This document discusses strategies for treating hepatitis C virus (HCV) infection in the next era of therapy. It summarizes discussions from a panel of international HCV experts on key questions regarding HCV treatment. One expert discussed whether a "one-size-fits-all" treatment approach is possible, noting that current data is moving in that direction with new all-oral regimens achieving high SVR rates across patient types. However, treatment may still need to be tailored to some degree for certain difficult-to-treat groups like genotype 3 patients with cirrhosis. The panel evaluated priorities for optimizing genotype 1 regimens and the potential role of shorter, simpler treatments. Management of treatment failures and how treatment may shift to primary
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
Estudios que evaluaron el tratamiento actual de la hepatitis C, los cuales fueron presentados en el consenso de viena en abril de 2015.
Forman parte de EASL guidelines HCV 2015.
Jill Blumenthal, M.D., of UC San Diego AntiViral Research Center, presents "International AIDS Conference 2014: A Moderately Rapid Review" at AIDS Clinical Rounds
Key Slides on Individualizing ART Management Based on Treatment Safety and To...hivlifeinfo
Обзор последних рекомендаций DHHS , индивидуализация лечения в отдельных группах пациентов, минимизация побочных эффектов и межлекарственных взаимодействий
Immunotherapy - the promises and pitfallsSCGH ED CME
This document discusses immunotherapy for cancer treatment and its promises as well as pitfalls. It provides examples of how immunotherapy has been successfully used to treat metastatic melanoma but can also cause immune-related side effects involving the thyroid, endocrine system, lungs, gut, liver, kidneys and skin. The document presents three case studies of patients who developed pneumonitis, colitis, and hepatitis, respectively, while undergoing immunotherapy and required treatment with steroids and other immunosuppressants. Management of immune-related toxicity from cancer immunotherapy requires specialist input.
Arv active-toxcity-monitoring-gaberone-training-workshop-on-managmentprempanigrahi
This document outlines key aspects of monitoring and managing adverse drug reactions related to antiretroviral therapies. It discusses WHO recommendations for antiretroviral drugs, defines important terms like adverse drug reactions and treatment limiting toxicities, and describes the major toxicities associated with different antiretroviral regimens as well as approaches for clinical management. It also covers recommendations for routine and active toxicity monitoring.
Оптимизация лечения ВИЧ в 2018 году / HIV Treatment Optimization: 2018hivlifeinfo
HIV Treatment Optimization: 2018
In this downloadable slideset, Eric S. Daar, MD, provides a comprehensive update on ART management.
Format: Microsoft PowerPoint (.ppt)
File Size: 723 KB
Released: April 26, 2018
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
Estudios que evaluaron el tratamiento actual de la hepatitis C, los cuales fueron presentados en el consenso de viena en abril de 2015.
Forman parte de EASL guidelines HCV 2015.
Jill Blumenthal, M.D., of UC San Diego AntiViral Research Center, presents "International AIDS Conference 2014: A Moderately Rapid Review" at AIDS Clinical Rounds
Key Slides on Individualizing ART Management Based on Treatment Safety and To...hivlifeinfo
Обзор последних рекомендаций DHHS , индивидуализация лечения в отдельных группах пациентов, минимизация побочных эффектов и межлекарственных взаимодействий
Immunotherapy - the promises and pitfallsSCGH ED CME
This document discusses immunotherapy for cancer treatment and its promises as well as pitfalls. It provides examples of how immunotherapy has been successfully used to treat metastatic melanoma but can also cause immune-related side effects involving the thyroid, endocrine system, lungs, gut, liver, kidneys and skin. The document presents three case studies of patients who developed pneumonitis, colitis, and hepatitis, respectively, while undergoing immunotherapy and required treatment with steroids and other immunosuppressants. Management of immune-related toxicity from cancer immunotherapy requires specialist input.
Arv active-toxcity-monitoring-gaberone-training-workshop-on-managmentprempanigrahi
This document outlines key aspects of monitoring and managing adverse drug reactions related to antiretroviral therapies. It discusses WHO recommendations for antiretroviral drugs, defines important terms like adverse drug reactions and treatment limiting toxicities, and describes the major toxicities associated with different antiretroviral regimens as well as approaches for clinical management. It also covers recommendations for routine and active toxicity monitoring.
Оптимизация лечения ВИЧ в 2018 году / HIV Treatment Optimization: 2018hivlifeinfo
HIV Treatment Optimization: 2018
In this downloadable slideset, Eric S. Daar, MD, provides a comprehensive update on ART management.
Format: Microsoft PowerPoint (.ppt)
File Size: 723 KB
Released: April 26, 2018
Современное лечение ВИЧ.Усилить или не усилить : преимущества и недостатки бу...hivlifeinfo
Современное лечение ВИЧ.Усилить или не усилить : преимущества и недостатки бустированных режимов АРТ / Contemporary Management of HIV.To Boost or Not to Boost-Advantages and Disadvantages of Boosted ART.2017
In this downloadable slideset, Eric S. Daar, MD, and Program Director Joseph J. Eron, Jr., MD, review advantages and disadvantages of boosted ART regimens for managing patients with HIV.
Format: Microsoft PowerPoint (.ppt)
File size: 514 KB
Date posted: 6/16/2017
Современное лечение ВИЧ.Обобщённые данные с конференции CROI 2020 / Contempor...hivlifeinfo
This document summarizes data presented at CROI 2020 on current and investigational antiretroviral therapies (ART) for HIV. Key findings include:
- A pooled analysis found the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was effective and well-tolerated in people over age 50 similar to younger patients.
- The switch to BIC/FTC/TAF was noninferior to remaining on baseline regimens even in people with baseline nucleoside reverse transcriptase inhibitor resistance.
- Through week 96, dolutegravir plus lamivudine was similarly effective
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014Hivlife Info
This document summarizes a presentation on new agents for treating hepatitis C virus (HCV) infection in patients coinfected with HIV. It discusses FDA-approved regimens containing simeprevir or sofosbuvir, dosing and administration, treatment guidelines from AASLD/IDSA, and clinical trial data on sofosbuvir and simeprevir in HIV/HCV coinfected patients, showing high sustained virologic response rates.
