Implementation of a Pharmacist-Led, Long-Acting, Injectable Cabotegravir/Rilpivirine Program for HIV-1 at Health System-Based Clinics in the New York Metropolitan Area.

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.

A system approach to improving guideline-directed therapy for cardio-renal-metabolic conditions: The "beyond diabetes" initiative.

Objective: Despite demonstrating improvements in cardiovascular disease, kidney disease, and survival outcomes, guideline-directed antihyperglycemic medications such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1-RA), are underutilized. Many obstacles constrain their use including lack of systematic provider and patient education, concern for medication side effects, and patient affordability. Methods: We designed a multimodality, systems-based approach to address these challenges with the goal of increasing medication utilization across the largest healthcare system in New York State. This multispecialty collaborative included provider and patient education, an electronic health record-enabled platform to identify eligible patients, and access to pharmacists for medication guidance and addressing insurance coverage barriers. Surveys were administered following grand rounds lectures and knowledge-based questionnaires were given before and after case-based sessions for housestaff, with results analyzed using a two-sided Student's t-test. Rates of first prescriptions of SGLT2i/GLP1-RA in combined and individual analyses were compared between the pre- and post-education periods (6 months prior to 3/31/2021 and 6 months post 8/19/2021), and the change in prescriptions per 100 eligible-visits was assessed using the incidence density approach. Results: Among grand rounds participants, 69.3% of respondents said they would make changes to their clinical practice. Knowledge increased by 14.7% (p-value <0.001) among housestaff following case-based sessions. An increase in SGLT2i/GLP1-RA prescribing was noted for eligible patients among internal medicine, cardiology, nephrology, and endocrinology providers, from 11.9 per 100 eligible visits in the pre-education period to 14.8 in the post-education period (absolute increase 2.9 [24.4%], incidence risk ratio 1.24 [95% CI 1.18-1.31]; p-value <0.001). Increases in prescribing rates were also seen among individual medical specialties. Conclusions: Our "Beyond Diabetes" initiative showed an improvement in provider knowledge-base and was associated with a modest, but statistically significant increase in the use of SGLT2i and GLP1-RA throughout our healthcare system.

Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences.

BACKGROUND: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients. OBJECTIVE: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity. PATIENTS AND METHODS: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months. RESULTS: We identified 482 patients with CLL [405 White (153 1L, 252 R/R), 37 Black (17 1L, 20 R/R), 40 other/unidentified]. At baseline, 58.5% of all patients (68.8% of Black patients) had hypertension. At a median follow-up of 28.2 months, 31.1% of patients overall discontinued ibrutinib, 16.2% due to adverse events (12.2% 1L, 18.8% R/R). Overall, 46.0% of patients experienced ≥ 1 dose hold (40.2% 1L, 49.8% R/R), and 28.8% of patients experienced ≥ 1 dose reduction (24.9% 1L, 31.4% R/R). Among Black patients, ibrutinib was discontinued in 24.3% of patients (17.6% 1L, 30.0% R/R), 8.1% due to disease progression and 5.4% due to adverse events; 40.5% of patients experienced ≥ 1 dose hold (35.3% 1L, 45.0% R/R), and 32.4% of patients experienced ≥ 1 dose reduction (23.5% 1L, 40.0% R/R). CONCLUSIONS: Toxicity and disease progression were the most common reasons for ibrutinib discontinuations in the overall population and among Black patients, respectively. Encouraging research participation of underrepresented patient groups will help clinicians better understand treatment outcomes.

Ibrutinib, a Bruton tyrosine kinase inhibitor, is an approved oral targeted therapy for the treatment of chronic lymphocytic leukemia (CLL). Patients treated with ibrutinib can experience side effects (referred to as adverse events) and may need to reduce the drug dose (referred to as dose reductions) or stop treatment (referred to as discontinuations) for a variety of reasons. A previous study showed that patients who were treated with ibrutinib experienced frequent dose reductions and discontinuations. This study described dose reductions and discontinuations in a larger patient population treated with ibrutinib and also described outcomes in Black patients. Patients with CLL treated with ibrutinib were identified from five medical centers and were followed for a minimum of 6 months. Patients experienced frequent dose reductions and discontinuations in routine clinical practice. The most common cause of discontinuations was adverse events in the overall patient population and disease progression in the Black patient population. Black patients treated with ibrutinib had similar rates of dose reductions and discontinuations as the overall patient population. Rates of dose reductions and discontinuations for patients with CLL treated with ibrutinib were higher in this real-world study than in clinical trials.

