CD4+ T-cell recovery in HIV/hepatitis C co-infected patients following successful hepatitis C treatment.

INTRODUCTION: Hepatitis C virus (HCV)/HIV co-infection has been identified as a risk for impaired CD4+ T-cell recovery, possibly mediated by HCV-induced liver fibrosis and/or immune activation. As HCV direct-acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA-induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non-responders [INRs]). METHODS: Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre-DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre-DAA period (-36 months) versus the post-DAA period (+36 months). RESULTS: In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6-month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6-month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6-month time interval [p = 0.02]). In total, 54% of INRs recorded a post-DAA CD4 count of >350 cells/mm3. CONCLUSIONS: Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery.

A Comprehensive Review of Herbal Supplements Used for Persistent Symptoms Attributed to Lyme Disease.

Context: Lyme disease is the most common, tick-borne disease in the USA. While most patients successfully recover with antibiotics, some patients experience persistent symptoms for months to years. Patients who attribute chronic symptoms to Lyme disease commonly use herbal supplements. The complexity, variability in dose and formulation, and lack of data for these herbal compounds make it difficult to assess their efficacy and safety. Objective: This review examines the evidence for the antimicrobial activity, safety, and drug-drug interactions of 18 herbal supplements that patients commonly use for treatment of persistent symptoms attributed to Lyme disease. Design: The research team performed a narrative review by searching the PubMed, Embase, Scopus, Natural Medicines databases, and NCCIH website. The search used the keywords for 18 herbal compounds: (1) andrographis (Andrographis paniculate), (2) astragalus (Astragalus propinquus), (3) berberine, (4) cat's claw bark (Uncaria tomentosa), (5) cordyceps (Cordyceps sinensis), (6) cryptolepis (Cryptolepis sanguinolenta), (7) Chinese skullcap (Scutellaria baicalensis), (8) garlic (Allium sativum), (9) Japanese knotwood (Polygonum cuspidatum), (10) reishi mushrooms (Ganoderma lucidum), (11) sarsaparilla (Smilax medica), (12) Siberian ginseng (Eleutherococcus senticosus), (13) sweet wormwood (Artemisia annua), (14) teasle root (Dipsacus fullonum), (15) lemon balm (Melissa officinalis), (16) oil of oregano (Origanum vulgare), (17) peppermint (Mentha x piperita), and (18) thyme (Thymus vulgaris). The team also searched for terms related to protocols, including Dr. Rawls' protocol and the Buhner protocol. Setting: University of Maryland Medical Center, Baltimore MD. Results: Seven of the 18 herbs reviewed had evidence for in-vitro activity against B. burgdorferi. These compounds included: (1) cat's claw (2) cryptolepis, (3) Chinese skullcap, (4) Japanese knotweed, (5) sweet wormwood, (6) thyme, and (7) oil of oregano. With the exception of oil of oregano these compounds also have anti-inflammatory activity. In vivo data and clinical trials are lacking. Clinicians should be cautious as many of the identified compounds have drug interactions and additive effects that could lead to increased risks for bleeding, hypotension, and hypoglycemia. Conclusions: Many of the herbs that alternative and integrative practitioners use to treat Lyme disease have anti-inflammatory effects that may contribute to patients' perceptions of symptomatic improvement. Some herbs have limited demonstrated anti-borrelial activity in vitro, but in-vivo data and clinical trial data is lacking. Further research is required to determine the efficacy, safety and appropriate use of these herbs for this patient population.

Interprofessional Culinary Medicine Training Enhanced Nutrition Knowledge, Nutrition Counseling Confidence, and Interprofessional Experience.

Introduction: Culinary medicine training combining evidence-based nutrition instruction with experiential cooking application has improved nutrition knowledge, skills, and attitudes in the professional and personal lives of medical students. However, interprofessional culinary training remains largely unstudied among professional students who will be involved in collaborative patient care. The goal of this study was to evaluate the feasibility and effectiveness of an elective interprofessional culinary medicine course for students in the medical, pharmacy, social work, nursing, law, and dentistry schools at the University of Maryland, Baltimore. Methods: The interprofessional culinary medicine course was offered in-person at the teaching kitchen of the Nova Institute for Health in 2020 and virtually in 2021 during the COVID pandemic. The training featured five workshops combining instruction in a variety of popular diets, cooking a meal inspired by the diet in focus, and group discussion. Paired t tests were utilized to evaluate changes in pre-/post-training nutrition and interprofessional experience outcomes. Linear regression models were constructed to compare outcomes between in-person and virtual delivery. Results: A total of 62 students participated in the culinary medicine training. Confidence in all nutrition knowledge, skills, and attitudes, as well as interprofessional experience outcomes, improved after the training (p < 0.05). Similar improvements were noted in most outcomes with in-person and virtual delivery in linear regression modeling. Discussion: Interprofessional culinary medicine training is feasible, and virtual delivery may help enhance replicability in other settings.

