Archive for August, 2015

Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes

Journal of Infect Dis August 1, 2015 V.212 N.3 P.367-377

Editor’s Choice

Zobair M. Younossi, Maria Stepanova, Mark Sulkowski, Susanna Naggie, Massimo Puoti, Chloe Orkin, and Sharon L. Hunt

1Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital

2Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia

3Center for Outcomes Research in Liver Diseases, Washington, D.C.

4John Hopkins University, Baltimore, Maryland

5Duke Medical Center, Durham, North Carolina

6Division of Infectious Diseases, AO Ospedale Niguarda Ca’ Granda, Milan, Italy

7Barts Health NHS Trust, London, United Kingdom

Correspondence: Zobair M. Younossi, MD, MPH, Betty and Guy Beatty Center for Integrated Research, Claude Moore Health Education and Research Bldg, 3300 Gallows Rd, Falls Church, VA 22042 (


Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients. We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection.


HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated. All subjects completed standard PRO questionnaires before, during, and after treatment.


Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients. During treatment, moderate decrements in PRO scores (change, up to −6.8% on a 0%–100% scale; P = .0053) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation, most PRO scores improved (change, up to +7.6%; P < .0001), similar to findings for HCV-monoinfected patients. In multivariate analysis, in addition to clinico-demographic predictors, coinfection with HIV was associated with PRO impairment at baseline (beta, up to −7.6%; P < .002) but not with treatment-emergent changes in PRO scores (all P > .05).


Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and, despite the presence of some baseline impairment, have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection.

Clinical Trials Registration.NCT01667731 (PHOTON-1), NCT01783678 (PHOTON-2), NCT01604850 (FUSION), and NCT01682720 (VALENCE).


August 31, 2015 at 1:20 pm

Hepatitis C Virus Infection Is Systemic: Meeting Additional Goals

Journal of Infect Dis August 1, 2015 V.212 N.3 P.343-344

Editor’s Choice

Rushabh Modi and Sammy Saab

1Department of Medicine

2Department of Surgery, University of California, Los Angeles

Correspondence: Sammy Saab, MD, MPH, Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plz, Ste 214, Los Angeles, CA 90095 (

Chronic hepatitis C virus (HCV) infection is a major public health concern in the United States.

HCV infection is the leading cause of cirrhosis and the most common indication for liver transplantation. There is growing appreciation that HCV infection is a systemic infection and does not only cause liver disease.

For instance, health-related quality of life (HRQL) may be notably diminished, even in the absence of overt complications of liver dysfunction.

Patient-reported outcomes (PROs) represent a systematic attempt to quantify the subjective experience of illness. Self-perceptions of health predict mortality and morbidity, as well as enhance the patient-provider relationship …..


August 31, 2015 at 1:18 pm

Editor’s Choice: Inflammation in Chronic HIV Infection: What Can We Do?

Journal of Infect Dis August 1, 2015 V.212 N.3 P.339-342

Kristine M. Erlandson and Thomas B. Campbell

Department of Medicine, Division of Infectious Diseases, University of Colorado, Aurora

Correspondence: Kristine M. Erlandson, MD, MS, 12700 E 19th Ave, Mail Stop B168, Aurora, CO 80045 (

Effective antiretroviral therapy (ART) has dramatically improved the life expectancy of persons living with human immunodeficiency virus (HIV).

However, even with long-term, effective ART, HIV-infected persons have persistent, low-grade inflammation and immune activation [1] that are strongly associated with a heightened risk for cardiovascular disease [2–4], osteoporosis [5], anemia [6], physical function impairments and frailty [7], among other non-AIDS–defining events and mortality [8, 9].

For example, a recent analysis in the Multicenter AIDS Cohort Study found that levels of soluble CD14 (sCD14), a marker of monocyte activation, were significantly higher in HIV-infected men, compared with HIV-uninfected men, but that they did not differ between HIV-infected men with and those without effective ART and changed very little in the years following ART initiation [10].

Given the long-term consequences of chronic inflammation, there is an urgent need to better understand the causes and develop interventions that attenuate the effects of inflammation and immune activation in people living with HIV infection.

The study by Hileman et al in this issue of The Journal of Infectious Diseases offers insight into how the choice of the initial antiretroviral regimen affects subsequent changes in inflammation and immune activation markers…


August 31, 2015 at 1:17 pm

Evolving Resistance Among Gram-positive Pathogens

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S48-S57

Jose M. Munita, Arnold S. Bayer, and Cesar A. Arias

1Division of Infectious Diseases, Department of Internal Medicine

2Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston

3Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance

4David Geffen School of Medicine at UCLA, Los Angeles, California

5International Center for Microbial Genomics

6Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia

7Clinica Alemana de Santiago, Universidad del Desarrollo, Chile

Correspondence: Cesar A. Arias, MD, PhD, University of Texas Medical School at Houston, 6431 Fannin St, MSB 2.112, Houston, TX 77030 (

Antimicrobial therapy is a key component of modern medical practice and a cornerstone for the development of complex clinical interventions in critically ill patients.