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супре...hivlifeinfo
This document discusses modifying antiretroviral therapy (ART) in virologically suppressed patients with HIV. It describes two phase 3 trials, ATLAS and FLAIR, that evaluated switching to long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) every 4 weeks in suppressed patients. Both trials found CAB/RPV to be noninferior to continued oral ART at 48 weeks. Common reasons to consider an ART switch include simplifying regimens or improving tolerability. Key factors that may increase risk of treatment failure with CAB/RPV include presence of rilpivirine resistance mutations at baseline and lower rilpivirine drug levels. The FDA
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
Современное лечение ВИЧ: новые парадигмы в АРТ / Contemporary Management of H...hivlifeinfo
Набор слайдов c рассмотрением важных вопросов об АРТ первого ряда, арв-препаратами пролонгированного действия и схемами АРТ с двумя препаратами, акцент в публикации на роль новых стратегий.
Expert Insights in Selecting a Switch Regimen for Virologically Suppressed HI...hivlifeinfo
Expert Insights in Selecting a Switch Regimen for Virologically Suppressed HIV-Infected Patients.2018
In this slideset, Babafemi Taiwo, MBBS, discusses expert approaches to selecting an HIV switch regimen in a series of cases studies involving HIV-infected patients with virologic suppression on their current ART regimen.
Format: Microsoft PowerPoint (.ppt)
File Size: 1.10 MB
HIV Alert :Updating Your Practice Based on New Guideline Recommendations.2016hivlifeinfo
In this downloadable slideset, Eric S. Daar, MD, and Paul E. Sax, MD, review recent updates to expert guideline recommendations for ART—including new initial therapy recommendations, revised guidance on switch strategies for virologically suppressed patients, and other key recommendation updates.
Format: Microsoft PowerPoint (.ppt)
File size: 1.09 MB
Date posted: 9/19/2016
Современное лечение ВИЧ: лечение многократно леченных пациентов с резистентно...hivlifeinfo
This document discusses management of HIV in heavily treatment-experienced patients with multiclass resistance and limited treatment options. It provides an overview of the problem, including that some older patients were treated early in the HIV epidemic with less potent regimens, resulting in resistance. Younger patients may have congenital HIV and been treated long-term. Assessment of virologic failure and resistance testing are important to select an effective new regimen. Current options for active drugs in these patients include maraviroc, ibalizumab, fostemsavir, and enfuvirtide, which have novel mechanisms of action. Adherence assessment is also critical to determine if the current regimen may still be effective if taken as prescribed.
This document discusses contemporary management of HIV with a focus on individualizing first-line antiretroviral therapy (ART). It provides an overview of recommended first-line ART regimens including integrase strand transfer inhibitors (INSTIs), discusses clinical trial data comparing different INSTI and protease inhibitor options, and considers factors in choosing among available single-tablet regimen options. It also addresses the potential roles of newer non-nucleoside reverse transcriptase inhibitors and tenofovir alafenamide versus tenofovir disoproxil fumarate in first-line ART.
Choosing Among Current Antiretroviral Regimens.The Relevance of Drug–Drug Int...hivlifeinfo
In this downloadable slideset, Jürgen K. Rockstroh, MD, reviews how selection of antiretroviral therapy is influenced by drug–drug interactions and differing antiretroviral genetic barriers to resistance.
Format: Microsoft PowerPoint (.ppt)
File size: 1.17 MB
Date posted: 11/4/2016
Incorporating New ART Options Into First-line and Switch Strategies for HIV C...hivlifeinfo
This document discusses several new HIV treatment regimens approved between 2017-2019, including three-drug fixed-dose combinations of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COBI/FTC/TAF). Clinical trials showed BIC/FTC/TAF and DOR/3TC/TDF were
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусной супрессией и ...hivlifeinfo
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусной супрессией и у пациентов с вирусологической неудачей. /Contemporary Management of HIV. Modifying Antiretroviral Therapy in Virologically Suppressed Patients and Those With Treatment Failure.2016
In this downloadable slideset, W. David Hardy, MD, and Program Director Eric S. Daar, MD review key data and optimal approaches for modifying ART in patients who are virologically suppressed or have experienced treatment failure.
Format: Microsoft PowerPoint (.ppt)
File size: 2.07 MB
Ключевые слайды по индивидуальному выбору АРТ / Key Slides on Individualized ...hivlifeinfo
Слайды с последними данные и рекомендациями по выбору АРТ, как для пациентов, ранее не получавших лечения, так и пациентов с вирусологической супрессией. Оценки разных вариантов лечения, индивидуализация АРТ для женщин детородного возраста и во время беременности, пациентов с опортунистическими инфекциями и новые данные об исследовательских стратегиях АРТ.
Слайдсет о новом в лечении ВИЧ.Key Slides on What’s Hot in HIV Treatment.2020 hivlifeinfo
Expert-authored slides on the latest issues relating to HIV care, featuring patient cases and considerations for optimal treatment approaches. Topics include integrating newer ARVs, individualizing ART for women of childbearing potential and during pregnancy, adverse events during ART, and anticipated roles of emerging ART strategies.
HIV Alert:ART Considerations for Aging Patients.2018hivlifeinfo
In this downloadable slideset, Eric S. Daar, MD, and David A. Wohl, MD, provide expert recommendations for older patients with HIV, both in terms of ART selection and general management.
Format: Microsoft PowerPoint (.ppt)
File size: 545 KB
Date posted: 2/12/2018
Managing cirrhotic HCV patients. Whom to treat, how to treat.2014Hivlife Info
Marc Bourlière, MD and Graham R. Foster, FRCP, PhD presented on managing cirrhotic HCV patients. They discussed which cirrhotic patients should be treated, how to treat them, and ensuring informed decision making. Patients with Child-Pugh A cirrhosis should be strongly advised to undergo therapy, while more advanced cases require careful consideration. New direct-acting antiviral regimens have increased sustained virologic response rates in cirrhotic patients, but they still face higher risks of side effects and disease progression if treatment is delayed. Physicians must fully inform patients of risks from both immediate treatment and deferring treatment to facilitate shared decision making.
Managing cirrhotic HCV patients. Whom to treat, how to treat.2014hivlifeinfo
Cirrhotic patients are the most in need of HCV treatment but also face challenges. Treatment is recommended for Child-Pugh A patients but more advanced cirrhosis requires caution. New drug combinations with direct-acting antivirals and pegylated interferon/ribavirin have increased sustained virologic response rates in cirrhotic patients, though they remain at risk for side effects and worsening liver function. Careful monitoring is needed when treating cirrhotic patients, especially those with significant risk factors like low platelet count or albumin level. Promising interferon-free regimens show high response rates even in prior treatment failures and may improve options for cirrhotic patients.
Современное лечение ВИЧ.Усилить или не усилить : преимущества и недостатки бу...hivlifeinfo
Современное лечение ВИЧ.Усилить или не усилить : преимущества и недостатки бустированных режимов АРТ / Contemporary Management of HIV.To Boost or Not to Boost-Advantages and Disadvantages of Boosted ART.2017
In this downloadable slideset, Eric S. Daar, MD, and Program Director Joseph J. Eron, Jr., MD, review advantages and disadvantages of boosted ART regimens for managing patients with HIV.