Utility of On-Treatment Viral Loads During Treatment With Direct-Acting Antivirals in Patients Infected With Chronic Viral Hepatitis C.

Background: Direct-acting antiviral (DAA) agents have revolutionized the treatment of chronic hepatitis C virus (HCV) infection. Current data regarding the utility of on-treatment HCV viral load (VL) monitoring are conflicting and limited data are available in HIV-coinfected patients. Objective: The objective of the study was to determine whether on-treatment VLs are predictive of HCV cure in a real-world population. Method: A single-center, retrospective cohort study was conducted using patients who received a prescription for DAA therapy for HCV treatment at a large, tertiary ambulatory care clinic. Results: A total of 219 patients were included in the final analysis. The average age was 56 years. Most patients were male (64.4%), African American (73.1%), and insured by Medicaid (61.6%). Most patients were treatment-naive, noncirrhotic, and infected with HCV genotype 1a (73.1%). About 22.4% of patients were coinfected with HIV. The most common regimen was 12 weeks of ledipasvir/sofosbuvir (53.9%). On-treatment VLs were most commonly obtained at treatment week 4 (42.5%), of which 45.2% of patients were detectable. Sustained virologic response (SVR) was achieved in 96.8% of the total population and 95.9% of HIV-coinfected patients. Of the 7 patients who did not achieve SVR, 3 patients had undetectable on-treatment VLs in the first 8 weeks of therapy. Conclusion: Sustained virologic response rates were similar between HCV-monoinfected patients and HCV-HIV-coinfected patients. This research further supports that on-treatment VLs may not be a valuable indicator of treatment failure but may be helpful to engage patients in care and ensure treatment adherence and ultimately cure.

Health Care Resource Utilization Associated With Parkinson Disease Among Medicare Beneficiaries.

OBJECTIVE: To compare differences in health care resource utilization (HcRU) over time between Medicare beneficiaries with and without Parkinson disease (PD). METHODS: This retrospective observational study used the Chronic Conditions Data Warehouse (5% Medicare sample) between 2005 and 2015. In a propensity score-matched (age, sex, race, and comorbidity adjusted) sample of beneficiaries with and without PD, we examined all-cause HcRU due to inpatient admissions, emergency department (ED) admissions, skilled nursing facility (SNF) admissions, health care provider encounters, neurologist visits, rehabilitation service visits, and non-PD medication fills. Relative to beneficiaries without PD, we reported adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for beneficiaries with PD using generalized linear models with log link and negative binomial variance functions. RESULTS: A total of 467,064 Medicare enrollees (unmatched sample) met the inclusion criteria. Of these, 3.3% had PD. In the matched sample and relative to beneficiaries without PD, beneficiaries with PD displayed higher rates of inpatient admissions (IRR 1.29, 95% CI 1.24-1.34), ED admissions (IRR 1.31, 95% CI 1.27-1.34), SNF admissions (IRR 2.00, 95% CI 1.92-2.09), health care provider encounters (IRR 1.18, 95% CI 1.16-1.20), neurologist visits (IRR 5.57, 95% CI 5.35-5.78), rehabilitation service visits (IRR 1.47, 95% CI 1.41-1.53), and non-PD medication fills (IRR 1.10, 95% CI 1.08-1.11) over time. CONCLUSION: These results reflect patterns of medical care among Medicare beneficiaries with PD. The findings can help clinicians, payers, and policy makers make evidence-based decisions for the allocation of scarce health care resources for PD management. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that Medicare beneficiaries with PD use more health care resources than matched controls without PD.

Effectiveness of 8 weeks of ledipasvir/sofosbuvir for hepatitis C in HCV-HIV-coinfected patients.

