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 (zobair.younossi@inova.org).

Background

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.

Methods

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.

Results

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).

Conclusions

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).

PDF

http://jid.oxfordjournals.org/content/212/3/367.full.pdf

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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 (ssaab@mednet.ucla.edu).

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 …..

PDF

http://jid.oxfordjournals.org/content/212/3/343.full.pdf

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 (kristine.erlandson@ucdenver.edu).

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…

PDF

http://jid.oxfordjournals.org/content/212/3/339.full.pdf

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 (cesar.arias@uth.tmc.edu).

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.

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S48.full.pdf

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 (kar@uic.edu).

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.

 

PDF

http://cid.oxfordjournals.org/content/61/suppl_2/S35.full.pdf

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 (bryony.simmons13@imperial.ac.uk).

Background

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.

Methods

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.

Results

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.

Conclusions

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.

PDF

http://cid.oxfordjournals.org/content/61/5/730.full.pdf

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 (edith.zemanick@childrenscolorado.org).

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.

PDF

http://cid.oxfordjournals.org/content/61/5/716.full.pdf

August 29, 2015 at 7:36 pm

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