Elizabeth M. Sherman

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.

ASHP Guidelines on Pharmacist Involvement in HIV Care

The epidemic of human immunodeficiency virus (HIV) infection in the United States has changed dramatically since its initial recognition in 1981.[1][1] Early in the epidemic, the incidence of HIV reached over 130,000 new cases per year, and death as a result of acquired immunodeficiency syndrome (

Clinical infectious diseases pharmacists in the United States: a problem of both supply and demand

TO THE EDITOR—The importance of antimicrobial stewardship (AS) to the future of healthcare is emphasized by recent statements of the US government calling for widespread implementation of robust AS programs, which applies to >5700 US hospitals [1]. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance AS identify a clinical pharmacist with infectious diseases (ID) training as 1 of 2 core AS team members [2]. The Society of Infectious Diseases Pharmacists (SIDP) and Infectious Diseases Practice Research Network of the American College of Clinical Pharmacy (ACCP) recommend that future pharmacists seeking a clinical ID position complete a postgraduate year 1 (PGY-1) pharmacy practice residency and postgraduate year 2 (PGY-2) ID specialty residency [3]. Today, concern exists over the shortages of adequately trained ID pharmacists [4, 5], and as such, the future supply of clinical ID pharmacists is dependent on the availability of postgraduate ID training opportunities. The purpose of this correspondence is to objectively describe the current state of (1) postgraduate training opportunities for pharmacists looking to specialize in ID and (2) demand for clinical ID pharmacists. To quantify and characterize postgraduate training opportunities, we accessed pharmacy residency and fellowship directories of SIDP, American Society of Health-System Pharmacists (ASHP), and ACCP. Site information was crossreferenced to account for duplication, and available data points were collected for analysis. To assess the demand for clinical ID pharmacists, we utilized Web-based searches (eg, www.monster. com, www.usajobs.gov) and accessed employment postings provided by relevant pharmacy organizations (eg, ASHP, SIDP). These were compiled using Microsoft Excel software and evaluated individually to prevent duplication. We performed this snapshot assessment in October 2014, identifying 89 postgraduate ID training programs and 32 clinical ID pharmacist employment listings. Collected data are presented in Table 1. For training programs, none focused specifically on AS, although by nature AS concepts are incorporated into training and accreditation standards for PGY-2 ID residencies mentions AS briefly [7]. For employment, 23 (72%) mentioned AS within the job description and 29 (91%) were inpatient positions. In addition to the 32 clinical ID pharmacist positions, 5 academic and 10 industrybased (eg, medical science liaison) ID pharmacist jobs were found. If AS programs are destined to become part of the healthcare landscape and clinical ID pharmacists are essential for such a transition, the data presented here represent cause for substantial concern. Quantitatively and geographically, current opportunities for training and employment are considerably inadequate to fulfill the anticipated future needs for thousands of US institutions. Indeed, alternative educational programs such as certificate programs [8, 9] may assist in filling some existing gaps, but are limited in their scope. As healthcare continues to evolve and the role of AS grows, early recognition of existing barriers by stakeholders is essential to future success. The impact of the current clinical ID pharmacist supply and demand deficiencies within the United States noted here requires consideration during this AS program implementation and expansion period.

Heat-stable ritonavir tablets: a new formulation of a pharmacokinetic enhancer for HIV

Importance of the field: HIV is a worldwide epidemic that can be managed by combination antiretroviral therapy. Effective regimens commonly include the use of a ritonavir-boosted protease inhibitor (PI). In February 2010, the FDA approved heat-stable ritonavir tablets for management of HIV; these do not require refrigeration and may improve patient access. Areas covered in this review: The goal of this article is to review the ritonavir 100 mg heat-stable tablet formulation for the treatment of HIV, focusing on recent pharmacokinetic studies, safety and tolerability data, administration, and storage. What the reader will gain: With recent FDA approval, it is important that clinicians and pharmacists are knowledgeable about the differences between heat-stable ritonavir tablets and the previous soft-gel-capsule (SGC) formulation. Take home message: Heat-stable ritonavir tablets are not bioequivalent to previous SGC and differ in regards to storage requirements. Despite this, ritonavir tablets appear to be well tolerated and may provide additional options for selected patients with HIV.

