Tuberculosis (TB) and human immunodeficiency virus (HIV) represent a significant burden of disease on a global scale. Despite improvements in the global epidemic status, largely facilitated by increased access to pharmacotherapeutic interventions, slow progress in the development of new clinical interventions coupled with growing antimicrobial resistance to existing therapies represents a global health crisis. There is an urgent need to expand the armamentarium of TB and HIV therapeutic strategies. Host mediated immune responses represent an untapped reservoir of novel approaches for TB and HIV. Antimicrobial peptides (AMPs) are an essential aspect of the immune system. Cathelicidins and defensins AMPs have been studied for their potential applications in TB and HIV therapeutic interventions. Genetic polymorphism across different population groups may affect endogenous expression or activity of AMPs, potentially influencing therapeutic outcomes. However, certain genetic polymorphisms in autophagy pathways may alter the downstream effects of nano-delivery of cathelicidin. On the other hand, certain genetic polymorphisms in beta-defensins may provide a protective role in reducing HIV-1 mother-to-child-transmission. Pharmaceutical development of cathelicidins and defensins is disadvantaged with complex challenges. Nanoparticle formulations improve pharmacokinetics and biocompatibility while facilitating targeted drug delivery, potentially minimising the risk of immunogenicity or non-specific haemolytic activity. This review aims to explore the potential viability of using cathelicidins and defensins as novel pharmacotherapy in the management of TB and HIV, highlight potential pharmacogenomic implications in host mediated immunity and AMP therapeutic applications, as well as propose novel drug delivery strategies represented by nanomedicine for AMPs.

Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome.

Introduction: Minority groups are underrepresented in pharmacogenomics (PGx) research. Recent sub-analysis of CYP-GUIDES showed reduced length of stay (LOS) in depressed patients with CYP2D6 sub-functional status. Our primary objective was to determine whether PGx guided (G) versus standard treatment (S) influenced LOS among different race/ethnic groups. Secondary objectives included prevalence of drug-gene interactions (DGIs) and readmission rates (RAR).Methods: Retrospective sub-analysis of CYP-GUIDES data comprising CYP2D6 phenotypes was reclassified using standardized CYP2D6 genotype to phenotype recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG). The Mann-Whitney test was used to determine differences in LOS between groups G and S and Kruskal Wallis test to compare LOS among different race/ethnic groups. Logistic regression was used to determine covariates associated with RAR.Results: This study included 1,459 patients with 67.3% in G group (n = 982). The majority of patients were White (57.5%), followed by Latinos (25.6%) and Blacks (12.3%). Although there were no differences in LOS between G and S groups, Latinos had significant shorter LOS than Whites (p = 0.002). LOS was significantly reduced by 5.6 days in poor metabolizers in group G compared to S (p = 0.002). The proportion of supra functional and ultra-rapid metabolizers (UMs) were 6 and 20.3% using CYP-GUIDES and CPIC/DPWG definitions, respectively. Prevalence of DGIs was 40% with significantly fewer DGIs in Blacks (p < 0.001). Race/ethnicity was significantly associated with RAR (aOR 1.30; p = 0.003).Conclusion: A greater number of patients were classified as CYP2D6 UMs using CPIC/DPWG definitions as compared to CYP-GUIDES definitions. This finding may have clinical implications for using psychotropics metabolized by CYP2D6.

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.

Background: Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status. Objective: To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks. Methods: Thirty-four treatment-naïve HIV individuals initiating lopinavir/ritonavir monotherapy and receiving clinical care from private practice in Houston, Texas, were included. Serum 25-hydroxyvitamin D levels from stored plasma samples collected from IMANI-2 pilot study at both baseline and 48 weeks were analyzed using LC-MS assays. Mean 25(OH)D at baseline and 48 weeks were compared using paired t-tests. Linear regression analysis was used to evaluate factors associated with changes in 25(OH)D. Logistic regression analyses were used to determine the effect of vitamin D status and covariates on CD4 cell count recovery. Results: Mean 25(OH)D was significantly higher at 48 weeks (26.3 ng/mL (SD + 14.9); p=0.0003) compared to baseline (19.8 ng/mL (SD +12.1), with fewer individuals having vitamin D deficiency (41.2%) and severe deficiency (11.8%). Both body mass index and baseline CD4 cell count were significant independent covariates associated with 25(OH)D changes over 48 weeks. Baseline vitamin D status did not affect CD4 cell count recovery. However, in a 24-week multivariate analysis, current tobacco use was significantly associated with a decreased odds of CD4 cell count recovery (AOR 0.106, 95% CI 0.018-0.606; p=0.012). Conclusion: Individuals treated with lopinavir/ritonavir monotherapy had significantly higher 25(OH)D after 48 weeks. Current tobacco users had significantly diminished CD4 cell count recovery after starting treatment, warranting further clinical investigation.

Background: The United States (U.S.) Centres for Disease Control and Prevention estimated that over one million U.S. adults could benefit from human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP), but only 90,000 PrEP prescriptions are being filled annually. Pharmacists are well-positioned to offer PrEP, but a lack of awareness and knowledge about HIV PrEP has been a limitation. This study was designed to evaluate the knowledge, confidence, and perceptions of pharmacy students towards the use of HIV PrEP in high-risk populations before and after receiving a PrEP and PEP module in a two-credit hour Advanced HIV Elective course. Methods: Faculty in an Advanced HIV Elective course implemented a PrEP module and evaluated the impact on pharmacy student knowledge, confidence, and attitudes in 2020. Results: Participation led to a significant increase in student pharmacist confidence in offering patient education regarding the use of PrEP, risk mitigation counselling, accurately ordering labs, monitoring patients taking PrEP, and HIV medication therapy management. Additionally, HIV education shows decreased stigma and negative attitudes towards high-risk individuals. Conclusion: Integration of a PrEP module increased student pharmacist knowledge and confidence in providing PrEP services while reducing stigma towards those with HIV.