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.

A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine.

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists. To reduce the risk of medication-related errors, antiretroviral stewardship programs (ARVSPs) are needed to enhance patient safety. This call to action, endorsed by the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine, is modeled upon the success of antimicrobial stewardship programs now mandated by the Joint Commission. Herein, we propose definitions of ARVSPs, suggest resources for ARVSP leadership, and provide a summary of published, successful strategies for ARVSP that healthcare facilities may use to develop locally appropriate programs.

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.

The Pharmacist's Expanding Role in HIV Pre-Exposure Prophylaxis.

The efficacy of pre-exposure prophylaxis (PrEP) to prevent HIV has been firmly established; however, the success of PrEP largely depends on access to care as well as high levels of medication adherence. One of the key areas of focus for the National HIV/AIDS Strategy for 2020 in the United States calls for full access to comprehensive PrEP services where appropriate and desired, with support for medication adherence. Despite advances and advocacy for PrEP since approval for adults in 2012, large rates of prescribing disparity exist among gender and race/ethnicity. In 2016, only 3.7% of all PrEP users were women and only 11.2% were black. As one of the most widely accessible health care resources, pharmacists are well positioned to improve patient understanding, promote medication adherence, provide key risk reduction counseling, and enhance PrEP efficacy. Pharmacists' knowledge and accessibility in nearly every urban and rural community can be leveraged as part of a comprehensive HIV prevention strategy to expand access to care and improve population health. As trusted health care professionals, pharmacists develop a strong rapport with patients and may be the key to address current disparities in PrEP prescribing patterns as well as serve as an essential liaison between patients and other members of the multi-disciplinary care team. The purpose of this review is to summarize available data on pharmacist involvement in various models of care providing PrEP services and to identify opportunities to maximize and expand the role of the pharmacist to improve access to PrEP.

Concomitant Treatment of Hepatitis C Virus and Diffuse Large B-Cell Lymphoma with Direct-Acting Antivirals in HIV Coinfection: A Case Report.

This report describes a case of concomitant treatment of advanced diffuse large B-cell lymphoma with chemoimmunotherapy along with direct-acting antivirals for hepatitis C virus in a patient coinfected with HIV. The patient tolerated gemcitabine, dexamethasone, cisplatin, and rituximab and achieved sustained virologic response after treatment with ledipasvir/sofosbuvir.

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.

Statin Use With the ATP III Guidelines Compared to the 2013 ACC/AHA Guidelines in HIV Primary Care Patients.

BACKGROUND: The 2013 Cholesterol Guidelines include a new atherosclerotic cardiovascular disease (ASCVD) risk calculator that determines the 10-year risk of coronary heart disease and/or stroke. The applicability of this calculator and its predecessor, the Framingham risk score (FRS) in Adult Treatment Panel (ATP) III, has been limited in patients with HIV. The objective of this study was to compare the risk scores of ASCVD and FRS in the initiation of statin therapy in patients with HIV. METHODS: We conducted a retrospective chart review of patients with HIV on statin therapy from October 1, 2013, to April 1, 2014. Data collection included patient demographics, pertinent laboratory test results, and medication list. The primary end point evaluated the level of agreement between the guidelines. RESULTS: Of 155 patients who met the inclusion criteria, 116 were treated similarly with both guidelines. This showed a moderate level of agreement ( P < .001). Forty-eight of 86 patients requiring statins were placed on the correct intensity statin using the 2013 guidelines. Regardless of which guideline, a majority of patients required statin therapy. CONCLUSION: A moderate agreement was found between both guidelines in terms of statin use when applied to an HIV patient population. Based on the 2013 guidelines and taking into account drug interactions with antiretrovirals, 44.2% of the patients were treated with an incorrect statin intensity.

Reversibility of renal dysfunction after discontinuation of tenofovir.

