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Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
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COVID-19 , Técnica Delphi , Cooperação Internacional , Saúde Pública , Humanos , COVID-19/economia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Governo , Pandemias/economia , Pandemias/prevenção & controle , Saúde Pública/economia , Saúde Pública/métodos , Organizações , Vacinas contra COVID-19 , Comunicação , Educação em Saúde , Política de Saúde , Opinião PúblicaRESUMO
Mavacamten is a FDA-approved small-molecule therapeutic designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin. It shifts myosin toward ordered off states close to the thick filament backbone. It remains elusive whether these myosin heads in the off state(s) can be recruited in response to physiological stimuli when required to boost cardiac output. We show that cardiac myosins stabilized in these off state(s) by mavacamten are recruitable by 1) Ca2+, 2) increased chronotropy [heart rate (HR)], 3) stretch, and 4) ß-adrenergic (ß-AR) stimulation, all known physiological inotropic interventions. At the molecular level, we show that Ca2+ increases myosin ATPase activity by shifting mavacamten-stabilized myosin heads from the inactive super-relaxed state to the active disordered relaxed state. At the myofilament level, both Ca2+ and passive lengthening can shift mavacamten-ordered off myosin heads from positions close to the thick filament backbone to disordered on states closer to the thin filaments. In isolated rat cardiomyocytes, increased stimulation rates enhanced shortening fraction in mavacamten-treated cells. This observation was confirmed in vivo in telemetered rats, where left-ventricular dP/dtmax, an index of inotropy, increased with HR in mavacamten-treated animals. Finally, we show that ß-AR stimulation in vivo increases left-ventricular function and stroke volume in the setting of mavacamten. Our data demonstrate that the mavacamten-promoted off states of myosin in the thick filament are at least partially activable, thus preserving cardiac reserve mechanisms.
Assuntos
Miócitos Cardíacos , Miosinas , Uracila/análogos & derivados , Animais , Ratos , Benzilaminas/farmacologia , Contração MuscularRESUMO
BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. METHODS AND FINDINGS: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days). CONCLUSIONS: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. TRIAL REGISTRATION: ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).
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Anticorpos Neutralizantes , Anticorpos Anti-HIV , Humanos , Masculino , Feminino , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Anti-HIV/sangue , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto Jovem , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Amplamente Neutralizantes/efeitos adversos , Adolescente , Injeções IntramuscularesRESUMO
BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).
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Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto JovemRESUMO
HIV genotyping is used to assess HIV susceptibility to antiretroviral drugs. The Applied Biosystems HIV-1 Genotyping Kit with Integrase (AB kit, Thermo Fisher Scientific) detects resistance-associated mutations (RAMs) in HIV protease (PR), reverse transcriptase (RT), and integrase (IN). We compared results from the AB kit with results obtained previously with the ViroSeq HIV-1 Genotyping System. DNA amplicons from the AB kit were also analyzed using next-generation sequencing (NGS). HIV RNA was extracted using the MagNA Pure 24 instrument (Roche Diagnostics; 96 plasma samples, HIV subtype B, viral load range: 530-737,741 copies/mL). FASTA files were generated from AB kit data using Exatype (Hyrax Biosciences). DNA amplicons from the AB kit were also analyzed by NGS using the Nextera XT kit (Illumina). Drug resistance was predicted using the Stanford HIV Drug Resistance Database. The mean genetic distance for sequences from ViroSeq and the AB kit was 0.02% for PR/RT and 0.04% for IN; 103 major RAMs were detected by both methods. Four additional major RAMs were detected by the AB kit only. These four major RAMs were also detected by NGS (detected in 18.1%-38.2% of NGS reads). NGS detected 27 major RAMs that were not detected with either of the Sanger sequencing-based kits. All major RAMs detected with ViroSeq were detected with the AB kit; additional RAMs were detected with the AB kit only. DNA amplicons from the AB kit can be used for NGS for more sensitive detection of RAMs.
