Posexposición , Estudiantes , Humanos , Masculino , Estudios Transversales , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Femenino , Universidades/organización & administración , Brasil , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto , Profilaxis Posexposición/métodos , Profilaxis Posexposición/estadística & datos numéricos , Adolescente , Profilaxis Pre-Exposición/métodos , Profilaxis Pre-Exposición/estadística & datos numéricos , Adulto Joven

RESUMEN

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization.

Asunto(s)

Antivirales , Gripe Humana , Profilaxis Posexposición , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antivirales/uso terapéutico , Antivirales/efectos adversos , Gripe Humana/prevención & control , Metaanálisis en Red , Profilaxis Posexposición/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano de 80 o más Años

Asunto(s)

Centers for Disease Control and Prevention, U.S. , Profilaxis Posexposición , Guías de Práctica Clínica como Asunto , Humanos , Estados Unidos , Profilaxis Posexposición/métodos , Enfermedades de Transmisión Sexual/prevención & control

RESUMEN

INTRODUCTION: Post-exposure prophylaxis (PEP) is an efficacious prevention method when initiated promptly after an HIV exposure. Yet, PEP has been underutilized, even among healthcare workers (HCWs) with occupational exposure in sites with PEP policies and procedures and access to PEP medications. It is important to understand the dynamics of uneven PEP use in what appears to be an optimal context to better protect the health and wellbeing of HCWs. METHODS: We conducted a scoping review to elucidate factors influencing HCWs' use of PEP after occupational exposure. We searched PubMed, PsychInfo and Google Scholar for peer-reviewed literature published in English from 2014 to 2022 using the terms HIV, postexposure/post-exposure prophylaxis, acceptability, healthcare workers, and values and preferences. An inductive narrative review of the resulting 53 studies identified core themes. RESULTS: Nearly all studies (96%) with various HCW types and settings occurred in low- and middle-income countries (LMICs) in Africa and Asia. Identified themes arrayed along a trajectory of PEP use experience: awareness/knowledge; acceptability; availability/access; uptake/use; adherence/completion. Across studies, awareness of PEP for HIV prevention was high, knowledge about drug regimens and healthcare facility policies was moderate to low; acceptability of PEP was moderate to high; PEP's perceived accessibility/availability was inconsistent and varied by geographic location and setting; HCWs' uptake of PEP was low, affected by not knowing how to report an exposure and being unaware of PEP availability; and adherence/completion of PEP regimens was moderate to low, impeded by side effects and a belief that completing regimens was unnecessary to avert seroconversion. HCWs consistently expressed concern about HIV stigma. DISCUSSION: Findings are limited by the inconsistent use of constructs across studies and a lack of clarity about reporting exposure events. Multi-level approaches are needed to address the interplay of individual, social and structural barriers that diminish HCWs' PEP use. Improved training, incident reporting, 24-hour access to non-stigmatizing PEP services and monitoring of adherence/completion are essential to optimizing HCWs' PEP use. CONCLUSIONS: Lessons from HCWs' experience in LMICs may inform understanding of PEP under-use among people in these settings with non-occupational exposures.

Asunto(s)

Infecciones por VIH , Personal de Salud , Exposición Profesional , Profilaxis Posexposición , Humanos , Profilaxis Posexposición/métodos , Infecciones por VIH/prevención & control , Exposición Profesional/prevención & control , África , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Asia

RESUMEN

Background: Rabies is 100% preventable by administering early and complete post exposure prophylaxis (PEP). Animal bite victims must have the knowledge and attitude necessary to seek appropriate medical care at the earliest to receive the required PEP. Objectives: The present study sought to ascertain the health-seeking behavior of animal bite victims, their knowledge and attitude regarding rabies prophylaxis, the PEP they received, and their level of compliance with the full course of anti-rabies vaccination. Methods: The study included animal bite cases that presented to the anti-rabies clinic and matched the eligibility criteria. All the required details were recorded using an internally validated structured questionnaire. All participants were followed up for six months to ensure their health conditions and compliance with the vaccination schedule. Results: Out of 1058 respondents, 57.9% were adults, with 46.6% belonging to middle socioeconomic class. 91.1% of them were informed biting animals as dogs. Before arriving at the anti-rabies clinic, 93.3% of the study subjects washed their wounds, and 62.4% visited to another health facility. Rabies knowledge was inadequate among the study participants, only 54.8% being mindful about the disease and its prevention. The compliance with the full course of antirabies vaccination was found to be 77.9%. All subjects were healthy, confirming that PEP is safe and effective. Conclusion: Regular social and behavioral change communication (SBCC) needs to be implemented with regard to health-seeking behavior.