Unfortunately, the increasing problem of antimicrobial resistance is now recognized as a major public health threat jeopardizing the care of thousands of patients worldwide.

Gram-positive pathogens exhibit an immense genetic repertoire to adapt and develop resistance to virtually all antimicrobials clinically available. As more molecules become available to treat resistant gram-positive infections, resistance emerges as an evolutionary response.

Thus, antimicrobial resistance has to be envisaged as an evolving phenomenon that demands constant surveillance and continuous efforts to identify emerging mechanisms of resistance to optimize the use of antibiotics and create strategies to circumvent this problem.

Here, we will provide a broad perspective on the clinical aspects of antibiotic resistance in relevant gram-positive pathogens with emphasis on the mechanistic strategies used by these organisms to avoid being killed by commonly used antimicrobial agents.


August 30, 2015 at 3:29 pm

Telavancin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Clinical Infectious Diseases SEP 15, 2015 V.61 Suppl.2 S35-S37

Keith A. Rodvold

Colleges of Pharmacy and Medicine, University of Illinois at Chicago

Correspondence: Keith A. Rodvold, PharmD, FCCP, FIDSA, University of Illinois at Chicago, College of Pharmacy, M/C 886, 833 S Wood St, Rm 164, Chicago, IL 60612 (

Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide range of infections, including skin and skin-structure infections, pneumonia, bloodstream infections, and endocarditis [1].

Staphylococci, including MRSA, are considered to be a leading cause of healthcare-associated infections [2]. Many of these infections can be life-threatening and cause sepsis and death.

The Centers for Disease Control and Prevention estimate that 80 461 severe MRSA infections and 11 285 MRSA-related deaths occur each year in the United States [2].

The changing epidemiology and increasing prevalence of resistant phenotypes of S. aureus, including MRSA, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and, rarely, vancomycin-resistant S. aureus, have spurred the need for new antimicrobial agents to treat serious infections caused by these gram-positive pathogens.


Telavancin is a semisynthetic lipoglycopeptide antibacterial with potent bactericidal activity against a broad spectrum of these gram-positive organisms, including MRSA [3].

The recommended dosage regimen for telavancin is 10 mg/kg body weight intravenously infused over a 60-minute period every 24 hours in patients with normal renal function (creatinine clearance [CrCl], >50 mL/min).

A dosage adjustment is required for patients with renal impairment (CrCl, ≤50 mL/min). This supplement provides historical and current perspectives on the present roles of telavancin in clinical practice.



August 30, 2015 at 3:26 pm

Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response

Clinical Infectious Diseases SEP 15, 2015 V.61 N.5 P.730-740

Bryony Simmons, Jawaad Saleem, Katherine Heath, Graham S. Cooke, and Andrew Hill

1Division of Medicine, Imperial College London

2Pharmacology and Therapeutics, Liverpool University, United Kingdom

Correspondence: Bryony Simmons, MPH, St Mary’s Campus, Imperial College London, Norfolk Place, London W2 1PG, UK (


Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations.


An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated.


31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9–7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37–.67) in the general population, 0.26 (95% CI, .18–.74) in the cirrhotic group, and 0.21 (.10–.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations.


The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus.


August 30, 2015 at 3:23 pm

Pseudomonas aeruginosa Eradication: How Do We Measure Success?

Clinical Infectious Diseases SEP 1, 2015 V.61 N.5 P.716-718

Editorial Commentary

Edith T. Zemanick and Theresa A. Laguna

1Department of Pediatrics, University of Colorado School of Medicine, Aurora

2Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis

Correspondence: Edith T. Zemanick, MD, MSCS, Department of Pediatrics, University of Colorado School of Medicine, 13123 E 16th Ave B-395, Aurora, CO 80045 (

Lung disease remains the major cause of morbidity and mortality for people living with cystic fibrosis (CF) [1].

Dysfunctional chloride conductance in the airways results in impaired mucus clearance, which drives a vicious cycle of infection, inflammation, and airway destruction.

Pseudomonas aeruginosa (Pa) is a bacterial pathogen largely feared by the CF community as its chronic presence is associated with lung damage, a more rapid decline in lung function, and earlier mortality [2–6]. Unfortunately, Pa in airway secretions will be cultured in 80% of people with CF by age 18 years.


