Addressing racial inequality and its effects on vaccination rate: A trial comparing a pharmacist and peer educational program (MOTIVATE) in diverse older adults.

BACKGROUND: The mortality, morbidity, health care utilization, and cost attributable to vaccine-preventable diseases are substantial for those aged 50 years and older. Although vaccination is the most cost-effective strategy to prevent common infectious diseases in older adults, vaccination rates remain below US Centers for Disease Control and Prevention benchmarks, especially among racial minorities. Historical mistrust, structural racism within the US medical system, and misinformation contributed to lower immunization rates among minorities, especially Black Americans. To address the critical need to increase knowledge and trust in vaccination, 2 community-based educational interventions were tested: a pharmacist-led didactic session (PHARM) and a peer-led educational workshop (PEER). OBJECTIVE: To determine and compare the effectiveness and costs of PEER and PHARM community-based education models in improving knowledge and trust in vaccinations. METHODS: The Motivating Older adults to Trust Information about Vaccines And Their Effects (MOTIVATE) study was a cluster-randomized trial conducted in the greater Delaware Valley Region sites from 2017 to 2020. The included sites (7 senior centers, 3 housing units, 1 church, and 1 neighborhood family center) predominantly served Black communities. Participants were randomized to either PHARM or PEER sessions covering influenza, pneumococcal disease, herpes zoster, and beliefs related to vaccines. Peer leaders facilitated smaller workshops (5-10 participants), whereas pharmacists conducted larger didactic lectures with 15-43 participants. Outcomes were captured through a self-administered survey at baseline, postprogram, and 1 month after the program. Intervention costs were measured in 2017 US dollars. RESULTS: 287 participants were included. Their mean age was 74.5 years (SD = 8.94), 80.5% were women, 64.2% were Black, and 48.1% completed some college. Knowledge scores within groups for all 3 diseases significantly increased postprogram for both PEER and PHARM and were sustained at 1 month. Between-group knowledge differences were significant only for influenza (PEER participants had significantly larger improvement vs PHARM). Vaccination trust significantly increased in both groups. Total program costs were $11,411 for PEER and $5,104 for PHARM. CONCLUSIONS: Both interventions significantly improved knowledge and trust toward vaccination and retained their effect 1 month after the program. The 2 effective community-based education models should be expanded to ensure timely and trusted information is available to educate older adults about vaccine-preventable diseases. Further research is encouraged to assess the long-term cost-effectiveness of these models' utilization on a larger scale. DISCLOSURES: Dr Schafer is an employee of Merck; however, at the time of the project, he was a professor at Thomas Jefferson University. The other authors have no conflicts of interest to disclose. This study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. The opinions expressed in this article are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. The sponsor played no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the article. Study Registration Number: NCT03239665.

Weight changes in patients with sustained viral suppression switching tenofovir disoproxil fumarate to tenofovir alafenamide.

OBJECTIVE: Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear. METHODS: This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values >200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch. RESULTS: In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models. CONCLUSIONS: Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.

Patients Living With HIV Are Less Likely to Receive Appropriate Statin Therapy for Cardiovascular Disease Risk Reduction.

BACKGROUND: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. OBJECTIVES: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. METHODS: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. RESULTS: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. CONCLUSION: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.

Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment-Experienced Patients.

BACKGROUND: Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool's HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients' preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired t test analyzed changes in total DDI scores following ART switches, and linear regression examined factors contributing to DDI score reductions. RESULTS: Among 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, -1.1 to -0.8) after patients switched to BIC/FTC/TAF (P < .0001). After adjusting for demographics, baseline ART, and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions, and conditions requiring hormonal therapy. CONCLUSIONS: Treatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF.

Exploring beliefs about pneumococcal vaccination in a predominantly older African American population: the Pharmacists' Pneumonia Prevention Program (PPPP).

Objectives: To assess the association of the Pharmacists' Pneumonia Prevention Program (PPPP) with changes in beliefs related to pneumonia vaccination (PV) in a predominately older African American population.Methods: PPPP was an educational intervention delivered using a senior center model of care consisting of a formal pharmacist presentation, live skit, small group action planning, and optional PV. A 15-item instrument assessed participants' beliefs at baseline, post-test, and three months across four domains: pharmacists and pharmacies, vaccination, pneumococcal disease, and physicians. Friedman tests and pairwise Wilcoxon signed rank tests were used to determine the statistical significance of the mean change in belief responses across timepoints.Results: 190 older adults participated; the sample was majority female (76.3%) and African American (80.5%), and had a mean age of 74.3 years. Statistically significant improvements in beliefs at post-test were observed in the following domains: pharmacists and pharmacies, vaccination, and the pneumococcal disease; however, some of these gains were incompletely sustained at three months.Conclusion: PPPP positively impacted beliefs post-program regarding the pneumococcal disease, pharmacists and pharmacies, and vaccination; however, sustained efforts may be needed to reinforce these gains.Policy implications: Support for pharmacist educational services in senior centers should be considered.