Asunto(s)

Mordeduras y Picaduras , Profilaxis Posexposición , Rabia , Centros de Atención Terciaria , Humanos , Profilaxis Posexposición/métodos , Animales , Rabia/prevención & control , Adulto , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Perros , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/uso terapéutico , Adolescente , Adulto Joven , India , Niño , Aceptación de la Atención de Salud , Encuestas y Cuestionarios , Anciano

RESUMEN

BACKGROUND: Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine-attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. METHOD: A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. RESULTS: There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty-nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. CONCLUSIONS: Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this.

Asunto(s)

Varicela , Trasplante de Hígado , Profilaxis Posexposición , Pautas de la Práctica en Medicina , Humanos , Australia , Nueva Zelanda , Varicela/prevención & control , Profilaxis Posexposición/métodos , Niño , Pautas de la Práctica en Medicina/estadística & datos numéricos , Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/uso terapéutico , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/uso terapéutico , Encuestas y Cuestionarios

RESUMEN

Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.

Asunto(s)

Profilaxis Posexposición , Vacunas Antirrábicas , Rabia , Vacunas de ARNm , Vacunas Antirrábicas/inmunología , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/genética , Rabia/prevención & control , Animales , Humanos , Profilaxis Posexposición/métodos , Virus de la Rabia/inmunología , Virus de la Rabia/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Desarrollo de Vacunas , Perros , Ensayos Clínicos como Asunto , ARN Mensajero/genética , ARN Mensajero/inmunología

Asunto(s)

Antibacterianos , Doxiciclina , Profilaxis Posexposición , Humanos , Doxiciclina/efectos adversos , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Profilaxis Posexposición/métodos , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Enfermedades de Transmisión Sexual/prevención & control

RESUMEN

BACKGROUND: The 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. METHOD: Rabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14-28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. RESULTS: Finally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). CONCLUSIONS: The 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Profilaxis Posexposición , Vacunas Antirrábicas , Rabia , Humanos , Rabia/prevención & control , Vacunas Antirrábicas/inmunología , Vacunas Antirrábicas/administración & dosificación , Profilaxis Posexposición/métodos , China , Masculino , Inyecciones Intramusculares , Adulto , Femenino , Anticuerpos Antivirales/sangre , Estudios Transversales , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Virus de la Rabia/inmunología , Adolescente , Adulto Joven , Animales , Niño , Inmunogenicidad Vacunal , Esquemas de Inmunización

RESUMEN

OBJECTIVE: To analyze HIV Post-Exposure Prophylaxis (PEP) prescription and return for follow-up appointments. METHODS: This was a descriptive cross-sectional study using data on people who sought PEP in emergency care units (UPAs) and specialized medical services in Salvador, BA, Brazil, between January-December/2018. RESULTS: Of the 1,525 people who sought PEP at UPAs, 1,273 (83.5%) met PEP eligibility criteria, while 252 (16.5%) did not; of the eligible group, 1,166 (91.6%) had antiretrovirals prescribed, while 107 (8.4%) eligible people did not; of the total number of people with PEP prescriptions, only 226 (19.4%) returned for the first follow-up appointment, 115 (9.9%) for the second, and 33 (2.8%) for the third in order to complete the protocol. CONCLUSION: We found a significant proportion of eligible users who did not have PEP prescribed at UPAs and a significant loss of return for specialized service follow-up appointments.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Posexposición , Humanos , Estudios Transversales , Brasil , Infecciones por VIH/prevención & control , Masculino , Femenino , Profilaxis Posexposición/estadística & datos numéricos , Profilaxis Posexposición/métodos , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente , Estudios de Seguimiento , Citas y Horarios

RESUMEN

Introduction: The restrictions on face-to-face care for exposure to biological material during the COVID-19 pandemic required alternatives to maintain outpatient assistance. This study evaluated the impact of telemedicine on care and outcome indicators of a reference service for exposure to biological material during the COVID-19 pandemic. Methods: This pre- and post-study compared the effectiveness of telemedicine in the Hospital Correia Picanço in Recife (Pernambuco, Brazil) before (August 2018 to January 2019 [P1]) and during the COVID-19 pandemic (August 2020 to January 2021 [P2]). Individuals above 18 years old exposed to biological material who sought the service during P1 or P2 were included in the study. Results: A total of 4,494 cases were assessed (1,997 in P1 and 2,497 in P2), mostly because of sexual exposure (62.3%). The mean age was 32.2 ± 9.2 years, most individuals were male (64.9%), originated from Recife (56.6%), and the education level was up to 12 years (53.7%). P2 presented 43% more attendances and shorter intervals between the exposure and first attendance (51%), first testing (28%), and discharge (10%) than P1 (p < 0.05), and cases had no difference in discharge rate (p = 0.339). Cases of sexual exposure had the highest dropout rate in both periods. Conclusion: Telemedicine maintained similar outcomes to face-to-face care and improved the indicators, increasing the mean monthly attendance and reducing the time between exposure and follow-up.

