RESUMO
HIV prevention with antiretroviral medication in the form of pre-exposure prophylaxis (PrEP) offers a critical tool to halt the HIV pandemic. Barriers to PrEP access across drug types, formulations, and delivery systems share remarkable commonalities and are likely to be generalizable to future novel PrEP strategies. Appreciation of these barriers allows for planning earlier in the drug-development pathway rather than waiting for the demonstration of efficacy. The purpose of this article is to propose a core set of considerations that should be included in the drug-development process for future PrEP interventions. A literature synthesis of key barriers to PrEP uptake in the United States was conducted to elucidate commonalities across PrEP agents and delivery methods. Based on the published literature, we divided challenges into three main categories of structural barriers: (1) provider and clinic characteristics; (2) cost considerations; and (3) disparities and social constructs, with potential solutions provided for each. Pragmatic strategies for examining and overcoming these barriers before future PrEP regulatory approval are recommended. If these strategies are considered well before the time of commercial availability, the potential for PrEP to interrupt the HIV pandemic will be greatly enhanced.
Overcoming Barriers to Diffusion of HIV PrEP Giving antiretroviral medications to prevent acquiring HIV is called pre-exposure prophylaxis or PrEP. PrEP offers a critical tool to halt the HIV pandemic. Unfortunately, there are many barriers to PrEP access. Whether the PrEP is a pill, an injection, or other drug delivery systems not yet created, they share many common characteristics. Understanding these barriers now can help us plan earlier in the drug-development process rather than waiting for proof that the medication works. We can start overcoming barriers to PrEP access if we think of them before the drugs are developed rather than waiting until they are on the market. The purpose of this article is to propose core considerations to include in the drug-development process for future PrEP methods. The authors conducted a literature synthesis examining key barriers to PrEP uptake in the United States. The published literature was reviewed to identify commonalities across PrEP drugs and delivery methods. Based on the published literature, the authors divided challenges into three main categories: (1) provider and clinic characteristics; (2) cost considerations; and (3) disparities and social constructs. Potential solutions are provided for each. Practical strategies for examining and overcoming these barriers before future PrEP regulatory approval are recommended. If these strategies are considered before the time of commercial availability, the potential for PrEP to stop HIV will be greatly enhanced.
RESUMO
Infection is associated with activation in central autonomic nuclei involved in mediating coordinated host defense responses. Aged mice showed exaggerated sickness behavior following peripheral injection of pro-inflammatory bacterial lipopolysaccharide (LPS), but is unknown whether central autonomic network responses are concomitantly increased. To assess whether aged mice exhibit enhanced neural response to LPS, we compared neural responses using c-Fos immunohistochemistry in aged BALB/c mice (22-24 months) with those of young adult peers (3-6 months). Intraperitoneal LPS challenge induced robust expression of c-Fos protein in central autonomic regions, including catecholaminergic neurons in the pons and brainstem, as well as in barrier-associated areas including the circumventricular organs. The numbers of c-Fos positive neurons were significantly greater in the aged compared to the young adult mice. These findings show age-associated enhancement of response to inflammation in the blood-brain chemosensory interfaces as well the central autonomic pathways involved in the elaboration of sickness symptoms, which may contribute to exaggerated sickness and poorer outcomes of infectious disease in the elderly.