Format: Microsoft PowerPoint (.ppt)
File size: 514 KB
Date posted: 6/16/2017
Современное лечение ВИЧ.Обобщённые данные с конференции CROI 2020 / Contempor...hivlifeinfo
This document summarizes data presented at CROI 2020 on current and investigational antiretroviral therapies (ART) for HIV. Key findings include:
- A pooled analysis found the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was effective and well-tolerated in people over age 50 similar to younger patients.
- The switch to BIC/FTC/TAF was noninferior to remaining on baseline regimens even in people with baseline nucleoside reverse transcriptase inhibitor resistance.
- Through week 96, dolutegravir plus lamivudine was similarly effective
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014Hivlife Info
This document summarizes a presentation on new agents for treating hepatitis C virus (HCV) infection in patients coinfected with HIV. It discusses FDA-approved regimens containing simeprevir or sofosbuvir, dosing and administration, treatment guidelines from AASLD/IDSA, and clinical trial data on sofosbuvir and simeprevir in HIV/HCV coinfected patients, showing high sustained virologic response rates.
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супре...hivlifeinfo
This document discusses modifying antiretroviral therapy (ART) in virologically suppressed patients with HIV. It describes two phase 3 trials, ATLAS and FLAIR, that evaluated switching to long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) every 4 weeks in suppressed patients. Both trials found CAB/RPV to be noninferior to continued oral ART at 48 weeks. Common reasons to consider an ART switch include simplifying regimens or improving tolerability. Key factors that may increase risk of treatment failure with CAB/RPV include presence of rilpivirine resistance mutations at baseline and lower rilpivirine drug levels. The FDA
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
Современное лечение ВИЧ: новые парадигмы в АРТ / Contemporary Management of H...hivlifeinfo
Набор слайдов c рассмотрением важных вопросов об АРТ первого ряда, арв-препаратами пролонгированного действия и схемами АРТ с двумя препаратами, акцент в публикации на роль новых стратегий.
Expert Insights in Selecting a Switch Regimen for Virologically Suppressed HI...hivlifeinfo
Expert Insights in Selecting a Switch Regimen for Virologically Suppressed HIV-Infected Patients.2018
In this slideset, Babafemi Taiwo, MBBS, discusses expert approaches to selecting an HIV switch regimen in a series of cases studies involving HIV-infected patients with virologic suppression on their current ART regimen.
Format: Microsoft PowerPoint (.ppt)
File Size: 1.10 MB
HIV Alert :Updating Your Practice Based on New Guideline Recommendations.2016hivlifeinfo
In this downloadable slideset, Eric S. Daar, MD, and Paul E. Sax, MD, review recent updates to expert guideline recommendations for ART—including new initial therapy recommendations, revised guidance on switch strategies for virologically suppressed patients, and other key recommendation updates.
Format: Microsoft PowerPoint (.ppt)
File size: 1.09 MB
Date posted: 9/19/2016
Современное лечение ВИЧ: лечение многократно леченных пациентов с резистентно...hivlifeinfo
This document discusses management of HIV in heavily treatment-experienced patients with multiclass resistance and limited treatment options. It provides an overview of the problem, including that some older patients were treated early in the HIV epidemic with less potent regimens, resulting in resistance. Younger patients may have congenital HIV and been treated long-term. Assessment of virologic failure and resistance testing are important to select an effective new regimen. Current options for active drugs in these patients include maraviroc, ibalizumab, fostemsavir, and enfuvirtide, which have novel mechanisms of action. Adherence assessment is also critical to determine if the current regimen may still be effective if taken as prescribed.
This document discusses contemporary management of HIV with a focus on individualizing first-line antiretroviral therapy (ART). It provides an overview of recommended first-line ART regimens including integrase strand transfer inhibitors (INSTIs), discusses clinical trial data comparing different INSTI and protease inhibitor options, and considers factors in choosing among available single-tablet regimen options. It also addresses the potential roles of newer non-nucleoside reverse transcriptase inhibitors and tenofovir alafenamide versus tenofovir disoproxil fumarate in first-line ART.
Choosing Among Current Antiretroviral Regimens.The Relevance of Drug–Drug Int...hivlifeinfo
In this downloadable slideset, Jürgen K. Rockstroh, MD, reviews how selection of antiretroviral therapy is influenced by drug–drug interactions and differing antiretroviral genetic barriers to resistance.
Format: Microsoft PowerPoint (.ppt)
File size: 1.17 MB
Date posted: 11/4/2016
Incorporating New ART Options Into First-line and Switch Strategies for HIV C...hivlifeinfo
This document discusses several new HIV treatment regimens approved between 2017-2019, including three-drug fixed-dose combinations of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COBI/FTC/TAF). Clinical trials showed BIC/FTC/TAF and DOR/3TC/TDF were
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусной супрессией и ...hivlifeinfo
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусной супрессией и у пациентов с вирусологической неудачей. /Contemporary Management of HIV. Modifying Antiretroviral Therapy in Virologically Suppressed Patients and Those With Treatment Failure.2016
In this downloadable slideset, W. David Hardy, MD, and Program Director Eric S. Daar, MD review key data and optimal approaches for modifying ART in patients who are virologically suppressed or have experienced treatment failure.
Format: Microsoft PowerPoint (.ppt)
File size: 2.07 MB
Ключевые слайды по индивидуальному выбору АРТ / Key Slides on Individualized ...hivlifeinfo
Слайды с последними данные и рекомендациями по выбору АРТ, как для пациентов, ранее не получавших лечения, так и пациентов с вирусологической супрессией. Оценки разных вариантов лечения, индивидуализация АРТ для женщин детородного возраста и во время беременности, пациентов с опортунистическими инфекциями и новые данные об исследовательских стратегиях АРТ.
Слайдсет о новом в лечении ВИЧ.Key Slides on What’s Hot in HIV Treatment.2020 hivlifeinfo
Expert-authored slides on the latest issues relating to HIV care, featuring patient cases and considerations for optimal treatment approaches. Topics include integrating newer ARVs, individualizing ART for women of childbearing potential and during pregnancy, adverse events during ART, and anticipated roles of emerging ART strategies.
HIV Alert:ART Considerations for Aging Patients.2018hivlifeinfo
In this downloadable slideset, Eric S. Daar, MD, and David A. Wohl, MD, provide expert recommendations for older patients with HIV, both in terms of ART selection and general management.