The Incidence and Severity of Drug Interactions Before and After Antiretroviral Therapy Simplification in Treatment-Experienced Patients With HIV Infection.

Background: Current guidelines advocate for antiretroviral therapy (ART) simplification in patients on complicated regimens. Simplifying ART improves patient adherence and quality of life, but changes in drug interactions (DIs) are uncertain. Objective: This study assessed changes in DIs following ART simplification in patients with HIV. Methods: This was an observational, retrospective cohort study of patients attending an urban HIV clinic. Patients were included if they had ART simplification (a decreased number of daily tablets) and ≥1 concomitant medication (CM). Total DI scores were generated for each patient pre-ART simplification and post-ART simplification using an online DI database. Each ART-CM pair labeled as "do not co-administer" was given a score of 2, "potential interaction" a score of 1, or "no interaction" a score of 0. Differences in total DI scores following simplification were analyzed with a Wilcoxon Signed-Rank test. Predictors of DI score reductions were examined with linear regression. Results: A total of 99 patients were included. Their median age was 54 years, and 79% were male. The median durations of HIV infection and ART were 16 and 10 years, respectively. Patients were receiving an average of 4.5 CMs. Median interaction scores presimplification and postsimplification were 3 (interquartile range [IQR], 1-6) and 1 (IQR, 0-2) respectively (P < 0.001). Predictors of score reductions were the patient's number of CMs, discontinuing a protease inhibitor, and switching to a dolutegravir-based regimen. Conclusion and Relevance: ART simplification decreased the incidence of DIs in this analysis of patients with advanced age who had ART experience and polypharmacy.

Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide.

BACKGROUND: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown. METHODS: This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values <200 copies/mL before a TAF switch were included. Body weight, BMI, cholesterol, and ASCVD risk score were collected for the year before and after the switch. Pre- and postswitch values were compared with the Wilcoxon signed-rank test. Changes in BMI and ASCVD scores were modeled using generalized estimating equations regression. RESULTS: One hundred ten patients were included. In unadjusted analyses, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD risk score in the year after switching from TDF to TAF (each P ≤ .01). In regression models, switching from TDF to TAF was associated with a 0.45 kg/m2 increase in BMI (95% confidence interval [CI], 0.14-0.76) and a 13% increase in ASCVD risk score (95% CI, 4%-23%). CONCLUSIONS: We observed significant BMI and ASCVD score increases in PWH 1 year after switching from TDF to TAF. The mechanism of changes is unclear and requires additional study.

Knowledge, Activation, and Costs of the Pharmacists' Pneumonia Prevention Program (PPPP): A Novel Senior Center Model to Promote Vaccination.

BACKGROUND: Vaccination is the best way to prevent pneumococcal disease (PD), but 40% of older adults remain unvaccinated nationwide, with even greater nonvaccination rates among African Americans (AAs). Prior studies suggest that insufficient knowledge contributes to low vaccination rates. The Pharmacists' Pneumonia Prevention Program (PPPP) was designed to improve older adults' knowledge about PD and pneumococcal vaccination (PV). OBJECTIVE: To measure PPPP's effect on knowledge and activation in a predominantly AA population and determine program costs. METHODS: PPPP uses a senior center model with a pharmacist presentation, actors' skit, and small-group action planning. Knowledge about PD risk, transmission, symptoms, and PV side effects was assessed at baseline (BL), postintervention (PT), and 3 months (M3) and analyzed using an intention-to-treat (ITT) approach. Actions taken (got vaccinated, spoke to doctor or pharmacist, discussed with family/friends) were assessed at M3. PPPP costs ($US 2013) included staff time, PV, actor, and site fees. RESULTS: Of 276 attending PPPP, 190 consented and were included in the ITT sample, which was largely black (80.5%) and female (76.3%) and had a mean age of 74.4 years. Knowledge improved by 46.8% (BL vs PT), with significant gains in all domains. At M3, knowledge improved by 54.2% vs BL, indicating sustained gains; 37.2% of previously unvaccinated participants reported receiving PV by M3. Program cost was $119 per attendee. CONCLUSION: PPPP significantly improved PD and PV knowledge. It could be delivered more efficiently by holding larger events on fewer dates, staffing with volunteers where appropriate, and utilizing a local pharmacy to manage the vaccine supply.