BACKGROUND: Data is limited on the use of 8 weeks of therapy with ledipasvir/sofosbuvir (LDV/SOF) for special populations such as HCV-HIV-coinfected patients. The primary objective of this analysis was to compare sustained virological response at 12 weeks after end of therapy (SVR12) rates among HCV-monoinfected and HCV-HIV-coinfected patients in a real-world clinical setting. Additionally, we compared SVR12 rates among patients receiving 8 versus 12 weeks of therapy. METHODS: This was a single-centre, retrospective study of HCV-infected patients prescribed LDV/SOF at ambulatory clinics associated with the University of Maryland Medical Center (UMMC) from May 2015 to May 2016. Data were obtained from UMMC electronic medical records and outpatient pharmacy claims database. Comparisons between groups were made using χ2 or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon rank-sum for continuous variables. All analyses were per-protocol; patients missing SVR12 data (25.2%) could not be evaluated for our stated objectives. RESULTS: A total of 274 patients were included. Median age was 58 years; 62.8% were male; 82.5% were Black. SVR12 data was available for 65 HCV-HIV-coinfected patients, of which 62 (95.4%) achieved SVR12. There was no difference in SVR12 rate between HCV-HIV-coinfected patients and HCV-monoinfected patients (86/90; 95.6%; P=0.959). Additionally, there was no difference in SVR12 attainment between HIV-HCV-coinfected patients who received 8 versus 12 weeks of therapy (P=0.101). CONCLUSIONS: 8 weeks of LDV/SOF was effective for treatment-naive, non-cirrhotic, HCV genotype-1 patients in this real-world setting, regardless of HIV status. Increased uptake of the 8-week regimen can decrease costs for patients and payers without compromising outcomes.

Direct-Acting Antivirals to Prevent Vertical Transmission of Viral Hepatitis C: When Is the Optimal Time to Treat?

OBJECTIVE: To describe the most current evidence for the use of direct-acting antivirals (DAAs) to treat hepatitis C along the pregnancy-pediatric continuum in the United States. DATA SOURCES: The MEDLINE/PubMed databases were searched (January 1995 to February 2018) for articles in English using the terms: hepatitis C, vertical transmission, pregnancy, pediatrics, ribavirin, interferon, direct acting antivirals, daclatasvir, dasabuvir, elbasvir, glecaprevir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, pibrentasvir, simeprevir, sofosbuvir, and velpatasvir. STUDY SELECTION AND DATA EXTRACTION: All relevant studies, meta-analyses, systematic reviews, guidelines, and review articles were evaluated for inclusion. References from pertinent articles were assessed for additional content that was not found during the initial search. DATA SYNTHESIS: The primary route of transmission for hepatitis C virus (HCV) in pediatric patients is vertical transmission (VT), with the rate estimated to be 5.8%. Screening for HCV during pregnancy is not routinely part of clinical care, and the data for the use of DAAs in pregnancy is limited. A significant number of infected infants will clear the HCV infection spontaneously, and ledipasvir/sofosbuvir and sofosbuvir have recently been Food and Drug Administration approved for use in pediatric patients older than 12 years. CONCLUSIONS: Data to determine the best treatment point along the pregnancy-pediatric continuum are limited; however, given the lack of human data for use of DAAs during pregnancy, low rate of VT, high rate of spontaneous pediatric clearance, and recent approval of DAAs for pediatric patients, treatment of chronically infected children seems to be the optimal strategy currently.

Future Considerations for the Evaluation of Hepatitis C Virus Treatments in Pan-Genotypic Therapy for Noncirrhotic Treatment-Naive Patients.

Given the recent approval of the first pan-genotypic chronic hepatitis C virus (HCV) therapy, managed care, health systems, and clinicians will need to evaluate current practices related to essential laboratory assessments used to select therapy. Historically, clinicians and payers required a battery of tests to determine HCV genotype, viral load, degree of fibrosis, and organ function. In light of current and forthcoming approvals of pan-genotypic therapy, clinicians and payers can expect a more competitive marketplace and a downward curve in the price of therapy. Ultimately, this development will lead to the cost of screenings and assessments having an increased role in selecting an optimal HCV therapy. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. All authors contributed to study concept and design. Calabrese took the lead in data collection, along with Shaya. Data interpretation was performed by Calabrese and Hynicka, along with Rodriguez de Bittner and Shaya. The manuscript was written and revised by Calabrese and Hynicka, along with Rodriguez de Bittner and Shaya.

Evaluating a Collaborative Approach to Improve Prior Authorization Efficiency in the Treatment of Hepatitis C Virus.

OBJECTIVE: A team-based approach to obtaining prior authorization approval was implemented utilizing a specialty pharmacy, a clinic-based pharmacy technician specialist, and a registered nurse to work with providers to obtain approval for medications for hepatitis C virus (HCV) infection. The objective of this study was to evaluate the time to approval for prescribed treatment of HCV infection. METHODS: A retrospective observational study was conducted including patients treated for HCV infection by clinic providers who received at least 1 oral direct-acting antiviral HCV medication. Patients were divided into 2 groups, based on whether they were treated before or after the implementation of the team-based approach. Student t tests were used to compare average wait times before and after the intervention. RESULTS: The sample included 180 patients, 68 treated before the intervention and 112 patients who initiated therapy after. All patients sampled required prior authorization approval by a third-party payer to begin therapy. There was a statistically significant reduction (P = .02) in average wait time in the postintervention group (15.6 ± 12.1 days) once adjusted using dates of approval. CONCLUSIONS: Pharmacy collaboration may provide increases in efficiency in provider prior authorization practices and reduced wait time for patients to begin treatment.

Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein.

Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 pocket of the protein. Significantly, target molecules were accessed in just two synthetic steps, suggesting further optimization will require minimal synthetic effort. Molecular modeling using the Site-Identification by Ligand Competitive Saturation (SILCS) approach was used to qualitatively direct ligand design as well as develop quantitative models for inhibitor binding affinity to Mcl-1 and the Bcl-2 relative Bcl-xL as well as for the specificity of binding to the two proteins. Results indicated hydrophobic interactions in the p2 pocket dominated affinity of the most favourable binding ligand (3bl: Ki = 31 nM). Compounds were up to 19-fold selective for Mcl-1 over Bcl-xL. Selectivity of the inhibitors was driven by interactions with the deeper p2 pocket in Mcl-1 versus Bcl-xL. The SILCS-based SAR of the present compounds represents the foundation for the development of Mcl-1 specific inhibitors with the potential to treat a wide range of solid tumours and hematological cancers, including acute myeloid leukemia.

Are Fluoroquinolones Appropriate for the Treatment of Extended-Spectrum ß-Lactamase-Producing Gram-Negative Bacilli?

Objective: To review the data analyzing the role of fluoroquinolones in the treatment of extended-spectrum ß-lactamase (ESBL)-producing infections and rates and methods of co-transmission of resistance. Data Sources: A MEDLINE literature search was performed using the search terms extended-spectrum beta-lactamase, fluoroquinolone, ciprofloxacin, levofloxacin, plasmid transmission, and resistance from 1996 to June 2015. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language retrospective studies, prospective studies, and meta-analyses assessing efficacy of fluoroquinolone use in ESBL infections, assessing methods of resistance transmission, or analyzing patient risk factors were reviewed. Data Synthesis: A total of 18 studies that analyzed fluoroquinolone resistance and association to ESBL producing bacteria from either molecular or clinical perspectives were idenitifed. Four studies evaluated the genetic association between ESBL transmission and fluoroquinolone resistance. Plasmid mediated quinolone resistance was found in higher rates in ESBL-producing bacteria. Numerous studies analyzed the risk factors of co-occurring resistance identifying nosocomial acquired infections, recent hospitalization, long-term care facility residence, and intensive care unit stay as the most common. Conclusive clinical data are lacking; however, a meta-analysis showed fluoroquinolones had higher odds of all-cause mortality when used empirically to treat ESBL bacteremia compared with carbapenems. Conclusions: Fluoroquinolone resistance may be co-transmitted in ESBL-producing Enterobacteriaceae. There are limited data on the efficacy for fluoroquinolones in the treatment of ESBL-producing infections. Additional prospective trials are needed to definitively determine the role of fluoroquinolones in ESBL infections.

What does the pharmacological future of treating chronic hepatitis C look like?

Development of direct acting antivirals has revolutionized the standard of care for the treatment of hepatitis C virus. New interferon-free regimens provide sustained virologic response rates of >90% in many genotype 1 patients with only 12 weeks of oral therapy. This review will provide a brief overview of current standards of care with a summary of the evidence supporting the recommended combinations of direct acting antivirals. We will discuss the direction of future therapies, with strategies for shorter durations of therapy and new all-oral combinations in the pipeline.

Vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors.

OBJECTIVE: The prevalence of vancomycin-associated nephrotoxicity (VAN) is reported to vary from 1.0-42.6%, with most data from critically ill patients. Evaluation of VAN among internal medicine patients is lacking. Our objectives were to determine the incidence, time-course, outcomes, and risk factors of VAN in adult internal medicine patients. DESIGN: Retrospective cohort. SETTING: Tertiary care academic medical center. PATIENTS: A total of 125 adult internal medicine patients receiving vancomycin treatment with mean baseline creatinine clearance of 84.6 ± 27.6 ml/min. INTERVENTION: Vancomycin treatment for a minimum of 72 hours. MEASUREMENTS AND MAIN RESULTS: Nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dl or 50% above baseline (whichever was larger), occurred in 17 (13.6%) of 125 patients. No patients with VAN progressed to Loss or End stage as defined by the RIFLE criteria. The incidence rate of VAN was 0.02 cases/day of vancomycin treatment. Nephrotoxicity developed at a median of 4.5 days (interquartile range [IQR] 2.2-4.9) peaked at 5.7 days (IQR: 3.8-9.6), and resolved in 70.6% of the cases within 16.5 days (IQR: 6.0-17.8) after onset. On multivariable logistic regression analysis, after controlling for hypotensive episodes, Charlson Comorbidity Index, and baseline creatinine clearance, concomitant use of piperacillin-tazobactam was associated with increased VAN (adjusted odds ratio 5.36, 95% confidence interval 1.41-20.5). CONCLUSIONS: Vancomycin-associated nephrotoxicity is prevalent among internal medicine patients, with 5.36-fold higher odds if piperacillin-tazobactam is concomitantly administered.