Format: Microsoft PowerPoint (.ppt)
File size: 545 KB
Date posted: 2/12/2018
Managing cirrhotic HCV patients. Whom to treat, how to treat.2014Hivlife Info
Marc Bourlière, MD and Graham R. Foster, FRCP, PhD presented on managing cirrhotic HCV patients. They discussed which cirrhotic patients should be treated, how to treat them, and ensuring informed decision making. Patients with Child-Pugh A cirrhosis should be strongly advised to undergo therapy, while more advanced cases require careful consideration. New direct-acting antiviral regimens have increased sustained virologic response rates in cirrhotic patients, but they still face higher risks of side effects and disease progression if treatment is delayed. Physicians must fully inform patients of risks from both immediate treatment and deferring treatment to facilitate shared decision making.
Managing cirrhotic HCV patients. Whom to treat, how to treat.2014hivlifeinfo
Cirrhotic patients are the most in need of HCV treatment but also face challenges. Treatment is recommended for Child-Pugh A patients but more advanced cirrhosis requires caution. New drug combinations with direct-acting antivirals and pegylated interferon/ribavirin have increased sustained virologic response rates in cirrhotic patients, though they remain at risk for side effects and worsening liver function. Careful monitoring is needed when treating cirrhotic patients, especially those with significant risk factors like low platelet count or albumin level. Promising interferon-free regimens show high response rates even in prior treatment failures and may improve options for cirrhotic patients.
- An estimated 170 million people worldwide are infected with hepatitis C virus (HCV). New direct-acting antiviral (DAA) drugs such as sofosbuvir have improved sustained virologic response rates and reduced treatment duration and side effects compared to previous interferon-based regimens.
- Phase 2/3 clinical trials showed that 12 weeks of sofosbuvir plus peginterferon and ribavirin achieved high SVR rates of 88-99% in treatment-naive patients with genotypes 1, 4, 5, and 6 HCV. Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme.
New Data on Resistance to DAAs and Implications for Therapy.2015hivlifeinfo
This document provides an overview of a presentation on new data regarding resistance to direct-acting antivirals (DAAs) and implications for HCV therapy. It includes the faculty list and their disclosures, as well as slides summarizing recent studies on DAA resistance variants, their impact on treatment outcomes, and persistence after treatment failure. Key findings discussed are the role of NS3 Q80K testing prior to simeprevir + sofosbuvir in genotype 1a patients, effectiveness of DAA regimens against prior protease inhibitor resistance, and durability of NS5A resistance variants.
This document provides information about the 30th Annual New Treatments in Chronic Liver Disease conference taking place from March 20-22, 2015 in La Jolla, California. The conference will cover new medications and therapies for chronic liver diseases including hepatitis B and C, non-alcoholic fatty liver disease, and complications of end-stage liver disease. Over 13.5 hours of CME credits will be offered over the pre-conference on March 20th and main conference on March 21-22nd. Topics will include direct-acting antiviral regimens for HCV, new therapies for NASH, approaches towards curing HBV, and updates on treatments for conditions like PBC and PSC.
Thanks to Prof. Chavdar Pavlov, MD, PhD, MScD - Department Head of Therapy, Head of the Centre for Evidence-Based Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia for helping organizing this event in Moscow.
HCV Alerts- Rapid Response to Practice-Changing Advances From EASL 2015Hivlife Info
In this downloadable slideset, Mark S. Sulkowski, MD, discusses key practice-changing data from the 2015 liver disease meeting in Vienna.
Format: Microsoft PowerPoint (.ppt)
File size: 751 KB
HCV Alerts- Rapid Response to Practice-Changing Advances From EASL 2015hivlifeinfo
This document provides a summary of presentations from the EASL 2015 conference on advances in treating hepatitis C virus (HCV) infection. It discusses three key areas: managing HCV in patients with renal disease, the role of resistance testing in HCV retreatment, and advances in treating genotype 3 HCV infection. The document outlines several clinical trials presenting safety and efficacy results on using various direct-acting antiviral regimens to treat HCV in these special patient populations and clinical scenarios.
This document summarizes a presentation on the management of metastatic colorectal cancer (mCRC) in 2017. It discusses several key points:
1) Patient stratification is important in determining treatment approach for mCRC, taking into account factors like disease extent and symptoms.
2) A multidisciplinary team approach is mandatory for developing optimal treatment plans.
3) Assessment of predictive biomarkers like RAS mutations helps determine which first-line treatments may be most effective.
4) Tumor location (right vs left-sided colon cancer) can impact treatment outcomes and response to certain drugs like anti-EGFR therapies.
5) Multiple clinical trials over time have led to improved survival outcomes and more
Hepatitis (C) Story …. Past & Present & future
Most Recant Updating Guidelines by ASSLD & FDA
RAVS &How to deal with It ----12/7/2016.....
((Residents Lectures))
Aidsrounds121412morris 121214115641-phpapp01Lucas Brown
The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians and researchers to provide the most current research, clinical practices, and trends in HIV and other infectious diseases. The slides from an AIDS Clinical Rounds presentation are intended for educational purposes of the audience and may not be used without the presenter's permission. The presentation provides an update on PrEP (pre-exposure prophylaxis) for HIV, including data on efficacy from recent studies, pharmacology, adverse events, and guidance for its use.
Crimson Publishers: Interferon-Free Therapy for Hepatits C in Brazil and Sust...CrimsonGastroenterology
Introduction: Hepatitis C has been treated with interferon and ribavirin for over a decade with described global sustained virological response rates of 33% to 56%. Direct acting antiviral drugs available since 2013 in USA and 2015 in Brazil are changing this reality.
Purpose: Analyze the real-life efficacy and safety of interferon-free therapy.
Methods: Repot six cases of different treatments guided by north-american and european guildelines.
Results: Every reported patient achieved sustained virological response. The only adverse event was anemia in one patient.
Conclusion: Direct-acting antiviral drugs will dramatically change the population which can be treated and increase sustained virological response rates.
Новые данные с конференции по ВИЧ-инфекции CROI 2017/Clinical Impact of New D...hivlifeinfo
Clinical Impact of New Data From CROI 2017
Expert faculty members Joel E. Gallant, MD, MPH, and Charles B. Hicks, MD, summarize key studies from this important annual conference.