Tenofovir Alafenamide.

OBJECTIVE: To review the pharmacology, efficacy, safety, and place in therapy for tenofovir alafenamide (TAF). DATA SOURCES: A search using PubMed was conducted (2004 to May 2016) using the following keywords: tenofovir alafenamide, TAF, and GS-7340. Articles were evaluated for content, and bibliographies were reviewed. Data available exclusively as abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion. STUDY SELECTION AND DATA EXTRACTION: Studies included were in vitro investigations; phase I, II, and III clinical trials; and pharmacokinetic and pharmacodynamic evaluations. DATA SYNTHESIS: Similar to tenofovir disoproxil fumarate (TDF), TAF is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. As a result, TAF is expected to have efficacy similar to that of TDF while reducing tenofovir-associated nephrotoxicity and bone mineral density losses. Clinical trials evaluating the safety and efficacy of TAF-containing antiretroviral regimens have confirmed these expectations, consistently demonstrating similar virological suppression compared with TDF-containing regimens as well as significant improvements in markers of kidney function and bone health. Three combination products containing TAF were approved by the United States Food and Drug Administration for the management of HIV-1 infection. The first of these was a single tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF which is now a recommended regimen in clinical practice guidelines for initial treatment in antiretroviral-naïve patients. CONCLUSIONS: TAF is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection that has efficacy similar to that of TDF and improved safety compared with TDF.

Cobicistat: Review of a Pharmacokinetic Enhancer for HIV Infection.

PURPOSE: This article reviews the clinical pharmacology, pharmacodynamic and pharmacokinetic (PK) properties, clinical efficacy and tolerability, drug interactions, and dosing and administration of cobicistat. METHODS: Searches of MEDLINE and International Pharmaceutical Abstracts from 1964 to February 2015 were conducted using the search terms cobicistat and GS-9350. Relevant information was extracted from the identified clinical trials and review articles. Abstracts from the Conference on Retroviruses and Opportunistic Infections (2014-2015) and the Interscience Conference on Antimicrobial Agents and Chemotherapy (2013-2014) were also searched. FINDINGS: Cobicistat is a PK enhancer lacking antiviral activity that, via selective cytochrome P-450 (CYP) 3A inhibition, inhibits the metabolism of certain antiretroviral medications and is used for prolonging their effect. Cobicistat has been studied as a booster of elvitegravir, a second-generation integrase inhibitor, and of the protease inhibitors atazanavir and darunavir. Data on its clinical efficacy and tolerability have been presented in 2 Phase II trials and in 9 Phase III trials, which reported durable efficacy in terms of achievement of sustained suppression of HIV-1 RNA levels to <50 copies/mL for at least 48 weeks. Cobicistat was generally well-tolerated in these studies. Cobicistat may increase serum creatinine levels via the inhibition of proximal renal tubular cell transporters and thus reduce estimated glomerular filtration rate, although it does not appear to affect actual glomerular filtration rate. Given the potent CYP3A inhibition by cobicistat, its coadministration with drugs metabolized by CYP3A may result in increased plasma concentrations of such agents. Moreover, as cobicistat is metabolized predominantly by CYP3A, plasma concentrations may increase or decrease on coadministration with CYP3A inhibitors or inducers, respectively. IMPLICATIONS: With potent durability through 48 weeks, a tolerability profile comparable to other first- and second-line antiretroviral therapies, and a convenient dosing schedule with low daily pill burden in fixed-dose combination tablets, cobicistat is a potential addition to the management of HIV infection as a PK enhancer. However, the effects of cobicistat on serum creatinine and its considerable drug-interaction potential may warrant additional monitoring.

Once-Daily, Single-Tablet Regimens For the Treatment of HIV-1 Infection.

Once-daily, single-tablet regimens have become integral to the management of human immunodeficiency virus type 1 infection, partly because they may improve adherence due to a lower pill burden. This article reviews the single-tablet options.

Saliva diagnostics: utilizing oral fluids to determine health status.