OBJECTIVES: The association of tenofovir (TDF) with nephrotoxicity has been a controversial issue. Few studies are published regarding the reversibility of renal dysfunction once TDF is discontinued. Studies have yet to be conducted in an urban, non-white patient population, making this one of the largest studies observing a non-white cohort. The objective of this study was to determine whether the decline in creatinine clearance (CrCL) associated with TDF use is reversible once TDF is discontinued in a non-white patient population. METHODS: This single-center, retrospective, chart review was performed at an urban outpatient HIV clinic. Patients who had been switched from tenofovir to zidovudine or abacavir because of a decline in renal function were included. The primary endpoint was the percentage of patients who regained full, moderate, mild, or no recovery of CrCl. RESULTS: Sixty-two patients were included. The mean age was 50 years old, 82% were black, and 66% were males with a mean baseline CrCL of 76 ml/min. Mean difference in CrCL from baseline to 12 months post-TDF was shown to be -11.34 ml/min. After a 1-year follow up period, 37.5% of patients had a full recovery of their baseline CrCL. An additional 41% of patients achieved a moderate recovery (80%-99% of baseline CrCL) and 17.9% patients had a mild recovery (50%-79% of baseline CrCL). Two patients required dialysis. The percent of patients with an undetectable HIV RNA while on a TDF-containing regimen was 67.1% compared with 74.6% on alternative ART. CONCLUSION: Renal dysfunction caused by TDF was fully reversible in 37.5% of patients. Improvement to at least 50% of baseline was seen in 96.4% of patients. Viral suppression was not compromised when patient was switched from TDF to an alternative nucleoside reverse transcriptase inhibitor.

Real-World Sustained Virologic Response Rates of Sofosbuvir-Containing Regimens in Patients Coinfected With Hepatitis C and HIV.

BACKGROUND: Patients with hepatitis C virus (HCV) with or without human immunodeficiency virus (HIV) achieve high sustained virological response (SVR) rates on sofosbuvir (SOF)-containing regimens in clinical trials. Real world data on patients coinfected with HCV and HIV treated with SOF-based regimens are lacking. METHODS: This observational cohort study included HIV/HCV-coinfected adults with genotype 1 HCV who initiated treatment with a SOF-containing regimen between December 2013 and December 2014 (n = 89) at the Mount Sinai Hospital or the Brooklyn Hospital Center. The primary outcome was SVR at 12 weeks after the end of treatment. The secondary outcomes were risk factors for treatment failure, serious adverse events, and side effects. A post hoc per protocol analysis of SVR was performed on patients who completed treatment and follow-up. RESULTS: In an intention-to-treat analysis, SVR rates were 76% (31/41) for simeprevir (SMV)/SOF, 94% (16/17) for SMV/SOF/ribavirin (RBV), and 52% (16/31) for SOF/RBV. The SVR rates of SMV/SOF/RBV and SMV/SOF did not differ significantly in this small study (P = .15). However the SVR rate of SMV/SOF/RBV was higher than that of SOF/RBV (P < .01). In a per protocol analysis, SMV/SOF/RBV had a higher SVR rate than SOF/RBV: 100% (16/16) vs 57% (16/28) (P < .01). The most commonly reported adverse effects were rash, pruritus, fatigue, and insomnia. One patient who had decompensated cirrhosis prior to treatment initiation died after receiving SMV/SOF. CONCLUSIONS: SMV/SOF ± RBV is an effective option with minimal adverse effects for most HIV-positive patients with genotype 1 HCV. SMV should be used with caution in patients with decompensated cirrhosis.

Prevention of perinatal transmission of zidovudine- and nevirapine-resistant HIV.

PURPOSE: The use of a three-drug regimen for the prevention of perinatal transmission of zidovudine- and nevirapine-resistant HIV is described. SUMMARY: A 17-year-old Hispanic woman infected with HIV arrived at our clinic for the management of her first pregnancy. The patient was in her second trimester of her pregnancy, had not previously been treated with antiretroviral therapy, and was only taking daily prenatal vitamins at the time of her first clinic visit. Her HIV RNA viral load was 240 copies/mL, and the virus was resistant to both zidovudine and nevirapine. Nelfinavir (compounded suspension), lamivudine, and zidovudine were prescribed for the mother, though she was generally nonadherent to therapy. Nelfinavir, lamivudine, and zidovudine were initiated for the newborn within eight hours of delivery. Six months later, the patient returned to the clinic in the first trimester of her second pregnancy. At this visit, her HIV RNA viral load was 120 copies/mL. After the birth of her second child, the infant received the same regimen received by her firstborn: zidovudine 4 mg/kg orally twice daily for six weeks, lamivudine 2 mg/kg orally twice daily for two weeks, and nelfinavir 55 mg/kg orally twice daily for two weeks. At four months of age, each infant was found to be HIV-negative. CONCLUSION: A prophylactic regimen that included nelfinavir, lamivudine, and zidovudine was used to prevent perinatal transmission of HIV in two neonates. The regimen was well tolerated, and both infants were determined to be HIV-negative at four months of age.