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Farmacorresistência Viral , Técnicas de Genotipagem , Infecções por HIV , Integrase de HIV , HIV-1 , Sequenciamento de Nucleotídeos em Larga Escala , HIV-1/genética , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , HIV-1/isolamento & purificação , HIV-1/classificação , Humanos , Infecções por HIV/virologia , Técnicas de Genotipagem/métodos , Farmacorresistência Viral/genética , Integrase de HIV/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genótipo , Kit de Reagentes para Diagnóstico/normas , RNA Viral/genética , Mutação , Transcriptase Reversa do HIV/genética , Protease de HIV/genéticaRESUMO
To determine whether endorsement patterns of psychosocial symptoms revealed distinct subgroups, or latent classes, of people living with HIV who use substances (PLWH-SU), and to assess whether these classes demonstrated differential health outcomes over time. This study uses data from 801 PLWH-SU initially enrolled across 11 US hospitals during 2012-2014 and followed up in 2017. Latent class analysis included 28 psychosocial items. Regression analysis examined class membership as a predictor of viral suppression. Survival analysis examined class as a predictor of all-cause mortality. The selected model identified five unique classes. Individuals in classes characterized by more severe and more numerous psychosocial symptoms at baseline had lower likelihoods of viral suppression and survival. The study demonstrated the importance of considering patterns of overlapping psychosocial symptoms to identify subgroups of PLWH-SU and reveal their risks for adverse outcomes. Integration of primary, mental health, and substance use care is essential to address the needs of this population.
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BACKGROUND: Healthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting human immunodeficiency virus (HIV) care outcomes after healthcare transition. METHODS: We conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age, 24 years) were enrolled up to 3 months before the expected transition and were followed up to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at the baseline and at 6, 12, 18, and 24 months. RESULTS: The majority of our cohort (n = 70) was male (88.6%) and black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% confidence interval, 78%-94%) at 6 months, 76% (66%-86%) at 12 months, and 66% (55%-78%) at 18 and 24 months. Once in adult care, the proportion with viral suppression was stable (73% at baseline and 74%, 77%, 67%, and 78% at 6, 12, 18, and 24 months, respectively). CONCLUSIONS: Although most youth successfully linked to adult care, retention rates decreased over the 24-month follow-up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing this transition for youth with HIV.
Assuntos
Infecções por HIV , Transição para Assistência do Adulto , Adulto , Humanos , Masculino , Adolescente , Criança , Adulto Jovem , Georgia/epidemiologia , HIV , Estudos Prospectivos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Continuidade da Assistência ao Paciente , Carga ViralRESUMO
Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019. The authors describe the evidence supporting the value of expanded HIV testing, identify challenges in implementation, and present recommendations to address these barriers through approaches at local and federal levels to reach EHE targets.
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Epidemias , Infecções por HIV , Adulto , Humanos , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Teste de HIV , Epidemias/prevenção & controle , Programas de RastreamentoRESUMO
BACKGROUND: The TOPCARE and TEACH randomized controlled trials demonstrated the efficacy of a multi-faceted intervention to promote guideline-adherent long-term opioid therapy (LTOT) in primary care settings. Intervention components included a full-time Nurse Care Manager (NCM), an electronic registry, and academic detailing sessions. OBJECTIVE: This study sought to identify barriers, facilitators, and other issues germane to the wider implementation of this intervention. DESIGN: We conducted a nested, qualitative study at 4 primary care clinics (TOPCARE) and 2 HIV primary care clinics (TEACH), where the trials had been conducted. APPROACH: We purposively sampled primary care physicians and advanced practice providers (hereafter: PCPs) who had received the intervention. Semi-structured interviews explored perceptions of the intervention to identify unanticipated barriers to and facilitators of implementation. Interview transcripts were analyzed through iterative deductive and inductive coding exercises. KEY RESULTS: We interviewed 32 intervention participants, 30 physicians and 2 advanced practice providers, who were majority White (66%) and female (63%). Acceptability of the intervention was high, with most PCPs valuing didactic and team-based intervention elements, especially co-management of LTOT patients with the NCM. Adoption of new prescribing practices was facilitated by proximity to expertise, available behavioral health care, and the NCM's support. Most participants were enthusiastic about the intervention, though a minority voiced concerns about the appropriateness in their particular clinical environments, threats to the patient-provider relationship, or long-term sustainability. CONCLUSION: TOPCARE/TEACH participants found the intervention generally acceptable, appropriate, and easy to adopt in a variety of primary care environments, though some challenges were identified. Careful attention to the practical challenges of implementation and the professional relationships affected by the intervention may facilitate implementation and sustainability.
Assuntos
Analgésicos Opioides , Médicos , Humanos , Feminino , Analgésicos Opioides/uso terapêutico , Atenção Primária à Saúde , Padrões de Prática Médica , Medicina Baseada em EvidênciasRESUMO
[Figure: see text].
