About
Since its founding in 1983 by California State Legislature, the California HIV/AIDS Research Program (CHRP) has supported excellent, timely, and innovative research that is attentive to the needs of California, accelerating progress towards prevention, care and treatment for HIV/AIDS. During this time over $250M has been awarded for over 2,000 research projects.
CHRP provides start-up funds for the development of cutting edge research in California, providing critical leverage to bring in federal and private dollars to the state. A 2006 survey of California investigators found that more than five dollars in federal and other grant support was generated for every dollar invested by CHRP in California-based research.
California HIV/AIDS Research Program
California HIV/AIDS Research Program Funded Publications (196)
Current and Future PrEP Medications and Modalities: On-demand, Injectables, and Topicals
Purpose of review
Pre-exposure prophylaxis (PrEP) is a potent HIV prevention strategy, but uptake of daily oral PrEP remains low. This review covers PrEP agents currently available and agents and modalities under investigation.Recent findings
Injectable ARV preparations have high acceptability among users but are likely to require adherence to 8-week interval injections. Topical microbicide gels and vaginal rings have underperformed by intention-to-treat analyses in efficacy studies, at least in large part due to challenges with adherence and/or sustained use. However, daily oral TDF-FTC also underperformed in randomized, placebo-controlled trials compared to expectations and subsequent real-world pragmatic use. On-demand (2-1-1 dosing strategy for MSM) and injectable PrEP appear to be acceptable among participants in clinical trials. These modalities are particularly compelling alternatives for individuals who either do not want to take a daily medication (both on-demand and injectable) and/or want to take PrEP without a long commitment (on-demand). Emerging modalities such as vaginal films, microneedles, and subdermal implants have numerous advantages but are still in early stages of development.NF-kappaB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator.
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.