Evaluating the Impact of a Pharmacist-Led Antiretroviral Stewardship Program on Reducing Drug Interactions in HIV-Infected Patients.

PURPOSE: To compare the number of antiretroviral-related clinically significant drug-drug interactions (CSDDIs) occurring in hospitalized patients that were intervened upon before and after Antiretroviral Stewardship Program (ARVSP) expansion and to classify the interventions made to prevent errors. METHODS: A retrospective chart review of adult patients treated with antiretroviral therapy (ART) and who were hospitalized from September 2012 to February 2013. A CSDDI was defined as requiring an alternative therapy, dose adjustment, or schedule modification. Findings were compared to a prior study. RESULTS: A total of 185 admissions were included and 76 CSDDIs were identified, 19 (25%) occurred after ART approval. The percentages of CSDDIs that occurred after ART approval and were intervened upon before and after ARVSP expansion were 43% and 95%, respectively (P<.001). An additional 80 other interventions were made by the ARVSP. CONCLUSION: An ARVSP is critical in the prevention of CSDDIs and errors to improve safety in HIV-infected patients.

Evaluating the Effects of an Interdisciplinary Practice Model with Pharmacist Collaboration on HIV Patient Co-Morbidities.

Treatment of HIV now occurs largely within the primary care setting, and the principal focus of most visits has become the management of chronic disease states. The clinical pharmacist's potential role in improving chronic disease outcomes for HIV patients is unknown. A retrospective cohort study was performed for HIV-positive patients also diagnosed with diabetes, hypertension, or hyperlipidemia. Characteristics and outcomes in 96 patients treated by an interdisciplinary team that included a clinical pharmacist (i.e., the intervention group) were compared to those in 50 patients treated by an individual healthcare provider (i.e., the control group). Primary outcomes were changes from baseline over 18 months of HbA1c, low density lipoprotein (LDL), and blood pressure, respectively. Secondary outcomes included number of drug-drug interactions, HIV viral load, CD4 count, percent change in smoking status, and percent of patients treated to cardiovascular guideline recommendations. The interdisciplinary team had a significant improvement in lipid management over the control group (LDL: -8.8 vs. +8.4 mg/dL; p=0.014), and the smoking cessation rate over the study period was doubled in the interdisciplinary group (20.4% vs. 11.8%). Among those with an indication for aspirin, a significantly higher percentage of patients were prescribed the medication in the interdisciplinary group compared to the control group (85.5% vs. 64.9%; p=0.014). An informal cost analysis estimated savings of more than $3000 per patient treated by the interdisciplinary team. Based on these results, pharmacist involvement in an HIV primary care clinic appears to lead to more appropriate management of chronic co-morbidities in a cost-effective manner.

Interdisciplinary HIV care--patient perceptions.

PURPOSE: The purpose of this paper is to gauge patients' service perceptions of an interdisciplinary human immunodeficiency virus (HIV) clinic, which uses infectious disease physicians, medical residents, clinical pharmacists, nurses, social workers and students in HIV primary-care delivery. DESIGN/METHODOLOGY/APPROACH: Adult patients coming to the HIV clinic for a return visit to the interdisciplinary team completed a questionnaire based on a previously validated HIV-specific patient satisfaction study (n = 104). Fourteen modified items assessing overall care-quality and ten original items assessing interdisciplinary services were included. FINDINGS: Respondents reported high satisfaction levels with the clinic's services. The mean score for the care-quality items was 3.79 (possible 4). The interdisciplinary care items mean score was 3.69 (possible 4). For non-physician disciplines, respondents indicated that nurses, pharmacists and social workers played important roles in their clinic care. RESEARCH LIMITATIONS/IMPLICATIONS: Bias associated with patient selection and survey methods limit the generalizability. The study has implications for measuring interdisciplinary care provided at HIV clinics. ORIGINALITY/VALUE: This HIV outpatient care interdisciplinary model is not widely in use. Results are important for those involved in HIV service development and improvement. Findings support integrating non-physician providers into routine outpatient HIV medical visits.