Pharmacist Testers in Multidisciplinary Health care Team Expand HIV Point-of-Care Testing Program

Knowledge of HIV serostatus is the first step to accessing treatment, reducing transmission, and mitigating public health challenges. We describe the expansion of an HIV point-of-care testing (POCT) program within a health care system utilizing pharmacists as testers. The testing program’s expansion is detailed and its impact assessed. The POCT program was evaluated by comparing the number of traditional HIV venipuncture tests to the number of POCTs performed across the health system as well as comparing the number of POCTs performed by clinical pharmacists to the number of tests at other POCT locations. Although pharmacists’ contributions to HIV prevention are well documented, pharmacists’ involvement in HIV testing initiatives is still nascent. Our POCT program demonstrates an effective HIV testing initiative driven by pharmacists and other health care providers.

An Elective Course on Antimicrobial Stewardship

Objective. To implement an antimicrobial stewardship (AS) elective course for second-year and third-year pharmacy students and to assess its impact on students’ perceptions regarding the application of AS principles. Design. A 2-credit elective course focusing on principles of AS incorporated prelecture didactic recordings with primary literature and guideline-based reading assignments, in-class active-learning group work and student-led presentations, and student-generated examination items. Assessment. Perceptions were assessed by precourse and postcourse survey items. Graded course assessments included completion of preclass assignments (readings, prerecorded lecture and writing assessment items), in-class active participation and group presentations, a midpoint examination, and a final examination. Conclusion. An AS-themed elective course in a doctor of pharmacy curriculum incorporating preclass, self-directed learning and in-class group-based active-learning strategies positively impacted students’ perceived understanding of AS strategies.

Pharmacist engagement within a hepatitis C ambulatory care clinic in the era of a treatment revolution

OBJECTIVES To describe an innovative hepatitis C virus (HCV) care program and treatment outcomes resulting from pharmacist services. SETTING Adult ambulatory care HCV clinic within the Miami Veteran Affairs Healthcare System. PRACTICE DESCRIPTION Pharmacists with limited prescriptive authority are integrated into a medical hepatology care team. PRACTICE INNOVATION Pharmacists screen patients with HCV infection for treatment eligibility, counsel patients upon treatment initiation, assess ongoing treatment success and toxicity through patient appointments, telephone calls, and the ordering of pertinent laboratory data, and provide oversight of all patients on HCV therapies. Treatment outcomes are reported to the institutional Antimicrobial Stewardship Program. EVALUATION Data produced from a continuous quality assurance initiative were utilized. Descriptive statistics were used to present data. RESULTS From January 2014 through September 2015 there were 1619 pharmacist encounters for 532 unique patients and 597 screenings (including 578 approvals) were completed by a pharmacist. During this time 555 patients were initiated on at least 1 HCV treatment course, with 565 total treatment courses initiated. As new agents became available for use, fluctuation in regimen selection was seen. The most commonly prescribed medications were sofosbuvir (46%), ledipasvir/sofosbuvir (37%), and simeprevir (33%). Of the 565 HCV treatment courses initiated, 360 were completed, 29 were stopped early during treatment, and 176 were ongoing. Of the 360 completed courses, 249 had sustained virologic response at week 12 results available, of which 225 (90%) achieved treatment success and 24 (10%) relapsed. Of the 29 courses stopped early, 11 were due to poor medication adherence and 8 were due to adverse drug reaction. CONCLUSION Through a structured process employing a scope of practice, pharmacists can extend the capacity of medical hepatology providers and provide pharmacotherapy services to enhance care. Information provided here may serve beneficial to others looking to initiate or expand existing HCV pharmacist services.