Format: Microsoft PowerPoint (.ppt)
File size: 1.25 MB
Date posted: 3/3/2017
CẬP NHẬT ĐIỀU TRỊ VIÊM GAN VIRUS C MẠN NĂM 2017 bientap2
The document discusses updates to treatment of chronic hepatitis C virus (HCV) infection in 2017. It notes that approximately 200 million people worldwide are infected with HCV, with genotype 1 being the most common globally. New direct-acting antiviral (DAA) drugs have greatly improved treatment success rates for HCV compared to previous interferon-based regimens. Treatment is now recommended for all patients with chronic HCV infection except those with very short life expectancies. Various DAA combinations can achieve sustained virologic response rates of over 90% for genotypes 1-6, including for patients with advanced fibrosis or cirrhosis. Ongoing challenges include optimizing treatment for all genotypes, managing side effects, monitoring after treatment, and ensuring
CẬP NHẬT ĐIỀU TRỊ VIÊM GAN VIRUT MAN NĂM 2017Great Doctor
The document discusses updates to treatment of chronic hepatitis C virus (HCV) infection in 2017. It notes that approximately 200 million people worldwide are infected with HCV, with genotype 1 being the most common globally. New direct-acting antiviral (DAA) drugs have greatly improved treatment success rates for HCV compared to previous interferon-based regimens. Treatment is now recommended for all patients with chronic HCV infection except those with very short life expectancies. Various DAA combinations can achieve sustained virologic response rates of over 90% for genotypes 1-6, including for patients with advanced fibrosis or cirrhosis. Ongoing challenges include optimizing treatment for all genotypes, managing side effects, monitoring after treatment, and ensuring
NAFLD Patients have Limited Access to GLP1 Agonists and SGLT2 Inhibitors: NHA...JohnJulie1
This study analyzed medication use among patients with NAFLD and/or advanced fibrosis using NHANES 2017-2018 data. The following key points are summarized:
1. Patients with NAFLD or advanced fibrosis had higher rates of polypharmacy, with more medications and medication classes compared to those without these conditions.
2. While medication usage indicated higher risk of cardiovascular and metabolic issues associated with NAFLD, usage of GLP1 agonists and SGLT2 inhibitors was low among diabetics regardless of NAFLD status.
3. Diabetics with advanced fibrosis had fewer medications on average than those without advanced fibrosis, possibly due to disease progression effects, though access to beneficial therapies like G
Sunitinib for the pancreatic neuroendocrine tumors, Moh'd sharshirMoh'd sharshir
1) Pancreatic neuroendocrine tumors are rare tumors that arise in the pancreas and often spread to the liver. Surgery is the primary treatment but many tumors are inoperable or metastasize.
2) The study examined using the drug sunitinib to treat advanced pancreatic neuroendocrine tumors, as these tumors rely on angiogenesis facilitated by growth factors like VEGF.
3) In a phase 3 clinical trial, 171 patients were randomized to receive either sunitinib or a placebo pill daily. Sunitinib was shown to significantly extend progression-free survival compared to the placebo. Overall survival and response rates were also improved with sunitinib treatment.
This document summarizes a presentation on hepatitis C virus (HCV) natural history and therapeutics by Dr. Alnoor Ramji. It discusses how HCV has a slowly progressive course that can lead to cirrhosis and complications like liver cancer. New all-oral drug regimens are highly effective, achieving viral eradication rates of 70-98%, and viral eradication improves mortality outcomes. The presentation reviews HCV genotypes and disease progression, outlines improvements in treatment efficacy over time, and discusses side effects and outcomes of newer protease inhibitor and nucleotide/nucleoside analog regimens.
Similar to Shaping the Future.Clinicians and Faculty Define - Strategies for the Next Era of HCV Therapy.2014 (20)
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Clinical Impact of New Data From AIDS 2020hivlifeinfo
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Гиперлипопротеидемия(а) как опасное генетически обусловленное нарушение липид...hivlifeinfo
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This document summarizes an expert panel discussion on innovative antiretroviral therapy (ART) paradigms. The panel discussed whether positive results from two-drug and long-acting injectable regimens in clinical trials will translate to long-term efficacy and safety. They also considered the potential risks of resistance emerging with two-drug regimens and the impact of missed doses with long-acting injectables. The panel agreed that maintaining cold storage requirements for long-acting injectables may pose challenges for implementation in low- and middle-income countries but that qualitative research found patients highly satisfied with the convenience of long-acting ART.
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Shaping the Future.Clinicians and Faculty Define - Strategies for the Next Era of HCV Therapy.2014
1. Shaping the Future: Clinicians and
Faculty Define Strategies for the
Next Era of HCV Therapy
This program is supported by educational grants from
2. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Program Director
Mark S. Sulkowski, MD
Professor of Medicine
Medical Director, Viral Hepatitis Center
Divisions of Infectious Diseases and Gastroenterology/Hepatology
Johns Hopkins University School of Medicine
Baltimore, Maryland
3. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Faculty
Jordan J. Feld, MD, MPH
Assistant Professor of Medicine
University of Toronto
Hepatologist
Toronto Western Hospital Liver Centre
McLaughlin-Rotman Centre for Global
Health
Toronto, Ontario, Canada
Graham R. Foster, FRCP, PhD
Professor of Hepatology
The Liver Unit
Consultant Hepatologist
Queen Marys University of London
London, United Kingdom
Michael W. Fried, MD
Professor of Medicine
Director, UNC Liver Center
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Alessandra Mangia, MD
Liver Unit Hospital ‘Casa Sollievo della
Sofferenza’
Istituto di Ricovero e Cura a Carattere
Scientifico
San Giovanni Rotondo, Italy
Fred Poordad, MD
Vice President, Academic and Clinical
Affairs
The Texas Liver Institute
Professor of Medicine
University of Texas Health Science Center
San Antonio, Texas
Stefan Zeuzem, MD
Professor of Medicine
Chief, Department of Medicine I
JW Goethe University Hospital
Frankfurt, Germany
4. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
New Standard of Care for HCV in
2013/2014
Standard
Interferon
Interferon +
Ribavirin
Peginterferon/
Ribavirin
1991 1998 2001
2005
Boceprevir or
Telaprevir +
P/R
GT1
GT2/3
2011 2013
2013
Simeprevir or
Sofosbuvir +
P/R
Sofosbuvir +
Ribavirin
5. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Key Questions That Define the Future of
Hepatitis C Virus Therapy
How do we determine the best regimen for genotype 1 going forward?
Jordan J. Feld, MD, MPH
Why does genotype 3 do poorly and how can we do better?
Stefan Zeuzem, MD
Is one-size-fits-all treatment a possibility and how would that change
management?
Alessandra Mangia, MD
How will we manage patients who fail direct-acting antiviral therapies?
Graham R. Foster, FRCP, PhD
Why do cirrhotics do poorly and how can we do better?
Fred Poordad, MD
How will high-risk patients be managed going forward?
Michael W. Fried, MD
6. Jordan J. Feld, MD, MPH
Assistant Professor of Medicine
University of Toronto
Hepatologist
Toronto Western Hospital
Liver Centre
McLaughlin-Rotman Centre for Global
Health
Toronto, Ontario, Canada
How Do We Determine the Best
Regimen for Genotype 1 Going
Forward?
7. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Summary of New Agents for GT1 in 2013
Sofosbuvir + P/R
– Sofosbuvir is oral, once daily
– 12 wks with P/R
– SVR rate 89% in naives
– Low impact of baseline factors
Simeprevir + P/R
– Simeprevir is oral, once daily
– 12 wks with P/R + 12-36 wks with P/R
– SVR rate 80% in naives
– Q80K testing will be needed in GT 1a
Baseline Factor SVR12, % (n/N)
Black
Non-Black
86 (43/50)
90 (218/242)
Genotype 1a
Genotype 1b
92 (206/225)
82 (54/66)
Cirrhosis*
No cirrhosis*
80 (43/54)
92 (252/273)
*Represents GT 1/4/5/6.
Sofosbuvir FDA hearing. October 25, 2013. Simeprevir FDA hearing. October 24, 2013.
Baseline Factor SVR12, % (n/N)
Black
Non-Black
67 (29/43)
81 (378/464)
GT1a with Q80K
GT 1a, no Q80K
GT 1b
58 (49/84)
84 (138/165)
85 (228/267)
F3-F4*
F0-F2*
68 (89/130)
84 (317/378)
8. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Priorities
SVR trumps all
But SVR is a necessity—assuming SVR > 90%, what is next?
Considerations
– Several new P/R-based regimens completing phase III
– Faldaprevir + P/R
– Daclatasvir + P/R
– But with 89% SVR with 12-wk SOF + P/R, will there be a clinical role for
longer-duration P/R-based regimens?
– An all-oral future for GT1: multiple studies of 12- to 16-wk regimens
9. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Over-
treatment
of some
Tailored
regimen
for each
population
Priorities
Cost
Fewest
drugs
Shortest
duration
Simplicity
One size
fits all
10. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
2/12
One Size Fits All or Simpler Regimen for
Genotype 1b Only?
Genotype 1, naive
10% had cirrhosis
Dufour J-F, et al. AASLD 2013. Abstract 1102.
16-Wk Regimen: Faldaprevir (PI) 120 mg QD
+ Deleobuvir (NNI) 600 mg BID + RBV
(N = 32)
Simple regimen for genotype 1b only?
What if it were very cheap?
EOT SVR12
UndetectableHCV
RNA(IU/mL)
100
80
60
40
20
0
58
100
17
95
7/12 20/20 19/20
Genotype 1a,
IL28B CC
Genotype 1b
11. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
One Size Fits All or Simpler Regimen for
GT1b? Various Ways to Look at the Same Data
82
0
20
40
60
80
100
SVR12(%)
100 100 100 100 100
79
100
29 12
85
100
52 27
83
96
52 25
96 100
54 25
81
100
26 18
89
100
28 17
Observed data
(above bar)
ITT (within bar)
n =
81
98
8888
100
89
1a 1b 1a 1b 1a 1b 1a 1b 1a 1b 1a 1b
ABT-450
ABT-333
RBV
ABT-450
ABT-267
RBV
ABT-450
ABT-267
ABT-333
ABT-450
ABT-267
ABT-333
RBV
ABT-450
ABT-267
RBV
ABT-450
ABT-267
ABT-333
RBV
Treatment-Naive Patients Null Responders
Kowdley KV, et al. AASLD 2012. Abstract LB-1.
ABT-450/RTV (PI) ± ABT-333 (NNI) +
ABT-267 (NS5A) ± RBV x 12 Wks
One size fits all OR “simpler regimen” for GT1b?
12. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
What Is the Role of Ribavirin for
Genotype 1 Going Forward?
Still an enigma
Prevents/delays resistance
– Important for genotype 1a
– Important with NNI, PI, and NS5A
– Not relevant with NI-based combination
Reduces relapse
– May be relevant with shorter durations
– Limited data to date but does not look critical for most
NI-based combination regimens
13. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Same Duration for All or Shorter for Naive,
Longer for Previous Failures?
12 wks for all or 8 for naive and 12 for failures?
What about RBV? A third DAA for 6 wks?
SVR12(%)
0
20
40
60
80
100
19/
20
SOF
LDV
SOF
LDV
RBV
SOF
LDV
95
100
21/
21
95
18/
19
95
SOF
LDV
100
18/
19
21/
21
8 Wks 12 Wks 12 Wks
SOF
LDV
RBV
Naive
PI failure
n/N =
Lawitz E, et al. AASLD 2013. Abstract 215.
15. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Research continues for GT1 HCV
– More tailored approach in the near future
– Longer duration or additional agents for difficult-to-treat
populations?
One-size-fits-all approach ideal for inexperienced
providers
Rising demand for treatment anticipated
– Increased screening
– Availability of IFN-free regimens
16. Stefan Zeuzem, MD
Professor of Medicine
Chief, Department of Medicine
JW Goethe University Hospital
Frankfurt, Germany
Why Does Genotype 3 Do Poorly
and How Can We Do Better?
17. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Standard Treatment for GT2/3 HCV
Before treatment
(HCV RNA
quantification)
16 wks
therapy
HCV RNA
< 12-15
IU/mL
Pre-tx
< 8 x 105
IU/mL*
48 wks
therapy‡
HCV RNA
≥ 2 log
decline†
Wk 4
HCV RNA quantification
Wk 12
HCV RNA
quantification
24 wks
therapy
HCV RNA
< 12-15
IU/mL
*No treatment shortening in patients with advanced fibrosis, cirrhosis, metabolic syndrome, insulin resistance, HIV/HCV
coinfection, etc. No data for patients with persistently normal ALT levels. †
Detectable HCV RNA at Wk 24: discontinuation
of treatment.‡
Treatment duration of 36, 48, 72 wks in slow responders is currently investigated in prospective trials.
Tx
discontinued
< 2 log decline
EASL Practice Guidelines.
18. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
FISSION: Poorer Response to SOF/RBV in
GT3 vs GT2 Naives, Especially Cirrhotics
Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
SVR12(%)
All Patients Patients With Cirrhosis
n/N =
10/
11
13/
38
8/
13
11/
37
100
80
60
40
20
0
97
56
78
63
91
34
62
30
68/
70
52/
67
102/
183
110/
176
GT2 GT3
SOF/RBV 12 Wks
PegIFN/RBV 24 Wks
GT2 GT3
19. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
FUSION: Impact of Cirrhosis and Duration
on SVR Rates
Jacobson IM, et al. N Engl J Med. 2013;368:1867-1877.
