RESUMO
The role of pharmacists in the treatment of HIV has expanded beyond medication dispensing to include a host of cost-effective, evidence-based strategies across the HIV prevention and care continuums. However, wide-scale adoption of pharmacy-based HIV prevention and treatment interventions has been slow. We conducted a systematic review to evaluate the evidence on the role of pharmacists across the HIV prevention and care continuums. Thirty-two studies were identified, most of which provided evidence of feasibility of HIV testing and efficacy of non-prescription syringe sale services in pharmacies. However, only two studies implemented an experimental design to rigorously test pharmacy-based strategies. Notably, no pharmacy-based strategies have specifically targeted the highest HIV risk populations such as black and Latinx men who have sex with men, women, or trans populations. Efficacy trials and effectiveness studies should rigorously test existing pharmacy-based strategies to build greater support for wide-scale adoption and implementation. Moreover, in order to integrate pharmacies into the strategy to end the HIV epidemic, studies are needed to ensure that pharmacy-based HIV prevention and treatment services can reach the highest risk populations.
Assuntos
Infecções por HIV , Farmácias , Minorias Sexuais e de Gênero , Continuidade da Assistência ao Paciente , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , FarmacêuticosRESUMO
INTRODUCTION: Treatment advances for metastatic breast cancer (mBC) have improved overall survival (OS) in some mBC subtypes; however, there remains no cure for mBC. Considering the use of progression-free survival (PFS) and other surrogate endpoints in clinical trials, we must understand patient perspectives on measures used to assess treatment efficacy. OBJECTIVE: To explore global patient perceptions of the concept of PFS and its potential relation to quality of life (QoL). MATERIALS AND METHODS: Virtual roundtables in Europe and the United States and interviews in Japan with breast cancer patients, patient advocates, and thought leaders. Discussions were recorded, transcribed, and analyzed thematically. RESULTS: Lengthened OS combined with no worsening or improvement in QoL remain the most important endpoints for mBC patients. Time when the disease is not progressing is meaningful to patients when coupled with improvements in QoL and no added treatment toxicity. Clinical terminology such as "PFS" is not well understood, and participants underscored the need for patient-friendly terminology to better illustrate the concept. Facets of care that patients with mBC value and that may be related to PFS include relief from cancer-related symptoms and treatment-related toxicities as well as the ability to pursue personal goals. Improved communication between patients and providers on managing treatment-related toxicities and addressing psychosocial challenges to maintain desired QoL is needed. CONCLUSION: While OS and QoL are considered the most relevant endpoints, patients also value periods of time without disease progression. Incorporation of these considerations into the design and conduct of future clinical trials in mBC, as well as HTA and reimbursement decision-making, is needed to better capture the potential value of a therapeutic innovation.
Assuntos
Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Influenza vaccines targeting the highly conserved stem of the hemagglutinin (HA) surface glycoprotein have the potential to protect against pandemic and drifted seasonal influenza viruses not covered by current vaccines. While HA stem-based immunogens derived from group 1 influenza A viruses have been shown to induce intragroup heterosubtypic protection, HA stem-specific antibody lineages originating from group 2 may be more likely to possess broad cross-group reactivity. We report the structure-guided development of mammalian-cell-expressed candidate vaccine immunogens based on influenza A virus group 2 H3 and H7 HA stem trimers displayed on self-assembling ferritin nanoparticles using an iterative, multipronged approach involving helix stabilization, loop optimization, disulfide bond addition, and side-chain repacking. These immunogens were thermostable, formed uniform and symmetric nanoparticles, were recognized by cross-group-reactive broadly neutralizing antibodies (bNAbs) with nanomolar affinity, and elicited protective, homosubtypic antibodies in mice. Importantly, several immunogens were able to activate B cells expressing inferred unmutated common ancestor (UCA) versions of cross-group-reactive human bNAbs from two multidonor classes, suggesting they could initiate elicitation of these bNAbs in humans.IMPORTANCE Current influenza vaccines are primarily strain specific, requiring annual updates, and offer minimal protection against drifted seasonal or pandemic strains. The highly conserved stem region of hemagglutinin (HA) of group 2 influenza A virus subtypes is a promising target for vaccine elicitation of broad cross-group protection against divergent strains. We used structure-guided protein engineering employing multiple protein stabilization methods simultaneously to develop group 2 HA stem-based candidate influenza A virus immunogens displayed as trimers on self-assembling nanoparticles. Characterization of antigenicity, thermostability, and particle formation confirmed structural integrity. Group 2 HA stem antigen designs were identified that, when displayed on ferritin nanoparticles, activated B cells expressing inferred unmutated common ancestor (UCA) versions of human antibody lineages associated with cross-group-reactive, broadly neutralizing antibodies (bNAbs). Immunization of mice led to protection against a lethal homosubtypic influenza virus challenge. These candidate vaccines are now being manufactured for clinical evaluation.