Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.

The Role of Antisense Therapies Targeting Lipoprotein(a).

ABSTRACT: Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.

Outpatient management of chronic warfarin therapy at a pharmacist-run anticoagulation clinic during the COVID-19 pandemic.

As a result of infection control regulations during the coronavirus disease 2019 (COVID-19) pandemic, anticoagulation clinics have been required to adjust their practices in order to continue providing safe and effective services for their patients. In accordance with a guidance document issued by the Anticoagulation Forum, The Brooklyn Hospital Center (TBHC) anticoagulation clinic in Brooklyn, New York implemented measures including telemedicine follow-ups instead of in-person clinic visits, extending the interval of INR testing, and reviewing eligible candidates for transition from warfarin to direct oral anticoagulants. This study describes the outcomes of one hospital-based clinic location in the 3 months before and after COVID-19 became a significant concern in the New York City area. The primary outcome of time-in-therapeutic range (TTR) for patients receiving warfarin was 60.6 % and 65.8 % in the pre-COVID and post-COVID groups, respectively (p = 0.21). For secondary outcomes, there was no difference in percent of therapeutic INRs (51.5 % pre-COVID v. 44.8 % post-COVID, p = 0.75) or percent of INRs ≥ 4.5 (2.3 % pre-COVID v. 4 % post-COVID, p = 0.27). Based on the data reported in this study, the short-term changes implemented at TBHC's anticoagulation clinic did not appear to cause reductions in safety and efficacy of chronic warfarin therapy management.

Evaluation of Teaching Activities Completed by PGY2 Pharmacy Residents at Colleges of Pharmacy.

Introduction: Evaluating PGY2 pharmacy residency programs and their academic opportunities is crucial for developing future clinician-educators and advancing pharmacy education. There is a lack of newer data available on residency programs' teaching activities and older studies are limited by timely survey instruments and low response rates. The objective of this project was to describe teaching responsibilities among PGY2 pharmacy residents nationwide using a short, electronic survey. Methods: A survey consisting of ten multiple-choice questions was emailed to residency program directors to assess the teaching and precepting responsibilities of PGY2 and PGY1/PGY2 combined pharmacy residents across the country. The survey was converted to an online form using QualtricsXM and had an estimated completion time of 2 min. Data was reviewed and analyzed using descriptive statistics. Results: A total of 292 out of 594 PGY2 or PGY1/PGY2 combined pharmacy residency program directors responded to the survey (49% response rate), with the majority of programs being ASHP-accredited. Only 13% of PGY2 residency programs surveyed did not have their residents complete a didactic lecture at a college of the pharmacy and 50% of programs have their residents facilitate labs or recitations at colleges of pharmacy. Sixty-eight percent of programs have their residents serve as the primary preceptor for experiential rotations. Conclusion: The majority of PGY2 pharmacy residency programs include teaching opportunities. Continuous efforts are needed to increase teaching opportunities for PGY2 residents to help fill vacant academic positions with qualified academicians.

Evaluation of the Use of Social Media and Virtual Meeting Platforms in the Pursuit of Pharmacy Residency Training.

Introduction: The American Society of Health-Systems Pharmacists (ASHP) and American College of Clinical Pharmacy (ACCP) Residency Directories are two of the more traditional resources available to pharmacy students and residents looking for post-graduate programs. More recently, social media platforms have grown as an innovative means of resident recruitment and program marketing. Objective: The objective of this study was to evaluate the use of social media by both PGY1 and PGY2 candidates in their pursuit of post-graduate training through the disbursement of a survey. Methods: A survey consisting of 14 questions ranging from multiple-choice questions to free-text options was emailed out to the Office of Experiential Education from 141 ACCP-accredited pharmacy schools and 1341 ASHP-accredited PGY1 Pharmacy Residency Program Directors, requesting them to forward the email to their students or residents. Results: There were a total of 714 respondents to the survey. A majority of surveyors were in the process of completing a PGY1 residency training program (70.6%). The most common platform used to research pharmacy residency programs was the ASHP directory (97.3%). A majority of respondents did not use social media to research residency programs (66.7%). Out of the ones who did use social media, Instagram was the most common platform used and provided the greatest insight into the residency program. About 60% of respondents preferred Zoom as the virtual meeting platform during interviews. Conclusion: Although social media may not be the main source of information candidates are using, residency program accounts can provide residency programs with a free additional tool for recruitment.

The Impact of Escape Room Gamification Using a Teleconferencing Platform on Pharmacy Student Learning.