6/10 5/26
SVR12(%)
25/26 7/923/23 14/38 14/2325/40
No Cirrhosis
Sofosbuvir + RBV 12 wks Sofosbuvir + RBV 16 wks
No CirrhosisCirrhosis Cirrhosis
Genotype 2 Genotype 3
19
6163
37
n/N =
100
80
60
40
20
0
96
100
60
78
100
80
60
40
20
0
SVR12(%)
n/N =
20. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Wk 0 Wk 24 SVR4,
SVR12,
SVR24
Placebo*
(n = 85)
Sofosbuvir + Ribavirin
(n = 84)*
*Protocol amended to eliminate placebo arm. 12-wk arm predominantly GT2 patients
(N = 73); 11 GT3 patients completed 12 wks of SOF + RBV prior to amendment to extend
treatment duration.
Zeuzem S, et al. AASLD 2013. Abstract 1085.
VALENCE: Evaluating Impact of Duration
on SVR With SOF/RBV
Wk 12
Tx-naive or
-experienced
GT2 or GT3 pts
21. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Overall Treatment Naive Treatment Experienced
SVR4(%)
n/N =
2/
2
30/
33
12/
13
87/
100
100
80
60
40
20
0
93
97
85
94
100
9192
87
68/
73
212/
250
29/
30
86/
92
No Cirrhosis Cirrhosis
7/
8
27/
45
88
60
No Cirrhosis CirrhosisOverall
12 wks of SOF + RBV in GT2
24 wks of SOF + RBV in GT3
Zeuzem S, et al. AASLD 2013. Abstract 1085. Jacobson IM, et al. N Engl J Med. 2013;368:1867-1877.
Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
VALENCE Efficacy Summary: SVR12
Phase III GT3 SVR12 data summary:
– TN noncirrhotics, 12 wks: 61% (FISSION)
– TN cirrhotics, 12 wks: 34% (FISSION)
– TE noncirrhotics, 16 wks: 63% (FUSION)
– TE cirrhotics, 16 wks: 61% (FUSION)
22. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Most GT3 patients will be able to be treated with 24 wks of
SOF/RBV
GT3, treatment-experienced, cirrhotic patients most
challenging group to treat with all-oral regimens
– Experts recommend 12 wks of SOF + pegIFN/RBV in short
term
23. Alessandra Mangia, MD
Liver Unit Hospital 'Casa Sollievo della
Sofferenza'
Istituto di Ricovero e Cura a Carattere
Scientifico
San Giovanni Rotondo, Italy
Is One-Size-Fits-All Treatment a
Possibility and How Would That
Change Management?
24. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
How Far Are We?
One Size . . . . . . Fits All?
Same treatment regardless of
fibrosis level, previous treatment
experience, or HCV genotype?
25. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
AVIATOR: Less Impact of Traditional
Negative Predictors on SVR Rates
Comparable high SVR rates among 247 patients administered 12 or 24 wks of
treatment
All enrolled patients were noncirrhotic
Kowdley KV, et al. EASL 2013. Abstract 3.
Treatment Naive Null Responders
100
80
60
40
20
0
M
aleFem
ale
1a
1b
≥
7log
F0-F1
<
7
log
F2-F3Non-CC
CC
SVR24(%)
SVR24(%)
n =
92 94 91
98
89
94 94 91
95
89
78 81 108 50 35 124 113 42 115 44
100
80
60
40
20
0
M
aleFem
ale
1a
1b
≥
7
log
F0-F1
<
7
log
F2-F3Non-CC
CC
n =
93
97 93 97
91
96 95 93 94
100
55 33 55 33 22 66 41 45 85 3
26. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
GT1 HCV Tx Naive: SVR Rates With
12 Wks of IFN-Free Tx in Phase II Studies
Few or no cirrhotic patients included in above studies
Corresponding rates for 24-wk regimens showed SVR12/24 of 52% (QUANTUM[1]
), 95%
to 100% (AI-444040[6]
), 93% (AVIATOR[5]
), 94% (A1443-014[8]
)
1. Lalezari LP, et al. EASL 2013. Abstract 845. 2. Gane E, et al. EASL 2013. Abstract 14. 3. Lawitz E, et al. AASLD 2013.
Abstract 215. 4. Sulkowski MS, et al. AASLD 2012. Abstract LB-2. 5. Kowdley K, et al. EASL 2013. Abstract 3. 6. Everson G,
et al. AASLD 2013. Abstract LB-1. 7. Lawitz E, et al. AASLD 2013. Abstract 76. 8. Sulkowski M, et al. EASL 2013. Abstract
1423.
Regimen N Study SVR 4/12, %
SOF (NS5B) + RBV 25 QUANTUM[1]
56
SOF (NS5B) + RBV 25 ELECTRON[2]
84
SOF (NS5B) + LDV (NS5A) 19 LONESTAR[3]
95
SOF (NS5B) + DCV (NS5A) ± RBV 82 AI-444040[4]
98-100
ABT-450 (PI) + ABT-267 (NS5A) + ABT-333
(NS5B) ± RBV
158 AVIATOR[5]
94
DCV (NS5A) + ASV (PI) + BMS-791325 (NS5B) 161 A1443-014[6]
92
MK-5172 (PI) + MK-8742 (NS5A) ± RBV 65 C-WORTHY[7]
96-100
27. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Phase III Studies of Sofosbuvir (Nuc) +
Ledipasvir (NS5A) ± RBV in GT1 HCV
ION-1*: GT1 Tx-Naive Pts
(16% Cirrhotic): SOF/LDV
FDC ± RBV for 12 Wks
Press release. These data are available in press release format only, have not been peer reviewed, may be incomplete,
and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.
*24-wk arms not yet reported.
ION-3: GT1 Tx-Naive Pts:
SOF/LDV FDC ± RBV
for 8 or 12 Wks
SOF/LDV FDC
SOF/LDV FDC +
RBV
n/N =
209/
214
211/
217
SVR12(%)
12 Wks
98 97100
90
60
40
20
0
8 Wks 12 Wks
202/
215
206/
216
201/
216
94 93 95
28. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
12-Wk Treatment in Previous Null
Responders?