Elvitegravir for the treatment of HIV

ABSTRACT Introduction: Current antiretrovirals (ARVs) have demonstrated the ability to prolong the life of an HIV infected individual via suppression of the virus and subsequent restoration of immune function. Despite significant advancement, there remains an opportunity for improvement. One ARV that attempts to fill global HIV therapeutic needs by balancing convenience, safety, and efficacy is elvitegravir (EVG). Areas covered: Using MEDLINE/PubMed, a literature search was conducted for published articles on the safety and efficacy of EVG in the treatment of HIV infection. Expert opinion: EVG offers clinicians a convenient choice for HIV-positive patients that is safe and effective for both treatment-naïve and experienced patients, as well as an option for regimen simplification in virologically suppressed patients. EVG is conveniently co-formulated in fixed dose combination tablets to be taken once daily with food. EVG does not require dose adjustment for patients with severe renal impairment or mild to moderate liver disease. Importantly, EVG requires co-administration with a pharmacokinetic enhancer (i.e., ritonavir or cobicistat) in order to achieve therapeutic levels and facilitate once daily dosing. As a consequence, clinicians must carefully review concomitant medications and navigate potential drug-drug interactions mediated through potent inhibition of cytochrome P450 3A enzymes by ritonavir and cobicistat.

Strength in Amalgamation: Newer Combination Agents for HIV and Implications for Practice

Antiretroviral (ART) therapy for the treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single‐tablet regimens (STRs), including newer fixed‐dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug‐drug interactions. Newer STRs include dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) (Triumeq; Viiv Healthcare, Research Triangle Park, NC), rilpivirine (RPV)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Odefsey; Gilead, Foster City, CA), RPV/FTC/tenofovir disoproxil fumarate (TDF) (Complera; Gilead), elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF (Stribild; Gilead), and EVG/COBI/FTC/TAF (Genvoya; Gilead). Recently approved FDCs, such as atazanavir (ATV)/COBI (Evotaz; Bristol‐Myers Squibb, Princeton, NJ), darunavir (DRV)/COBI (Prezcobix; Janssen Products, Titusville NJ), and FTC/TAF (Descovy; Gilead), are also now available. The Department of Health and Human Services treatment guidelines for HIV recommend many of these integrase strand transfer inhibitor (INSTI) STRs as a preferred choice for initiation of treatment in both ART‐naive and ‐experienced patients because they offer comparably faster rates of virologic suppression, reduced rates of resistance development (especially with DTG), and overall better adherence than protease inhibitors or NNRTIs. Numerous phase 3 clinical trials support these recommendations including several switch or simplification clinical trials. Notably, the novel pharmacokinetic booster COBI, with its water soluble properties, has enabled the development and coformulation of a few of these STRs and FDCs. Also, a newer tenofovir salt formulation, TAF, has an advantageous pharmacokinetic profile, contributing to better overall renal and bone tolerability compared with TDF. Further simplification regimens comprising dual ART therapies are currently being explored. This review provides an overview of the clinical efficacy and safety data for these coformulated agents, highlighting the relative impact on comparative adverse events, assessing the potential for experiencing fewer drug‐drug interactions, and discussing the clinical implications regarding adherence to treatment.

Patient Perceptions of Text Messaging to Improve Antiretroviral Therapy Adherence: A Qualitative Study of Patients in a Ryan White Clinic:

Evidence on the use of short message service (SMS) to improve medication adherence in people living with HIV (PLHIV) is mounting, yet qualitative research on patient perceptions regarding SMS content and utility for HIV/AIDS remains nascent. To explore the experience of receiving medication reminders via SMS among PLHIV, 45 uninsured and underinsured PLHIV nested within the intervention arm of a larger study received daily, 1-way SMS adherence reminders. Qualitative data were collected by face-to-face, structured interview and were analyzed using conventional content analysis methods. Three main themes emerged from the data: (1) reminders helping with adherence, (2) concerns about delivery modes, and (3) the need for confidentiality. Study findings offer enhanced focus on an emerging strategy in patient-centered HIV care: Equipped with greater context on the experiences of PLHIV using SMS adherence reminders, health-care providers can offer more targeted support and thereby maximize the benefits of this popular and powerful technology.