Agnes Cha

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.

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.

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 pharmacists 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

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

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.

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

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.

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

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

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.

Sofosbuvir: A New Oral Once-Daily Agent for The Treatment of Hepatitis C Virus Infection

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.