August 29, 2015 at 7:36 pm

The Effect of Universal Glove and Gown Use on Adverse Events in Intensive Care Unit Patients

Clinical Infectious Diseases AUG 15, 2015 V.61 N.4 P.545-553

Editor’s Choice

Lindsay D. Croft, Anthony D. Harris, Lisa Pineles, Patricia Langenberg, Michelle Shardell, Jeffrey C. Fink, Linda Simoni-Wastila, and Daniel J. Morgan for the Benefits of Universal Glove and Gown (BUGG) Primary Investigators

1Department of Epidemiology and Public Health, University of Maryland School of Medicine

2VA Maryland Healthcare System

3Department of Medicine, Division of General Internal Medicine, University of Maryland School of Medicine

4Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore

Correspondence: Daniel J. Morgan, MD, MS, Department of Epidemiology and Public Health, University of Maryland School of Medicine, 685 W Baltimore St, MSTF 334, Baltimore, MD 21201 (


No randomized trials have examined the effect of contact precautions or universal glove and gown use on adverse events. We assessed if wearing gloves and gowns during all patient contact in the intensive care unit (ICU) changes adverse event rates.


From January 2012 to October 2012, intervention ICUs of the 20-site Benefits of Universal Gloving and Gowning cluster randomized trial required that healthcare workers use gloves and gowns for all patient contact. We randomly sampled 1800 medical records of adult patients not colonized with antibiotic-resistant bacteria and reviewed them for adverse events using the Institute for Healthcare Improvement Global Trigger Tool.


Four hundred forty-seven patients (24.8%) had 1 or more ICU adverse events. Adverse events were not associated with universal glove and gown use (incidence rate ratio [IRR], 0.81; 95% confidence interval [CI], .48–1.36). This did not change with adjustment for ICU type, severity of illness, academic hospital status, and ICU size, (IRR, 0.91; 95% CI, .59–1.42; P = .68). Rates of infectious adverse events also did not differ after adjusting for the same factors (IRR, 0.75; 95% CI, .47–1.21; P = .24).


In ICUs where healthcare workers donned gloves and gowns for all patient contact, patients were no more likely to experience adverse events than in control ICUs. Concerns of adverse events resulting from universal glove and gown use were not supported. Similar considerations may be appropriate regarding use of contact precautions.

Clinical Trials Registration. NCT0131821.


August 29, 2015 at 7:34 pm

Editorial Commentary: Getting Smart in How We Pay for HCV Drugs: KAOS vs CONTROL

Clinical Infectious Diseases JUL 15, 2015 V.61 N.2 P.169-170

Editor’s Choice

Center for AIDS Research, University of Alabama at Birmingham

Correspondence: Michael S. Saag, MD, Director, Center for AIDS Research, University of Alabama at Birmingham, 845 – 19th St South, Birmingham, AL 35294-2107 (

Over the last 2 years a therapeutic revolution has been occurring for the treatment of hepatitis C virus (HCV) infections. Direct acting antiviral (DAA) agents that allow all-oral regimens have been released.

These regimens replace the use of injectable peginterferon, which markedly reduce adverse effects, significantly reduce the duration of treatment (eg, from 48 weeks to 12 weeks), and increase cure rates from 60% to 70% to greater than 95% in most clinical scenarios [1].

Based on this set of facts alone, a clear message is that virtually every patient with chronic HCV should be treated [2]. Now.

As the new HCV agents were released, however, the price-tag of the drugs created sticker shock, especially among the payers who were not fully prepared to treat so many patients at one time with such expensive medications.

To keep expenditures under control, payers questioned the need to treat patients with less advanced disease (eg, those with F0- F2 fibrosis), owing to the uncertainty of who will progress (less than 50% of patients develop cirrhosis over 30 years) and the relatively slow progression of disease among those who do progress.

The payer’s reluctance to pay for drugs created barriers for patients and providers to gain access to therapy. All involved called out for data on the cost-effectiveness of the new all oral regimens, which heretofore did not exist.

In this issue of CID, Rein and colleagues provide, for the first time, the cost-effectiveness data for …



August 29, 2015 at 7:32 pm

The Cost-effectiveness, Health Benefits, and Financial Costs of New Antiviral Treatments for Hepatitis C Virus

Clinical Infectious Diseases JUL 15, 2015 V.61 N.2 P.157-168

Editor’s Choice

David B. Rein, John S. Wittenborn, Bryce D. Smith, Danielle K. Liffmann, and John W. Ward

1Public Health Department, NORC at the University of Chicago, and

2Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia

Correspondence: David B. Rein, PhD, NORC at the University of Chicago, Public Health Department, 3520 Piedmont Rd NE, Ste 225, Atlanta, GA 30305 (


New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown.


We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective.


Compared to treatment with pegylated interferon and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths by 80 682, and increased costs by $26.2 billion at an ICER of $47 304 per QALY gained. As compared to PRS/SR, treating with an all oral regimen of Sofosbuvir and Simeprevir (SS) for G1/4 and SR for G2/3, increased QALYs by 1 110 451 and reduced deaths by an additional 164 540 at an incremental cost of $80.1 billion and an ICER of $72 169. In sensitivity analysis, where treatment with SS effectiveness was set to the list price of Viekira Pak and then Harvoni, treatment cost $24 921 and $25 405 per QALY gained as compared to PRS/SR.


New treatments are cost-effectiveness per person treated, but pent-up demand for treatment may create challenges for financing.


August 29, 2015 at 7:30 pm

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