Objective: The purpose of this study is to design and implement a virtual escape room game using the Zoom video conferencing platform to enhance third professional doctor of pharmacy students' knowledge of self-management of sexual health and pregnancy prevention and to assess student's perception of the activity. Methods: Students were divided into five pre-assigned breakout rooms of five to six students each using the Zoom video conferencing platform, following the conclusion of the self-care sexual health and pregnancy prevention lecture. Once in the breakout room, students worked as a group to complete seven activities to gain access to a code needed to "escape the room." At the completion of the activity, students were asked to fill out a perceptions survey. Results: Twenty-six students participated in the virtual escape room activity, with all students completing the activity within the allotted time. Overall, students expressed positive attitudes toward the escape room activity, reporting it helped them check their knowledge of the subject, remain motivated, and connect with their classmates. Conclusions: Overall, the virtual escape room had a positive impact on student learning and application of subject material.

Evaluation of rates of virologic suppression in HIV-positive patients with varying numbers of comorbidities.

PURPOSE: To evaluate the impact of the number of comorbidities on virologic suppression in HIV-positive patients. METHODS: This study included patients 18 years or older who were on antiretroviral therapy (ART) with at least 2 visits to an HIV primary care clinic in the past year. The primary outcome was the percentage of patients with an undetectable viral load (a blood HIV RNA level of <20 copies/mL) among groups of patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, respectively. The secondary outcome was the percentage of patients with undetectable viral loads per each comorbidity, as listed above. The study was reviewed by an institutional review board and approved as exempt from full review. RESULTS: Among the 1,144 patients (median age of 52 years, 43% female, 74% Black) included in the study, 80% had an undetectable viral load, and the mean CD4 count was 638 cells/mm3. The majority of patients (48%) had 1 or 2 comorbidities, with only 2 patients having 5 comorbidities. For patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, the percentages of patients with undetectable HIV viral loads were 76%, 81.7%, 87.9%, and 100%, respectively (P = 0.0009 in χ 2 test for trend). When looking at individual comorbidities, corresponding viral suppression rates were as follows: chronic kidney disease, 88.6%; hypertension, 85.8%; type 2 diabetes, 85.7%; clinical atherosclerotic cardiovascular disease, 83.1%; substance abuse, 76%; and psychiatric disorders, 75.2%. CONCLUSION: Improved viral suppression was seen among HIV-positive patients with an increased number of comorbidities. Patients with psychiatric disorders had the lowest viral suppression rates amongst all of the comorbidity subgroups.

Use of Lidocaine Cream for Pain Management During Immunizations of Infants at an Urban Health Clinic.

BACKGROUND: Immunizations are a common source of pain and anxiety within the pediatric population. Implementation of lidocaine 4% cream, which has a short onset of action, as a standard of care for immunization practices may be feasible. OBJECTIVE: The objective of this study was to assess the efficacy of lidocaine 4% cream as pain management during immunizations and to evaluate satisfaction of caregivers and nursing staff. METHODS: This study was a prospective, randomized, placebo-controlled trial in an urban clinic, which included patients who were ≤ 14 months old accompanied by a caregiver who witnessed the patient receiving an immunization within the previous 7 months. Patients were randomized to receive either lidocaine 4% cream or placebo cream prior to vaccination. Time to cry and duration of cry were recorded. Caregivers completed surveys evaluating attitudes toward pain associated with immunizations as well as their satisfaction with the immunization process through Likert Scale ratings. Nurses completed a questionnaire assessing efficacy and feasibility of lidocaine 4% cream for pain management. RESULTS: A total of 44 patients were included in the analysis in order to achieve 80% power with a p-value < 0.05. Mean duration of cry in patients receiving lidocaine 4% cream was 48.6 seconds in comparison to 65.9 seconds in patients receiving placebo (95%CI, -33.97 seconds to -0.48 seconds; p < 0.05). CONCLUSIONS: Lidocaine 4% cream decreased total duration of cry following vaccinations in comparison to placebo with both caregivers and nurses willing to utilize lidocaine 4% cream in a clinic setting if available.