Assuntos
Diástole , Sarcômeros/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Masculino , Sarcômeros/metabolismo , Suínos , Porco MiniaturaRESUMO
The HIV/AIDS epidemic remains a major public health concern since the 1980s; untreated HIV infection has numerous consequences on quality of life. To optimize patients' health outcomes and to reduce HIV transmission, this study focused on vulnerable populations of people living with HIV (PLWH) and compared different predictive strategies for viral suppression using longitudinal or repeated measures. The four methods of predicting viral suppression are (1) including the repeated measures of each feature as predictors, (2) utilizing only the initial (baseline) value of the feature as predictor, (3) using the last observed value as the predictors and (4) using a growth curve estimated from the features to create individual-specific prediction of growth curves as features. This study suggested the individual-specific prediction of the growth curve performed the best in terms of lowest error rate on an independent set of test data.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Qualidade de Vida , Algoritmo Florestas Aleatórias , Projetos de PesquisaRESUMO
To foster retention of people living with HIV (PLWH) in HIV care in the Southern United States, we aimed to develop a stakeholder-driven mobile HIV clinic (MHC) model. From June 2019 to May 2021 we conducted a mixed-methods study: 50 surveys with out-of-care PLWH and 41 in-depth interviews with PLWH, HIV clinic staff, city officials, AIDS service organizations, and mobile clinics to examine preferences for MHC implementation. Survey data was analyzed descriptively, and interview transcripts were coded thematically. Participants recommended the MHC: (1) have nondescript exterior and HIV services nested in non-HIV care to foster confidentiality, (2) be located along public transportation and have extended hours to promote accessibility, (3) have established protocols addressing security, biosafety, and data safety; (4) provide comprehensive clinical and support services to address retention barriers; and (5) be integrated within the health system, use low-cost, diverse staffing, and establish appointment notification systems. By informing MHC design, these findings add to the toolbox of strategies that can render HIV care more accessible.
Assuntos
Infecções por HIV , HIV , Humanos , Estados Unidos , Infecções por HIV/terapia , Unidades Móveis de SaúdeRESUMO
There are inequities in HIV outcomes among Black gay, bisexual, and other sexual minority men who have sex with men (GBMSM) compared to GBMSM overall, including access to transportation to HIV care. It is unclear if the relationship between transportation and clinical outcomes extends to viral load. We assessed the relationship between transportation dependence to an HIV provider and undetectable viral load among Black and White GBMSM in Atlanta. We collected transportation and viral load information from GBMSM with HIV from 2016-2017 (n = 345). More Black than White GBMSM had a detectable viral load (25% vs. 15%) and took dependent (e.g. public) transportation (37% vs. 18%). Independent (e.g. car) transportation was associated with undetectable viral load for White GBMSM (cOR 3.61, 95% CI 1.45, 8.97) but was attenuated by income (aOR. 2.29, 95% CI 0.78, 6.71), and not associated for Black GBMSM (cOR 1.18, 95% CI 0.58, 2.24). One possible explanation for no association for Black GBMSM is that there are more competing barriers to HIV care for Black GBMSM than White GBMSM. Further investigation is needed to confirm whether 1) transportation is unimportant for Black GBMSM or 2) transportation interacts with additional factors not considered in this analysis.
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Infecções por HIV , Equidade em Saúde , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Georgia/epidemiologia , Carga Viral , Fatores Raciais , Comportamento SexualRESUMO
Persons with HIV (PWH) experience chronic pain and Post-Traumatic Stress Disorder (PTSD) at higher rates than the general population, and more often receive opioid medications to treat chronic pain. A known association exists between PTSD and substance use disorders, but less is known about the relationship between PTSD and risky opioid use among PWH taking prescribed opioid medications. In this observational study of PWH on long-term opioid medications for pain we examined associations between PTSD symptom severity based on the Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5, response range 0-80) and the following outcomes: 1) risk for opioid misuse (COMM score ≥13); 2) risky alcohol use (AUDIT score ≥8); 3) concurrent benzodiazepine prescription; and 4) morphine equivalent dose. Among 166 patients, 38 (23%) had a PCL-5 score over 38, indicating high PTSD symptom burden. Higher PCL-5 score (per 10 point difference) was associated with increased odds of opioid misuse (aOR 1.55; 95%CI: 1.31-1.83) and risky drinking (aOR: 1.28;1.07-1.52). No significant association was observed between PCL-5 score and benzodiazepine prescriptions or morphine equivalent dose. These findings suggest that when addressing alcohol and opioid use in PWH on long term opioid therapy, attention to PTSD symptoms is especially important given the higher risk for risky alcohol and opioid use among patients with this common comorbid condition.
