Posts filed under ‘Antivirales no HIV’

IDSA/AASLD Response to Cochrane Review on Direct-Acting Antivirals for Hepatitis C

Clinical Infectious Diseases December 2017 V.65 N.11

EDITOR’S CHOICE

William G Powderly; Susanna Naggie; Arthur Y Kim; Hugo E Vargas; Raymond T Chung …

A recent Cochrane Review with the stated objective to assess the benefits and harms of direct-acting antiviral (DAA) therapy for people with chronic hepatitis C virus (HCV) infection raised alarms within the hepatology and infectious diseases communities because the authors concluded that there was insufficient evidence to confirm or reject an effect of DAA therapy on HCV-related morbidity (cirrhosis, hepatic decompensation, or hepatocellular carcinoma) or all-cause mortality [1]. The authors also concluded that the clinical relevance of sustained virological response (SVR) obtained with DAAs is questionable, as it is a nonvalidated surrogate outcome. The Review further stated that because all DAA trials and outcome results were at high risk of bias, their results presumably overestimated benefit and underestimated harm. Indeed, the plain language summary stated that the lack of valid evidence and the possibility of potentially harming people with chronic hepatitis should be considered before treating people with hepatitis C using DAAs. Based on the findings of this Review, the authors concluded that additional randomized clinical trials are needed to assess the long-term clinical effects of DAAs…

PDF (hacer CLIC en PDF)

https://academic.oup.com/cid/article/65/11/1773/3965298

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November 29, 2017 at 8:21 am

The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries

Journal of Virus Eradication July 2017

Andrew M Hill1* , Sanjay Nath2 , Bryony Simmons2

1 Department of Translational Medicine, University of Liverpool, UK

2 Faculty of Medicine, Imperial College London, UK

Abstract

Background

Hepatitis C (HCV) can only be eradicated if annual rates of cure (SVR) are consistently and significantly higher than new HCV infections, across many countries. In 2016, the WHO called for a 90% reduction in new HCV infection by 2030. Direct-acting antivirals (DAA) can cure the majority of those treated, at around 90% in most populations, at potentially very low prices. We compared the net annual change in epidemic size across 91 countries using data on SVR, new HCV infections, and deaths. In a further 109 countries, we projected this figure using regional averages of epidemic size.

Methods

Epidemiological data for 2016 were extracted from national reports, publications and the Polaris Observatory. There were 91/210 countries with data on SVR, HCV-related deaths and new infections available for analysis; 109 countries had net change in epidemic size projected from the regional prevalence of HCV, extrapolated to their population size. ‘Net cure’ was defined as the number of people with SVR, minus new HCV infections, plus HCV-related deaths in 2016.

Results

For the 91 countries analysed, there were 57.3 million people with chronic HCV infection in 2016. In the remaining 109 countries, the projected epidemic size was 12.2 million, giving a global epidemic size of 69.6 million. Across the 91 countries, there was a fall from 57.3 to 56.9 million people in 2017, a 0.7% reduction. The projected global net change was from 69.6 to 69.3 million, a 0.4% reduction. Ten countries had at least five times more people reaching SVR than new HCV infections, including Egypt and USA. In 47/91 countries, there were more HCV infections than SVR in 2016.

Conclusion

Very few countries are on target to achieve elimination of HCV as a public health problem by 2030. While the North American, North African/Middle East and Western European regions have shown small declines in prevalence, the epidemic is growing in sub-Saharan Africa and Eastern Europe. Far higher rates of DAA treatment are required for worldwide elimination of HCV.

FULL TEXT

http://viruseradication.com/journal-details/The_road_to_elimination_of_hepatitis_C:_analysis_of_cures_versus_new_infections_in_91_countries/

September 25, 2017 at 8:21 am

Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases April 2017 V.4 N.2

Philippe Lachance; Justin Chen; Robin Featherstone; Wendy I. Sligl

Background.

The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients.

Methods.

We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 antigenemia, or viral culture from blood or bronchoalveolar lavage. Selected patient-centered outcomes included mortality, duration of mechanical ventilation, need for renal replacement therapy (RRT), and nosocomial infections. Health resource utilization outcomes included intensive care unit and hospital lengths of stay.

Results.

Twenty-two studies were included. In our primary analysis, CMV reactivation was associated with increased ICU mortality (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.87–3.47), overall mortality (OR, 2.02; 95% CI, 1.60–2.56), duration of mechanical ventilation (mean difference 6.60 days; 95% CI, 3.09–10.12), nosocomial infections (OR, 3.20; 95% CI, 2.05–4.98), need for RRT (OR, 2.37; 95% CI, 1.31–4.31), and ICU length of stay (mean difference 8.18 days; 95% CI, 6.14–10.22). In addition, numerous sensitivity analyses were performed.

Conclusions.