Imagine a time where your health status could be available to you without the pain, discomfort and inconvenience of a physical examination. Distant vision of an inconceivable future or impending reality with potentially immeasurable impact? Recent advancements in the field of molecular diagnostics indicate this is not only possible, but closer than we think. Novel discoveries and substantial advancements have revealed that saliva may contain real-time information describing our overall physiological condition. Researchers are now reporting that, like blood and tissue biopsies, oral fluids could be a source of biochemical data capable of detecting certain diseases. What is even more intriguing is that this phenomenon not only applies to local disorders like oral cancer and Sjögren's syndrome, but distant pathologies like autoimmune, cardiovascular and metabolic diseases as well as viral/bacterial infections and even some cancers. These revelations have provided a foundation for the burgeoning field of salivary diagnostics and hence spurred the onset of investigations poised at deciphering the salivary milieu. This paper overviews salivary diagnostics from biomarker development to the multitude of techniques utilized in identifying saliva-based molecular indicators of disease. In doing so, we present oral fluids as an easily accessible noninvasive alternative to traditional diagnostic avenues and not just an essential component of the digestive process. Determining saliva as a credible means of evaluating health status represents a considerable leap forward in health care, one that could lead to enormous translational advantages and significant clinical opportunities.

Mycobacterium avium complex (MAC) Immune Reconstitution Syndrome (IRIS) With Reduced Susceptibility to Ethambutol in an HIV-Infected Patient.

OBJECTIVE: To describe a case of Mycobacterium avium complex (MAC) lymphadenitis complicated by immune reconstitution syndrome (IRIS) and reduced susceptibility to ethambutol. CASE SUMMARY: A 24-year-old man was diagnosed in October 2012 with advanced HIV infection upon hospitalization for multiple opportunistic infections (OIs). Within 5 months of starting antiretroviral therapy, the patient developed significant cervical lymphadenopathy concerning for MAC/IRIS. Acid-fast bacilli were detected in the primary lymph node biopsy smear, and culture results confirmed the presence of MAC. Susceptibility testing revealed an organism susceptible to azithromycin, with an elevated minimum inhibitory concentration (MIC) to ethambutol (8 µg/mL). Currently, there is no interpretation for an ethambutol MIC of 8 µg/mL for MAC. A review of the primary literature revealed the possibility of decreased ethambutol susceptibility when the MIC is above 1 µg/mL, and therefore, therapy was replaced by rifabutin in combination with azithromycin. DISCUSSION: Current guidelines recommend a 2-drug regimen for the treatment of MAC, specifically a macrolide plus ethambutol. Guidelines also emphasize MAC susceptibility testing for macrolides only. Susceptibility results from this patient's biopsy prompted an evaluation of the effectiveness of his antimycobacterial regimen. CONCLUSIONS: Reduced ethambutol susceptibility in this patient triggered a search of the primary literature that resulted in the decision to replace ethambutol with rifabutin. Additional clinical trials are needed to define susceptibility breakpoints for ethambutol and other antimycobacterial agents used for MAC infection treatment and to direct clinical decisions when elevated MICs to primary agents are identified.

Dolutegravir: a new integrase strand transfer inhibitor for the treatment of HIV.

The first two integrase strand transfer inhibitors (INSTIs) approved for treatment of patients infected with human immunodeficiency virus (HIV) were raltegravir and elvitegravir. Both raltegravir and elvitegravir are now guideline-preferred agents as part of an antiretroviral regimen for treatment-naive patients. However, raltegravir is dosed twice/day. Elvitegravir is available in a single-tablet regimen and dosed once/day because it is administered with the pharmacokinetic booster cobicistat, a potent CYP3A4 inhibitor that can lead to clinically significant drug-drug interactions. In addition, raltegravir and elvitegravir have a low genetic barrier to resistance and are associated with cross-resistance. Dolutegravir is a new-generation INSTI administered once/day without a pharmacokinetic booster and can be coformulated in a single-tablet regimen. Phase III studies have demonstrated the efficacy and safety of dolutegravir for treatment-naive and treatment-experienced patients. Compared with other INSTIs, dolutegravir has a higher genetic barrier to resistance. Dolutegravir was approved by the U.S. Food and Drug Administration in August 2013 and joins raltegravir and elvitegravir as guideline-preferred agents for the management for HIV-infected treatment-naive patients.

Salivary biomarkers: toward future clinical and diagnostic utilities.

The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Here we discuss saliva and its significance as a source of indicators for local, systemic, and infectious disorders. We highlight contemporary innovations and explore recent discoveries that deem saliva a mediator of the body's physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis.