California HIV/AIDS Research Program

Successful viral replication is dependent on a conducive cellular environment; thus, viruses must be sensitive to the state of their host cells. We examined the idea that an interplay between viral and cellular regulatory factors determines the switch from Kaposi's sarcoma-associated herpesvirus (KSHV) latency to lytic replication. The immediate-early gene product K-Rta is the first viral protein expressed and an essential factor in reactivation; accordingly, this viral protein is in a key position to serve as a viral sensor of cellular physiology. Our approach aimed to define a host transcription factor, i.e., host sensor, which modulates K-Rta activity on viral promoters. To this end, we developed a panel of reporter plasmids containing all 83 putative viral promoters for a comprehensive survey of the response to both K-Rta and cellular transcription factors. Interestingly, members of the NF-kappaB family were shown to be strong negative regulators of K-Rta transactivation for all but two viral promoters (Ori-RNA and K12). Recruitment of K-Rta to the ORF57 and K-bZIP promoters, but not the K12 promoter, was significantly impaired when NF-kappaB expression was induced. Many K-Rta-responsive promoters modulated by NF-kappaB contain the sequence of the RBP-Jkappa binding site, a major coactivator which anchors K-Rta to target promoters via consensus motifs which overlap with that of NF-kappaB. Gel shift assays demonstrated that NF-kappaB inhibits the binding of RBP-Jkappa and forms a complex with RBP-Jkappa. Our results support a model in which a balance between K-Rta/RBP-Jkappa and NF-kappaB activities determines KSHV reactivation. An important feature of this model is that the interplay between RBP-Jkappa and NF-kappaB on viral promoters controls viral gene expression mediated by K-Rta.

Objective: Increasing access to human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) is a high priority for the Ending the HIV Epidemic Initiative. Expanding access to PrEP and PEP through a variety of health care settings, including community pharmacies, may increase access in communities most in need. California is the first state to allow community pharmacists to furnish PrEP and PEP directly to consumers. Our objective was to assess attitudes among key stakeholders about a California policy to allow community pharmacists to furnish HIV PrEP and PEP.

Methods: We conducted a qualitative case study with key pharmacy stakeholders. Semi- structured phone interviews were audio-recorded and transcribed verbatim. We generated analytical memos for each interview and working with these analytical memos, we conducted a constant comparison across cases to identify commonalities and differences.

Results: We launched the study in October 2018 and interviewed pharmacists (n 1⁄4 7) working in a variety of settings, including retail-, clinic-, and community-based pharmacies. We also interviewed medical providers (n 1⁄4 2) working in high-volume PrEP clinics and sought input from representatives of large retail chain pharmacies (n 1⁄4 2). Overall, pharmacists and medical provider informants shared similar opinions about the central benefits as well as the key challenges related to pharmacist-delivered PrEP and PEP services. Benefits included: com- munity pharmacists are widely accessible, PrEP and PEP protocols are similar to other pre- ventative medications, policy may lead to efficiencies in the health care workforce, and community pharmacists are authorities on medication adherence. Challenges included: implementation issues may limit pharmacist involvement, and missed opportunities to di- agnose and treat other health conditions.

Conclusion: This study characterizes the types of benefits and challenges that can be expected when PrEP and PEP prescribing privileges are extended to community pharmacists. This in- formation may be useful to policymakers and other stakeholders considering legislation to permit direct prescription of PrEP and PEP by pharmacists.