Sofosbuvir: a new oral once-daily agent for the treatment of hepatitis C virus infection.

Sofosbuvir: A new oral oncedaily agent for the treatment of hepatitis C virus infection.

Incidence of Antiretroviral Drug Interactions During Hospital Course: The Role of a Pharmacist-Led Antiretroviral Stewardship Program.

Background: Human immunodeficiency virus (HIV) providers are treating more comorbid conditions with additional pharmacologic agents, resulting in patients with HIV being disproportionately at risk for clinically significant drug-drug interactions (CSDDIs). There is a potential to overlook these interactions and ultimately place patients at risk for drug toxicity, resistance, and virologic failure. Objective: To assess the burden of CSDDIs among patients receiving antiretroviral therapy (ART) within 24 hours of admission and to evaluate the effect of a clinical pharmacist operating through an antiretroviral stewardship (ARVSP) program in identifying and correcting potential drug interactions. Methods: Adult HIV-positive patients receiving ART who were admitted to The Brooklyn Hospital Center from November 2010 through January 2012 were included in the analysis. Drug interactions were categorized according to time frame (ie, within 24 hours of admission vs after 24 hours of admission) and type (ie, contraindicated combinations, dosage modifications, and frequency alterations). The Liverpool HIV drug reference, Micromedex drug database, and the Department of Health and Human Services Guidelines were used as comprehensive tools for identification of antiretroviral drug errors. Results: Eighty-four CSDDIs were identified from 252 admissions among 158 patients receiving ART during the study period. Of the identified CSDDIs, 61 (73%) occurred within 24 hours of admission and 23 (27%) later in the hospital course. Forty-eight drug interactions (57%) represented contraindicated drug combinations. Protease inhibitor-based regimens were associated with the highest percentage of CSDDIs (98%). Of all CSDDIs, the most common interacting drug class was acid-suppressive therapy (63%). Clinical pharmacists identified and intervened in 80% of the CSDDIs that occurred on patient admission with all interventions accepted. Conclusions: CSDDIs are common among patients receiving ART at the time of admission and throughout the hospital course. Interventions including medication review by clinical pharmacists are critical in the prevention of CSDDIs on admission.

Rapid reduction in HIV viral load in late pregnancy with raltegravir: a case report.

The use of raltegravir (RAL) is not preferred to prevent perinatal transmission in pregnancy due to lack of safety and pharmacokinetic data in this population. Data have been limited to few case reports of patients who present for treatment late in pregnancy, have multidrug resistance, or have poor adherence, requiring an additional class such as an integrase inhibitor to further lower viral load. This case report describes and supports the initiation of RAL in very late pregnancy (week 33) to rapidly decrease viral load and successfully prevent perinatal transmission. By increasing the efficacy and safety data of RAL use in pregnancy, we believe this report can help provide some guidance on the management of complex cases.

Apparent interaction between telaprevir and warfarin in a patient with chronic hepatitis C viral infection.

PURPOSE: A probable interaction between warfarin and a recently approved protease inhibitor used in a triple-drug regimen for hepatitis C virus (HCV) infection is reported. SUMMARY: A 45-year-old Hispanic man seen at an anticoagulation clinic was found to have an International Normalized Ratio (INR) of 6.0; for the preceding eight months, INR values in the therapeutic range (2.5-3.5) had been maintained on a stable regimen of warfarin sodium 6 mg daily. Two days before the clinic visit, triple therapy with peginterferon alfa-2a, ribavirin, and telaprevir had been initiated for chronic HCV infection. The patient was instructed to skip two warfarin sodium doses and then resume its use at a reduced daily dose (5 mg), but he reported missing five doses, resulting in a below-target INR. An increase in the weekly warfarin dose of 50% above the baseline dose was required to reattain a target INR. The warfarin dosing requirement began to decline only after the man finished the prescribed 12-week course of telaprevir. CONCLUSION: The INR of an HCV-infected man who was on a stable warfarin regimen was found to be above the target range two days after triple therapy including telaprevir was begun. The INR fell below the target range after warfarin therapy was ceased for five days and returned to that range after warfarin was restarted and its dosage gradually increased to 1.5 times the baseline dosage. The warfarin dosage needed to maintain a target INR fell to nearly its baseline level after telaprevir was discontinued.