Treatment strategy for a multidrug-resistant Klebsiella UTI.

OBJECTIVE: To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). CASE SUMMARY: A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in limited resolution of her symptoms. Colistin was started, however, therapy was discontinued on day 5 secondary to the development of acute kidney injury. Despite the short course of therapy, the patient's symptoms resolved. DISCUSSION: The case presented lends itself well to numerous discussion items that are important to consider when determining optimal treatment for MDR Gram-negative bacilli (GNBs). Susceptibility testing is an important tool for optimizing antibiotic therapy, however, automated systems may overestimate the susceptibility profile for a MDR GNB. Treatment strategies evaluated to treat MDR GNB, include combination therapy with a carbepenem and synergy using polymyxin. CONCLUSION: We have described the management strategy for a MDR Klebsiella UTI, the consequences of the initial management strategy, and potential strategies to manage these types of infections in future patients.

Prophylaxis of thromboembolic events in patients with nephrotic syndrome.

OBJECTIVE: To review published literature regarding use of strategies to prevent thrombotic events in patients with nephrotic syndrome (NS). DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were queried from 1980 to December 2012 for articles in English using the search terms nephrotic syndrome, thrombosis, thromboembolism, anticoagulation, warfarin, heparin, low-molecular-weight heparin, enoxaparin, dalteparin, tinzaparin, statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, aspirin, direct thrombin inhibitor, rivaroxaban, argatroban, lepirudin, bivalirudin, dabigatran, factor Xa inhibitor, fondaparinux, rivaroxaban, clopidogrel, ticlopidine, and prasugrel. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search. DATA SYNTHESIS: NS leads to multiple complications, including hypercoagulability. A small prospective cohort study used enoxaparin for primary prophylaxis and demonstrated successful prevention of thrombotic events with minimal adverse events. Additional information has come in the form of decision analyses, which show potential decreased morbidity and mortality when primary prophylaxis for thrombotic events is used; however, all data have numerous limitations. Other strategies for thrombus prevention, including statins and antiplatelet agents, also have been investigated. CONCLUSIONS: When patients with NS are admitted to the hospital, develop an acute medical illness, or acquire an additional thrombotic events risk factor such as surgery, active malignancy, or pregnancy, consideration for primary pharmacologic prophylaxis with appropriately dosed low-molecular-weight heparin or other indicated anticoagulant should include the potential for increased thrombotic events risk in this patient population. Consideration may also be given to the use of primary pharmacologic prophylaxis with low-molecular-weight heparin or oral vitamin K antagonist in patients with membranous nephropathy once the albumin level drops below 2.0-2.5 g/dL. Short-term use of pharmacologic prophylaxis during the first 6 months following diagnosis warrants further investigation.

Anemia management in patients with chronic viral hepatitis C.

OBJECTIVE: To review the literature regarding current strategies for the management of anemia associated with treatment for chronic viral hepatitis C (HCV) in adults. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched (January 1980-October 2012) for articles in English using the search terms anemia, ribavirin, dose reduction, erythropoietin stimulating agents, hepatitis C, HIV, liver transplant, telaprevir, and boceprevir. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search. DATA SYNTHESIS: Standard of care for patients infected with HCV genotype 1 now requires a triple therapy regimen including an HCV NS3 protease inhibitor. These regimens lead to significantly higher rates of anemia compared to prior dual therapy regimens. Development of an optimal management strategy should begin with risk stratification. Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80% of the initial ribavirin dose to achieve optimal sustained virologic response (SVR) with dual therapy. The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates. Limited data have been published regarding the management of anemia with triple therapy; however, efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia. CONCLUSIONS: Anemia is a common adverse event associated with the use of ribavirin, and, more recently, the new HCV protease inhibitors. Ribavirin dose reduction should continue to be used as an initial anemia management strategy, with the use of erythropoietin alfa 40,000 units once weekly reserved for patients whose hemoglobin does not adequately respond to initial management strategies.