Evaluation of virologic suppression rates during the COVID-19 pandemic with outpatient interdisciplinary HIV care.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has presented social distancing challenges leading healthcare systems to adapt and utilize telemedicine platforms more than ever before. Reducing patient exposure to COVID-19 became a primary concern, especially for populations at an increased risk for severe illness, such as human immunodeficiency virus (HIV) positive patients. Objectives: The primary objective of this study was to measure the impact of pharmacy services including telehealth through the percentage of virologically suppressed patients (HIV ribonucleic acid [RNA] < 200 copies/mL) during the pre-COVID and post-COVID time periods. Secondary objectives included the percentage of patients with undetectable viral loads (HIV RNA < 20 copies/mL), percentage of patients with cluster of differentiation 4 (CD4) cell counts greater than 200 cells/mm3, and changes in CD4 cell counts and percentages pre-COVID and post-COVID. Methods: This was a retrospective chart review at a single center HIV primary care clinic in Brooklyn, NY evaluating electronic medical records (EMRs) of 211 HIV-positive patients. Pre-COVID was defined as 1 year prior to March 13, 2020, and post-COVID was defined as March 13 to July 20, 2020. Results: Viral load suppression rates for pre and post-COVID were 88.6% and 85.3%, respectively (P = .28). Undetectable viral load rates for pre and post-COVID were approximately 81.5% and 74.4% (P = .096). Mean CD4 cell counts and percentages were 617 cells/mm3 and 29% for pre-COVID, and 460 cells/mm3 and 22% for post-COVID. CD4 cell counts greater than 200 cells/mm3 pre-COVID and post-COVID was 92.6% and 78.3%, respectively (P = .001). Conclusion: Utilization of pharmacy services including telehealth, may allow clinical pharmacists to collaboratively provide remote services without jeopardizing patient outcomes. Larger studies are needed to confirm these findings, and display the long-term impact and satisfaction of these services.

Serological response with Heplisav-B® in prior Hepatitis B vaccine non-responders living with HIV.

BACKGROUND: As people living with HIV (PLWH) are at risk for contracting Hepatitis B Virus (HBV), they should be screened for HBV and vaccinated if not immune. Seroconversion rates in PLWH receiving traditional recombinant HBV vaccines (Engerix-B® and Recombivax-HB®) have historically been low with at most 70% achieving immunity. In 2017, a recombinant, adjuvanted HBV vaccine (Heplisav-B®) was approved for use in HIV-negative patients. Heplisav-B® has shown superior seroprotection in this population compared to Engerix-B® and Recombivax-HB®, as well as interim analysis showing higher seropositivity rates in patients undergoing dialysis. However, its efficacy in PLWH is currently unknown. This study evaluates the rate of seroconversion following Heplisav-B® administration in PLWH with previous HBV vaccination failure. METHODS: Retrospective, cross-sectional study at The Brooklyn Hospital Center's HIV primary care clinic in Brooklyn, NY. HIV-positive adults who received at least two doses of Heplisav-B® and had previously failed to seroconvert after vaccination with Engerix-B® or Recombivax-HB® were included. The primary outcome is the percentage of PLWH who became seropositive following Heplisav-B®. RESULTS: A total of 67 patients met the inclusion criteria. Twenty-five (37.3%) PLWH had failed at least 2 courses of recombinant vaccines. Fifty-eight (86.6%) PLWH became seropositive (Anti-HBs > 10 mIU/mL) at least two months after completing Heplisav-B®. For the 9 (13.4%) patients that did not develop immunity, 3 (33%) had a detectable HIV RNA and 3 (33%) had a CD4 count < 200 cells/uL3. CONCLUSIONS: Heplisav-B® was highly effective in achieving immunity to HBV in PLWH who failed non-adjuvanted recombinant vaccines.

Using PBPK Modeling to Predict Drug Exposure and Support Dosage Adjustments in Patients With Renal Impairment: An Example with Lamivudine.

BACKGROUND: Lamivudine is a nucleoside reverse transcriptase inhibitor used to treat HIV and hepatitis B. It is primarily cleared by the kidney with renal secretion mediated by OCT2 and MATE. OBJECTIVE: To use PBPK modeling to assess the impact of renal impairment on lamivudine pharmacokinetics using the Simcyp® Simulator. METHODS: The model incorporated the Simcyp® Mechanistic Kidney Model option to predict renal disposition. The model was initially verified using the Simcyp® Healthy Volunteer population. Two discrete patient populations were then created for moderate (GFR 10-40 mL/min) and severe (GFR < 10 mL/min) renal failure (RF), and model simulations were compared to published data. The developed model was then utilized in a clinical study evaluating the clinical experience and plasma exposure of lamivudine when administered at higher than recommended doses to HIV-infected patients with varying degrees of renal impairment. RESULTS: Predicted systemic exposure metrics (Cmax, AUC) compared favorably to published clinical data for each population, with the following fold errors (FE, ratio of predicted and observed data) for Cmax/AUC: Healthy Volunteers 1.04/1.04, Moderate RF 1.03/0.78, Severe RF 0.89/0.79. The model captured lamivudine plasma concentrations measured pre- and post-dose (0.5-1.5hr) in study participants (n = 34). Model simulations demonstrated comparable systemic profiles across patient cohorts, supporting the proposed dosage adjustment scheme. CONCLUSION: This study illustrates how PBPK modeling can help verify dosing guidelines for patients with varying levels of renal impairment. This approach may also be useful for predicting potential changes in exposure during renal insufficiency for compounds undergoing clinical development.