Asunto(s)

COVID-19 , Profilaxis Posexposición , Telemedicina , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Femenino , Brasil/epidemiología , Adulto , Profilaxis Posexposición/métodos , SARS-CoV-2 , Pandemias/prevención & control , Persona de Mediana Edad , Adulto Joven

RESUMEN

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7-100%) versus 93.6% (95% CI 78.6-99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2-100%) and 93.1% (95% CI 77.2-99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (- 2.8, - 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI - 2.83, - 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

Asunto(s)

Antivirales , Gripe Humana , Oseltamivir , Profilaxis Posexposición , Humanos , Oseltamivir/uso terapéutico , Oseltamivir/administración & dosificación , Oseltamivir/efectos adversos , Gripe Humana/prevención & control , Masculino , Femenino , Proyectos Piloto , Profilaxis Posexposición/métodos , Niño , Antivirales/uso terapéutico , Antivirales/economía , Antivirales/efectos adversos , Antivirales/administración & dosificación , Preescolar , Lactante , Niño Hospitalizado , Resultado del Tratamiento , Adolescente

RESUMEN

INTRODUCTION: Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global population of 3rd generation or later mpox vaccines (MVA-BN, LC16m8, OrthopoxVac) compared with unvaccinated or other vaccinated states for infection, hospitalization and death. VE was stratified by 1-dose and 2-doses and post-exposure prophylaxis (PEP). METHODS: Studies were included if they measured vaccine efficacy or effectiveness in humans. Animal studies and immunogenicity studies were excluded. MEDLINE, Web of Science, Google Scholar, Embase, MedRxiv and grey literature were searched from January 1st, 1970, with the last search run on November 3, 2023 (Prospero, CRD42022345240). Risk of publication bias was assessed via funnel plots and Egger's test, and study quality via Newcastle-Ottawa scales. RESULTS: A total of 11,892 records were identified via primary search, 3,223 via citation chasing. Thirty-three studies were identified of 3rd generation vaccines, 32 of which were MVA-BN. Two additional studies were re-analysis of existing data. Most of these studies were focused on gay, bisexual, or other men who have sex with men between the ages of 18-49 in May to October of 2022. VE of 1 dose of MVA-BN was 76% (95%CI 64-88%) from twelve studies. VE of 2 doses was 82% (95%CI 72-92%) from six studies. VE of MVA-BN PEP against mpox was 20% (95%CI -24-65%) from seven studies. All VE are calculated from random effects estimates. 18/33(55%) studies were rated as poor, 3/33(9%) as fair and 12/33(36%) as good. Studies included in the meta-analysis had higher quality: 11/16 (69%) were rated as good quality. CONCLUSION: Both 1 and 2 doses of MVA-BN are highly effective at preventing mpox. Effectiveness estimates, specifically of PEP are limited by immortal time bias, predominant mode of mpox transmission, and real-world vaccine timing of administration.

Asunto(s)

Eficacia de las Vacunas , Humanos , Mpox/prevención & control , Mpox/inmunología , Profilaxis Posexposición/métodos , Vacunación/métodos , Masculino , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación

RESUMEN

In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir's in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Ritonavir , SARS-CoV-2 , Carga Viral , Humanos , SARS-CoV-2/efectos de los fármacos , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , COVID-19/prevención & control , COVID-19/virología , COVID-19/inmunología , Carga Viral/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Antivirales/farmacología , Indazoles/farmacología , Modelos Teóricos , Profilaxis Posexposición/métodos , Lactamas , Leucina , Nitrilos , Prolina

RESUMEN

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.

Asunto(s)

Accesibilidad a los Servicios de Salud , Profilaxis Posexposición , Rabia , Humanos , Rabia/prevención & control , Rabia/epidemiología , China/epidemiología , Profilaxis Posexposición/estadística & datos numéricos , Profilaxis Posexposición/métodos , Incidencia , Análisis Espacial , Disparidades en Atención de Salud/estadística & datos numéricos , Animales

RESUMEN

PURPOSE OF REVIEW: Timely postexposure prophylaxis is important after an occupational exposure. Here we review select organisms, exposure opportunities in the healthcare setting, and postexposure prophylaxis regimens. RECENT FINDINGS: Needlestick injuries pose a risk of exposure to bloodborne pathogens, such as HIV, Hepatitis B, and Hepatitis C. Risk mitigation strategies should be reexamined in light of newer vaccines and therapeutics. Increased vaccine hesitancy and vaccine denialisms may foster the re-emergence of some infections that have become extremely uncommon because of effective vaccines. With increasing occurrences of zoonotic infections and the ease of global spread as evidenced by COVID-19 and mpox, healthcare exposures must also consider risks related to emerging and re-emerging infectious diseases. SUMMARY: Early recognition and reporting of occupational exposures to pathogens with available postexposure prophylaxis is key to mitigating the risk of transmission. Providers should be able to evaluate the exposure and associated risks to provide prompt and appropriate postexposure prophylaxis.

