ABSTRACT
The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.
ABSTRACT
Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States, particularly among people who use drugs (PWUD). PrEP research among PWUD is scarce, and the factors that impact implementation are largely unknown. Therefore, we conducted a scoping review of implementation determinants (i.e., barriers and facilitators), as well as the change methods (implementation strategies and adjunctive interventions) that have been evaluated to increase PrEP implementation and use among PWUD. We identified 32 peer-reviewed articles assessing determinants and five that evaluated change methods. Determinants were coded using the updated Consolidated Framework for Implementation Research (CFIR), which is an established framework to understand the multilevel barriers and facilitators associated with implementation. Findings indicate that most research was conducted among PrEP recipients (i.e., patients), focusing on awareness and willingness to use PrEP, with less focus on factors impacting clinicians and service delivery systems. Moreover, very few change methods have been evaluated to improve clinician adoption and adherence to CDC guidelines for PrEP provision and/or recipient uptake and adherence to PrEP. Future research is needed that focuses on factors impacting implementation from a clinician standpoint as well as innovative change methods to increase PrEP awareness, reach, adoption, and sustained adherence to guidelines. Implementation Science offers a wealth of knowledge to speed up the effort to end the HIV epidemic in the United States.
