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1.
Nat Immunol ; 23(6): 960-970, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35654851

RESUMO

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19/prevenção & controle , Humanos , Glicoproteína da Espícula de Coronavírus
2.
Clin Infect Dis ; 77(7): 941-949, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37279602

RESUMO

BACKGROUND: Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults. METHODS: We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. RESULTS: Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA

Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , RNA Viral , Fatores de Tempo , Resultado do Tratamento
3.
JAMA ; 329(1): 63-84, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36454551

RESUMO

Importance: Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice. Objective: Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection. Evidence Review: A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered. Findings: Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential. Conclusions and Relevance: Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.


Assuntos
Antirretrovirais , Infecções por HIV , Adulto , Humanos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Antivirais/uso terapêutico , COVID-19/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Preparações Farmacêuticas , SARS-CoV-2
4.
5.
Front Public Health ; 12: 1291332, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550328

RESUMO

Background: To date, the United States (US) leads the world in the number of infections and deaths due to the Coronavirus Disease 2019 (COVID-19). Racial and ethnic disparities in COVID-19 morbidity and mortality are staggering. Age-adjusted data show that AA and Latino individuals have had higher rates of death over most of the pandemic and during surges. Project 2VIDA! is community-based participatory research (CBPR) that was developed to address individual, social, and contextual factors related to access and acceptance of the COVID-19 vaccine among African American and Latino communities in Southern California. This paper describes the study protocol and overarching objectives. Methods and design: Project 2VIDA! is a multilevel intervention that builds on the principals of CBPR and is designed to increase uptake of the COVID-19 vaccine among African American and Latino individuals (≥16 years and older) in San Diego County. The intervention was developed with a working group comprised of representatives from community and academia and centers on targeted COVID-19 individual awareness and education, linkage to medical and supportive services, COVID-19 community outreach and health promotion and offering the COVID-19 vaccine through community pop-up clinics. Discussion: Findings from 2VIDA! will provide data on the impact, feasibility, and acceptability of the intervention which are all crucial for the adaptation, refinement, and improvement of vaccine outreach interventions for COVID-19 and other vaccine preventable infectious diseases that severely impact African American and Latino communities. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05022472?term=Project+2VIDA&draw=2&rank=1, NCT05022472.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , California/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estados Unidos , Protocolos de Ensaio Clínico como Assunto
6.
Clin Infect Dis ; 50 Suppl 3: S102-7, 2010 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-20397937

RESUMO

As described elsewhere in this supplement, development of effective methods for prevention of human immunodeficiency virus (HIV) infection has proven to be more challenging than development of effective treatment for the disease. New strategies to control the HIV epidemic are urgently needed; this urgency creates interest in investigation of the possibility of using antiretroviral treatment in combination with other modalities to control the epidemic. This article summarizes current knowledge concerning prevention modalities in the context of the drivers of the HIV epidemic in specific communities, describes challenges in investigating test-and-treat strategies, and proposes research directions for addressing these challenges to investigate the impact of prevention strategies on mitigation of epidemics.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Pesquisa sobre Serviços de Saúde/métodos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos
7.
J Homosex ; 54(3): 277-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18825864

RESUMO

Under the "Don't Ask, Don't Tell, Don't Pursue, Don't Harass" Department of Defense policy, gay men and women are allowed to serve in the military, but they are not allowed to disclose their sexual orientation. This study was performed to determine the incidence of active duty military personnel seeking care at a Gay Men's Health Clinic. Nine percent of the clients, who had served between June and August 2002, were active duty U.S. Navy sailors. They all expressed fears of being discharged from the military when asked why they did not access military healthcare. The "DADTDPDH" policy breeds distrust between men who have sex with men (MSM) service-members and their healthcare provider and this ensures inadequate healthcare.


Assuntos
Centros Comunitários de Saúde/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Militares/estatística & dados numéricos , Adulto , Humanos , Masculino , Militares/legislação & jurisprudência , Política Pública , Estados Unidos
8.
JAMA Netw Open ; 6(6): e2317517, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37285160

RESUMO

This cross-sectional study analyzes the quality of ChatGPT responses to public health questions.


Assuntos
Inteligência Artificial , Saúde Pública , Humanos
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