Asunto(s)

Personal de Salud , Exposición Profesional , Profilaxis Posexposición , Humanos , Profilaxis Posexposición/métodos , Exposición Profesional/prevención & control , Lesiones por Pinchazo de Aguja/prevención & control , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , COVID-19/prevención & control , COVID-19/transmisión

RESUMEN

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Asunto(s)

Amidas , Fármacos Anti-VIH , Combinación de Medicamentos , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Profilaxis Posexposición , Piridonas , Tenofovir , Humanos , Infecciones por VIH/prevención & control , Estudios Prospectivos , Masculino , Emtricitabina/uso terapéutico , Emtricitabina/administración & dosificación , Tenofovir/uso terapéutico , Tenofovir/administración & dosificación , Tenofovir/análogos & derivados , China , Adulto , Femenino , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Amidas/uso terapéutico , Amidas/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Persona de Mediana Edad , Profilaxis Posexposición/métodos , Cumplimiento de la Medicación/estadística & datos numéricos , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Alanina/uso terapéutico , Alanina/administración & dosificación , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/administración & dosificación , Adulto Joven , Piperazinas

Asunto(s)

Doxiciclina , Profilaxis Posexposición , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual , Humanos , Doxiciclina/uso terapéutico , Doxiciclina/administración & dosificación , India , Enfermedades de Transmisión Sexual/prevención & control , Profilaxis Posexposición/métodos , Profilaxis Pre-Exposición/métodos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico

RESUMEN

BACKGROUND: SYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL. METHODS: Within 54 h of potential rabies exposure, 448 patients in two risk substrata of WHO Category III exposure were randomized to receive either 0.3 mg/kg SYN023 or 0.133 mL/kg human rabies immunoglobulin (HRIG) injected in and around the wound site(s) plus a course of rabies vaccination. Patients were followed for safety and absence of rabies for ≥ 365 days. RESULTS: GMT RVNA was higher with SYN023 throughout the 2-week post-treatment period. In the primary analysis group (n = 368), 99.4 % of SYN023 recipients versus 4.5 % of HRIG recipients had protective RVNA levels on Day 4. On Day 8, 98.1 % SYN023 versus 12.2 % HRIG recipients were protected. The SYN023:HRIG ratio of geometric mean titer of RVNA (RVNA GMTs) on Day 8 (19.42) exceeded the 10 % superiority margin (P < 0.0001) indicating higher Day 8 RVNA with SYN023. On Day 99, the SYN023:HRIG RVNA GMT ratio (0.66) was below the non-inferiority margin of 20 % (P = 0.9485) suggesting some moderation of vaccine immune response by SYN023 relative to HRIG. The ratio of percent SYN023:HRIG recipients achieving RVNA ≥ 0.5 IU/mL on Day 99 (0.98) met the non-inferiority margin of 20 % (P = 0.013) indicating anti-rabies immune response with SYN023 was non-inferior to HRIG despite this effect. There were no probable/confirmed rabies cases in any patient. Study regimens were well tolerated. CONCLUSIONS: SYN023 provided higher RVNA than HRIG soon after rabies exposure. By Day 99 post-treatment, GM RVNA with SYN023 was lower than HRIG, however, the percent of SYN023 recipients with a protective response was not inferior at this time point. No rabies cases were reported in the study. The SYN023 safety profile was acceptable. CLINICALTRIALS: gov ID: NCT03961555.

Asunto(s)

Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Profilaxis Posexposición , Vacunas Antirrábicas , Virus de la Rabia , Rabia , Humanos , Rabia/prevención & control , Rabia/inmunología , Masculino , Femenino , Adulto , Anticuerpos Antivirales/inmunología , Profilaxis Posexposición/métodos , Persona de Mediana Edad , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Método Doble Ciego , Adulto Joven , Adolescente , Virus de la Rabia/inmunología , Vacunas Antirrábicas/inmunología , Vacunas Antirrábicas/efectos adversos , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/uso terapéutico , Anciano , Niño