Design, Implementation, and Assessment Approaches Within an Advanced Human Immunodeficiency Virus (HIV) Elective Course.

Introduction: An estimated 38 million people are living with human immunodeficiency virus (HIV) worldwide. Pharmacists are well positioned to provide care to patients with HIV, but gaps in HIV education among pharmacists exist. Recognizing the need to educate and prepare future pharmacists, a 2-credit advanced HIV elective course was created for Doctor of Pharmacy students at Washington State University College of Pharmacy and Pharmaceutical Sciences in the United States, and Masters of Clinical Pharmacy students from University of Western Cape School of Pharmacy in South Africa. Methods: Course topics included diagnosis and treatment of HIV in children and adults, management of common comorbidities, pre-exposure prophylaxis, pharmacogenetic applications, and antiretroviral drug-drug interactions. Course effectiveness was evaluated using student examination results. Student perceptions were evaluated using pre- and post-course self-assessments involving abilities, confidence, and attitudes toward caring for people living with HIV. Results: Student pharmacists demonstrated competency in HIV knowledge, demonstrated skills in application to clinical-based scenarios, and reported significantly improved confidence and abilities as well as positive changes in attitudes toward people with HIV. Conclusion: This course contributed to student learning across different student cohorts in an institutional program in the United States including successful execution of distance learning and clinical application for students at a program in South Africa.

A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection.

Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir. The most recent INSTI, cabotegravir, is approved for (1) treatment of HIV infection in adults to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1 infection. Cabotegravir can be administered intramuscularly as a monthly or bi-monthly injection depending on the indication. This long-acting combination has been associated with treatment satisfaction in clinical studies and may be helpful for individuals who have difficulty taking daily oral medications. Worldwide, second generation INSTIs are preferred for treatment-naïve individuals. Advantages of these INSTIs include their high genetic barrier to resistance, limited drug-drug interactions, excellent rates of virologic suppression, and favorable tolerability. Few INSTI resistance-associated mutations have been reported in clinical trials involving dolutegravir, bictegravir and cabotegravir. Other advantages of specific INSTIs include their use in various populations such as infants and children, acute HIV infection, and individuals of childbearing potential. The most common adverse events observed in clinical studies involving INSTIs included diarrhea, nausea, insomnia, fatigue, and headache, with very low rates of treatment discontinuation versus comparator groups. The long-term clinical implications of weight gain associated with second generation INSTIs dolutegravir and bictegravir warrants further study. This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology, drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring HIV infection.

Pharmacist Comfort and Awareness of HIV and HCV Point-of-Care Testing in Community Settings.

OBJECTIVE: To address the public health concern of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission, various intrapersonal and organizational factors were identified to explore opportunities for pharmacists as part of a HIV/HCV prevention strategy. The awareness and comfort of pharmacists practicing in independent pharmacies and student pharmacists on providing HIV and HCV point-of-care (POC) tests in an urban setting were investigated. METHOD: Surveys were anonymously completed by pharmacists practicing in independent pharmacies within a 2-mile radius of our institution and student pharmacists attending our institution. Surveys were administered over a period of 10 weeks. Data were analyzed using descriptive statistics. RESULTS: A total of 119 pharmacy students and 23 practicing licensed pharmacists completed the survey. Only 21.7% of pharmacists were aware that HIV and HCV screenings are available as POC tests. Pharmacists were more likely to feel comfortable administering other POC tests and not HIV or HCV POC tests. Student pharmacists felt more comfortable than pharmacists in administering HIV and HCV POC tests and had a higher perceived level of comfort of their ability to administer these tests as licensed pharmacists. CONCLUSIONS: In this urban setting, awareness and comfort in pharmacist-provided HIV and HCV POC testing is low, however, with proper training and education, pharmacists in these community pharmacy practice settings can expand HIV and HCV screening opportunities for the community.

IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites.

UNLABELLED: In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of "big" genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in Alphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMPORTANCE: IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.

Next-generation spirobenzazepines: identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies.

We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 (2), which had advanced into preclinical development. Further structural modifications were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V(1a)/V(2) receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation.

Synthesis and evaluation of nonpeptide substituted spirobenzazepines as potent vasopressin antagonists.

A series of substituted spirobenzazepines was prepared and evaluated as V(1a) and V(2) dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown to be not only potent inhibitors of vasopressin receptors, but also have exhibited an excellent overall pharmaceutical suitability profile.

Synthesis and evaluation of spirobenzazepines as potent vasopressin receptor antagonists.

A novel series of spirobenzazepines was synthesized and evaluated for V1a and V2 receptor antagonist activity. Compounds 8b, 8i, and 8k have shown selective V1a receptor antagonist activity. Compounds 8p and 8q were shown to be dual V1a/V2 receptor antagonists.