Safety and Efficacy of Weight-Loss Pharmacotherapy in Persons Living with HIV: A Review of the Literature and Potential Drug-Drug Interactions with Antiretroviral Therapy.

The prevalence of obesity among persons living with human immunodeficiency virus (HIV) has increased significantly and may be linked to the use of antiretroviral therapy. Although weight-loss medications approved by the U.S. Food and Drug Administration are recommended as an adjunct to diet and exercise to treat obesity in the general population, little is known about the safety and efficacy of these drugs specifically in persons living with HIV. We review the available evidence regarding the effective use of weight-loss pharmacotherapy in persons living with HIV and its potential to interact with antiretroviral therapy. Persons living with HIV are frequently not reported or included in clinical trials for weight-loss medications; however, treatment efficacy is likely similar to the general population. Several important reported or theoretical drug-drug interactions exist between antiobesity pharmacotherapy and antiretroviral therapy. Orlistat is a weight-loss drug available in the United States without a prescription and was linked to HIV viral rebound in several case reports. Clinicians should be aware of the potential for loss of HIV viremia control when certain weight-loss pharmacotherapies are used in combination with antiretrovirals.

Real-World Experience With Higher-Than-Recommended Doses of Lamivudine in Patients With Varying Degrees of Renal Impairment.

BACKGROUND: Although nucleoside reverse transcriptase inhibitors have been associated with lactic acidosis, lamivudine (3TC) has not been reported to have an increased risk with elevated concentrations. Therefore, some recommend that the lowest tablet strength of 3TC be considered in patients with kidney disease to avoid the inconvenience of liquid formations. Our institution avoids dose-adjusting 3TC until creatinine clearance (CrCl) <30 mL/min and uses 100-150-mg tablets daily in hemodialysis. The aim of this study was to describe the use of higher-than-recommended doses of 3TC in a real-world setting. METHODS: Blood samples were collected before and 0.5-1.5 hours after 3TC administration in HIV+ adults. Predose (Cmin) and postdose (Cmax) samples were measured by high-performance liquid chromatography. Physiologically based pharmacokinetic modeling was utilized to simulate areas under the curve (AUCs) and profiles by CrCl. Lactic acid levels and patient-reported adverse events were obtained to monitor for safety, and viral suppression was assessed for efficacy. RESULTS: Thirty-four patients with varying degrees of renal function were enrolled. Observed 3TC Cmax values were comparable among CrCl cohorts. Simulated 3TC AUC values in patients with CrCl 30-49, 15-29, and 0-15 mL/min were consistent with historical data, and fold-errors were between 0.5 and 2.0. All lactic acid levels were within normal limits, and no adverse effects were reported. CONCLUSIONS: This study is the first to describe the use of higher-than-recommended doses of 3TC in a real-world setting. 3TC was well tolerated across all levels of renal function. These results can guide providers in their selection of higher 3TC dosing in select patients with renal dysfunction to maximize adherence.

Prescriber Attitudes Toward Implementation of Pharmacogenomic Testing in a Family Medicine Residency Program.

INTRODUCTION: Few qualitative studies have explored the attitude of prescribers towards the implementation of pharmacogenomic testing in the family medicine (FM) setting, and none among FM residents. The purpose of this study was to describe the level of engagement and interest in the implementation of pharmacogenomic education and testing in an FM clinic within a residency program. METHODS: A qualitative study utilizing semistructured interviews was conducted among prescribers within the FM clinic at The Brooklyn Hospital Center (TBHC). Voluntary prescribers included FM residents and attendings. No prescribers were excluded. Prior to the interview, informational sheets about pharmacogenomics were provided to standardize participant knowledge base. The research team created an interview guide of specific open-ended questions. Interviews were audio recorded and transcribed until a point of saturation was achieved. Transcripts of interviews served as data for analysis. Coding and analysis were performed to develop a hypothesis. No formal statistical analysis was required. RESULTS: Of the total 28 providers eligible for participation, 15 were recruited and interviewed (53% response rate). Based on analysis of interview data, four key conceptual concerns emerged regarding benefits and risks of testing, feasibility, accessibility, and modification of FM residency training curricula. CONCLUSION: Positive attitudes and perceptions provide support for pharmacogenomic education and testing to be incorporated into FM residency curricula. Addressing practical barriers, such as curricular education and training, will allow for expansion of such initiatives in the future.