In this meta-analysis, CMV reactivation was associated with worse clinical outcomes and greater health resource utilization in critically ill patients. However, it remains unclear whether CMV reactivation plays a causal role or if it is a surrogate for more severe illness.

PDF

https://watermark.silverchair.com/api/watermark?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdcwggHTBgkqhkiG9w0BBwagggHEMIIBwAIBADCCAbkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMgS29QRsi_OI3SkaMAgEQgIIBigRs9nl2ylsVhYS_sYzV1Exhw5kNEVc_CDMHi9al85en5nmbiM0fSguSAPaX7eVjsRODgkAPeEpkpHFXtT5ee2umJp97CEvGaAbkiVReIdzG4W2RNfMvE2sN1dsphR2nXEn42SJyigJqE4fzz8cIaXZ_D-EACpZzDmIRmUo86ZcUsycSI2PzFbJFj19cTvvoID75bRPJGugrZ8SAfBf6V6-1IrrVl8xG1P7LAmi8eED3QPkcOjtAWOyzyW8WPYJ_5JOJPPAUzlNTmWAKP_9QjSg3NBavgOdzFrhwpzWnF7DYh5qVYp2bg2jrG3iXICmUVNPuC32npr3L2qEWvfmA4-_gQfRgRLvm8G42pCbdO1bBp5NGgHoMFnGHIlF3s-z4Xx7as7oIryKBJsd-MG9CE5kkL9d_x6nJLEr-WqRPZF6rmWl_0VWYfbOyAIn7u3OJrtX9NrLBsFWsmCxKa7Ghsvbvfkk9jpoerEn8x48ljyevLRq7bimX0gm-Vgo3GtltcVdajTLQ5-rUsEQ

September 3, 2017 at 6:43 pm

Editor’s Choice: Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don’t Change a Thing

Clinical Infectious Diseases January 1, 2017 V.64 N.1 P.92-99

Susanna Naggie, David P. Holland, Mark S. Sulkowski, and David L. Thomas

1Duke Clinical Research Institute

2Duke University School of Medicine, Durham, North Carolina

3Emory University School of Medicine, Atlanta, Georgia

4Johns Hopkins School of Medicine, Baltimore, Maryland

Currently, 380 000–400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures.

Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported.

We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP.

In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use.

PDF

https://cid.oxfordjournals.org/content/64/1/92.full.pdf+html

 

 

Clinical Infectious Diseases January 1, 2017 V.64 N.1 P.100-101

Editor’s Choice: Editorial Commentary: Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis

Joshua A. Barocas and Benjamin P. Linas

1Division of Infectious Diseases, Massachusetts General Hospital

2Boston University Schools of Medicine and Public Health

3Boston Medical Center, Massachusetts

In this issue of Clinical Infectious Diseases, Naggie et al discuss clinical decision making and present the results of a decision analysis examining the cost of hepatitis C virus (HCV) postexposure prophylaxis (PEP) among healthcare workers who experience a needlestick exposure to HCV-positive body fluids.

The authors discuss that, in an era when we can cure essentially all HCV infections, there are only 3 motivations for PEP. First, it may make sense to use PEP to prevent infections if doing so would decrease HCV transmission during the period of active HCV viremia. The paper succinctly reviews the evidence and quickly makes clear that among healthcare workers in the United States with a known HCV exposure, basic universal precautions reduce the risk of forward transmission to essentially zero.

A second motivation might be cost. Given that HCV medications are expensive, a shorter course PEP may be cost saving compared with full treatment for HCV infection. To address the possible economic rationale for PEP, the authors developed a decision tree to estimate the costs of PEP for HCV in a hypothetical cohort of 100 healthcare workers who had suffered a needlestick injury. They used the model to compare the outcomes with PEP to those with a strategy of “no PEP and treat only patients who develop chronic HCV infection.”

A few notable assumptions were made—namely, that PEP was 100% effective at preventing infection, while treatment for chronic HCV was only 98% effective with the first line of therapy. In addition, individuals who failed first-line treatment for chronic HCV infection were retreated with 100% . . .

PDF

https://cid.oxfordjournals.org/content/64/1/100.full.pdf+html

August 19, 2017 at 10:30 am

Oseltamivir Use Among Children and Adults Hospitalized With Community-Acquired Pneumonia.

Open Forum Infect Dis. Dec. 27, 2016 V.4 N.1

Oboho IK1,2, Bramley A1, Finelli L1, Fry A1, Ampofo K3, Arnold SR4,5, Self WH6, Williams DJ6, Courtney DM7, Zhu Y6, Anderson EJ8, Grijalva CG6, McCullers JA4,5, Wunderink RG7, Pavia AT3, Edwards KM6, Jain S1.

Author information

1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

2 Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia.