Assuntos
Dor Crônica , Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Benzodiazepinas/efeitos adversos , Derivados da Morfina/uso terapêuticoRESUMO
The Gap Waveguide technology utilizes an Artificial Magnetic Conductor (AMC) to prevent the propagation of electromagnetic (EM) waves under certain conditions, resulting in various gap waveguide configurations. In this study, a novel combination of Gap Waveguide technology and the traditional coplanar waveguide (CPW) transmission line is introduced, analyzed, and demonstrated experimentally for the first time. This new line is referred to as GapCPW. Closed-form expressions for its characteristic impedance and effective permittivity are derived using traditional conformal mapping techniques. Eigenmode simulations using finite-element analysis are then performed to assess its low dispersion and loss characteristics. The proposed line demonstrates an effective suppression of the substrate modes in fractional bandwidths up to 90%. In addition, simulations show that a reduction of up to 20% of the dielectric loss can be achieved with respect to the traditional CPW. These features depend on the dimensions of the line. The paper concludes with the fabrication of a prototype and validation of the simulation results in the W band (75-110 GHz).
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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.
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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-2RESUMO
COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.
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Enfisema , Células-Tronco Mesenquimais , Enfisema Pulmonar , Animais , Camundongos , Elastase Pancreática , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/terapia , Células-Tronco Mesenquimais/fisiologia , Fenômenos Fisiológicos RespiratóriosRESUMO
The pandemic generated by COVID-19 forced the governments of all countries to enter into quarantine, modifying the daily coexistence among family members.
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Transtorno do Deficit de Atenção com Hiperatividade , COVID-19 , Humanos , Criança , Pandemias , Qualidade de Vida , Ansiedade/epidemiologiaRESUMO
This supplement demonstrates the profound reach of social media across several domains: improved clinical care and advocacy, data analysis, broad reach to diverse patient populations, educational access, best practices in medical education, peer review, digital strategy for individuals and institutions, and combating misinformation.
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Doenças Transmissíveis , Mídias Sociais , Doenças Transmissíveis/epidemiologia , Comunicação , HumanosRESUMO
BACKGROUND: Inflammation is associated with end-organ disease and mortality for people with human immunodeficiency virus (PWH). Ruxolitinib, a Jak 1/2 inhibitor, reduces systemic inflammation for individuals without human immunodeficiency virus (HIV) and HIV reservoir markers ex vivo. The goal of this trial was to determine safety and efficacy of ruxolitinib for PWH on antiretroviral therapy (ART). METHODS: AIDS Clinical Trials Group (ACTG) A5336 was an open-label, multisite, randomized controlled trial (RCT). Participants were randomly assigned (2:1) using centralized software to ruxolitinib (10 mg twice daily) plus stable ART for 5 weeks vs ART alone, stratified by efavirenz use. Eligible participants were suppressed on ART for ≥2 years, without comorbidities, and had >350 CD4+ T cells/µL. Primary endpoints were premature discontinuation, safety events, and change in plasma interleukin 6 (IL-6). Secondary endpoints included other measures of inflammation/immune activation and HIV reservoir. RESULTS: Sixty participants were enrolled from 16 May 2016 to 10 January 2018. Primary safety events occurred in 2.5% (1 participant) for ruxolitinib and 0% for controls (Pâ =â .67). Three participants (7.5%) prematurely discontinued ruxolitinib. By week 5, differences in IL-6 (mean fold change [FC], 0.93 vs 1.10; Pâ =â .18) and soluble CD14 (mean FC, 0.96 vs 1.08; relative FC, 0.96 [90% confidence interval {CI}, .90-1.02]) levels for ruxolitinib vs controls was observed. Ruxolitinib reduced CD4+ T cells expressing HLA-DR/CD38 (mean difference, -0.34% [90% CI, -.66% to -.12%]) and Bcl-2 (mean difference, -3.30% [90% CI, -4.72% to -1.87%]). CONCLUSIONS: In this RCT of healthy, virologically suppressed PWH on ART, ruxolitinib was well-tolerated. Baseline IL-6 levels were normal and showed no significant reduction. Ruxolitinib significantly decreased markers of immune activation and cell survival. Future studies of Jak inhibitors should target PWH with residual inflammation despite suppressive ART. CLINICAL TRIALS REGISTRATION: NCT02475655.