3 University of Utah Health Sciences Center, Salt Lake City.

4 Le Bonheur Children’s Hospital, Memphis, Tennessee.

5 University of Tennessee Health Science Center, Memphis.

6 Vanderbilt University School of Medicine, Nashville, Tennessee.

7 Northwestern University Feinberg School of Medicine, Chicago, Illinois.

8 Emory University School of Medicine, Atlanta, Georgia.

Abstract

BACKGROUND:

Data on oseltamivir treatment among hospitalized community-acquired pneumonia (CAP) patients are limited.

METHODS:

Patients hospitalized with CAP at 6 hospitals during the 2010-2012 influenza seasons were included. We assessed factors associated with oseltamivir treatment using logistic regression.

RESULTS:

Oseltamivir treatment was provided to 89 of 1627 (5%) children (<18 years) and 143 of 1051 (14%) adults. Among those with positive clinician-ordered influenza tests, 39 of 61 (64%) children and 37 of 48 (77%) adults received oseltamivir. Among children, oseltamivir treatment was associated with hospital A (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 1.36-4.88), clinician-ordered testing performed (aOR, 2.44; 95% CI, 1.47-5.19), intensive care unit (ICU) admission (aOR, 2.09; 95% CI, 1.27-3.45), and age ≥2 years (aOR, 1.43; 95% CI, 1.16-1.76). Among adults, oseltamivir treatment was associated with clinician-ordered testing performed (aOR, 8.38; 95% CI, 4.64-15.12), hospitals D and E (aOR, 3.46-5.11; 95% CI, 1.75-11.01), Hispanic ethnicity (aOR, 2.06; 95% CI, 1.18-3.59), and ICU admission (aOR, 2.05; 95% CI, 1.34-3.13).

CONCLUSIONS:

Among patients hospitalized with CAP during influenza season, oseltamivir treatment was moderate overall and associated with clinician-ordered testing, severe illness, and specific hospitals. Increased clinician education is needed to include influenza in the differential diagnosis for hospitalized CAP patients and to test and treat patients empirically if influenza is suspected.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413989/pdf/ofw254.pdf

July 16, 2017 at 11:44 am

New hepatitis C antiviral treatments eliminate the virus

Lancet July 8, 2017 V.390 N.10090

Correspondence

Joseph S Doyle, Alexander J Thompson, Peter Higgs, Mark Stoove, Paul M Dietze, Margaret E Hellard

The Cochrane Collaboration has published a topical systematic review1 and meta-analysis on direct-acting antivirals (DAA) for chronic hepatitis C virus (HCV) infection.

Jakobsen and colleagues1 compared the results of randomised trials of any HCV DAA regimen versus no intervention or placebo.

Their review reported data from 138 trials, which included 25 232 participants and encompassed all drugs on the market or under development.

The authors confirm treatment has a significant benefit (relative risk 0·44, 95% CI 0·37–0·52, p<0·001), compared with no treatment, in the elimination of the virus from the bloodstream, measured 12–24 weeks after treatment (sustained virological response, SVR); however, they conclude there was “insufficient evidence to judge if DAAs have beneficial or harmful effects on other clinical outcomes for chronic HCV” and that although DAAs might increase SVR, “the clinical implication of the results on this non-validated surrogate outcome is unclear”…..

FULL TEXT

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31817-2/fulltext?elsca1=etoc

PDF

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)31817-2.pdf

July 7, 2017 at 8:04 am

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

Journal of Infectious Diseases May 15, 2017 V.215 N.10 P.1514-1522

EDITOR’S CHOICE

Michael Boeckh  Terry Stevens-Ayers  Giovanna Travi  Meei-Li Huang  Guang-Shing Cheng Hu Xie  Wendy Leisenring  Veronique Erard  Sachiko Seo  Louise Kimball  …

Background.

Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding.

Methods.

We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR.

Results.

Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values.

Conclusion.

CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/215/10/10.1093_infdis_jix048/3/jix048.pdf?Expires=1499397143&Signature=ZGqgqbQ9a2uE12bomeqsVGChCW1Y3N54DapASFYI-SwrBn~eaUCXlNiXdKohVR-mw9Lx4NsjrxxqpIuvbiiGy8rpCb0sOLHdUlt8eA-mB7oZe249GgBvS8Oz9pXG-D7qBtEJ3jMI235GXMaYneGNv50wGHU6Nu3jzmffhXrz9GqjXrO5u80MlMtQDeB3DtOQVMl5vF4~dLL4o~OSWN4hI6gwqaR998s1l5iSspqNsU4suq4TmFlwcNLrmBpSA8z8XRVsKsS~7RrBDsGENU5SDxXp1AZmY50mHB3fvKjpnLXPdvQdedi3wHLfereEU5i7PaZ3MBlPz-RvtbGiMXjMUA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

July 5, 2017 at 10:24 pm

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