ABT-450/RTV + ABT-267 +
ABT-333 + RBV
12 Wks
SVR12(%)
Naive
n/N =
42/
45
F0-F2 fibrosis
SVR4/12(%)
n/N =
SMV + SOF
+ RBV
12 Wks
SMV + SOF
12 Wks
*No F4
COSMOS[1,2]
Caveat: small numbers,
few patients with cirrhosis
1. Jacobson IM, et al. AASLD 2013. Abstract LB-3. 2. Lawitz E, et al. CROI 2013. Abstract 155LB.
3. Kowdley K, et al. EASL 2013. Abstract 3.
26/
27
13/
14
96 93
76/
79
14/
15
7/
7
93
100
F3/4 fibrosis
96 93
AVIATOR[3]
100
80
60
40
20
0
Null*
100
80
60
40
20
0
29. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
SAPPHIRE Phase III Studies: PI Backbone
+ 2 Other DAAs
SAPPHIRE-1: GT1 Tx-Naive
Noncirrhotic Pts:
ABT-450/RTV/ABT-267 FDC
+ ABT-333 + RBV for 12 Wks
Press release. These data are available in press release format only, have not been peer reviewed, may be incomplete,
and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.
n/N =
455/
473
307/
322
148/
151
SAPPHIRE-2: GT1 Tx-Experienced
Noncirrhotic Pts (49% Null Responders):
ABT-450/RTV/ABT-267 FDC
+ ABT-333 + RBV for 12 Wks
100
80
60
40
20
0
SVR12(%)
96 95 98
Overall GT1a GT1b
n/N =
286/
297
166/
173
119/
123
100
80
60
40
20
0
SVR12(%)
96 96 97
Overall GT1a GT1b
30. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
SOF-Based IFN-Free DAA Treatment in
GT1 Treatment-Experienced Patients
SOF + LDV + RBV x 12 wks
(prior null, noncirrhotic)
100
80
60
40
20
0
SVR4/12(%)
100[1]
2 DAAs + RBV
SOF + LDV x 12 wks (prior
PI failures, 50% cirrhotic)
2 DAAs, No RBV
7/10
70[2]
9/9
100[2]
SOF + LDV + RBV x 12 wks
(TE with cirrhosis)
SOF + LDV x 12 wks
(TE with cirrhosis)
95[3]
1. Gane EJ, et al. CROI 2013. Abstract 41LB. 2. Gane EJ, et al. AASLD 2013. Abstract 73. 3. Lawitz E, et
al. AASLD 2013. Abstract 215.
18/199/9n/N =
31. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Phase III Studies of Sofosbuvir (Nuc) +
Ledipasvir (NS5A) ± RBV in GT1 HCV
Press release. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we
await presentation or publication in a peer-reviewed format before conclusions should be made from these data.
SOF/LDV FDC SOF/LDV FDC + RBV
ION-2: GT1 Treatment-Experienced Pts (20% Cirrhotic):
SOF/LDV FDC ± RBV for 12 or 24 Wks
n/N =
SVR12(%)
100
90
60
40
20
0
12 Wks 24 Wks
102/
109
107/
111
108/
109
110/
111
94 96 99 99
32. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Challenging Patient Groups
Patients with cirrhosis
HCV genotype 3 infection
Patients nonresponsive to DAA regimens
HIV coinfection
33. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Future role for specialists in HCV
– Treating more complex cases
– Determining indication for starting treatment
– Surveillance of cirrhotic patients following successful therapy
34. Graham R. Foster, FRCP, PhD
Professor of Hepatology
The Liver Unit
Consultant Hepatologist
Queen Marys University of London
London, United Kingdom
How Will We Manage Patients Who
Fail Direct-Acting Antiviral
Therapies?
35. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
DAA Failures: The Principles
In other viral infections, “failure” can be resolved by
complementary drugs
– eg, in HBV, lamivudine failures respond to adefovir or
tenofovir
Will the same hold true for HCV?
36. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
High SVR Rates With 24 Wks of All-Oral
Therapy in GT1 Patients With PI Failure
Sulkowski MS, et al. EASL 2013. Abstract 1417.
*1 patient in daclatasvir/sofosbuvir/RBV arm had missing data at Wk 12 posttreatment; this patient had
undetectable HCV RNA at Wk 4 and Wk 24 posttreatment.
SVR4 SVR12
24 wks of daclatasvir
+ sofosbuvir
24 wks of daclatasvir
+ sofosbuvir + RBV
100 100 100
95*100
80
60
40
20
0
Patients(%)
n/N =
21/
21
20/
20
21/
21
19/
20
37. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
LONESTAR: High SVR Rates With 12 Wks
of Therapy in GT1 Patients With PI Failure
Lawitz E, et al. AASLD 2013. Abstract 215.
12 wks of SOF/LDV FDC
12 wks of SOF/LDV FDC + RBV
95
100
100
80
60
40
20
0
SVR12(%)
n/N =
18/
19
21/
21
38. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Complementary Regimens:
Drug Classes for the Future
Nucleotide polymerase inhibitors (eg, sofosbuvir)
NS5A inhibitors (eg, daclatasvir, ledipasvir)
Protease inhibitors (eg, simeprevir, faldaprevir)
Non-nucleotide polymerase inhibitors (3 different classes)
Host-targeting drugs (cyclophilins, microRNAs RIG-I
activators)
Which will work best together?
39. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Second-line therapy and beyond
– New challenges with increased treatment options
– Continued treatment failures anticipated with more difficult-
to-treat populations
Managing treatment failures
– Determine cause
– Risk factors – modifiable?
– Adherence with all-oral regimens
– Patient education and adherence management key
40. Fred Poordad, MD
Vice President
Academic and Clinical Affairs
The Texas Liver Institute
Professor of Medicine
University of Texas Health Science Center
San Antonio, Texas
Why Do Cirrhotics Do Poorly and
How Can We Do Better?
41. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
CUPIC: Telaprevir or Boceprevir + P/R
in GT1 Treatment-Experienced Cirrhotics
Fontaine H, et al. EASL 2013. Abstract 60. Hezode C, et al. J Hepatol. 2013;59:434-441.
n/N =
118/
295
79/
190
61/
116
43/
85
43/
135
32/
80
8/
28 1/9
100
80
60
40
20
0
SVR12(%)
Overall Relapsers PRs NRs
40 41
53 51
32
40
29
11
Telaprevir + P/R
Boceprevir + P/R
Risk of Death or Severe
Complications, % (n/N)
Platelet Count
> 100,000 cells/mm3
Platelet Count
≤ 100,000 cells/mm3
Albumin ≥ 35 g/L 3.4 (10/298) 4.3 (3/69)
Albumin < 35 g/L 7.1 (2/28) 44.1 (15/34)
42. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Impact of Cirrhosis on SVR12 With
Next-Generation PI + P/R
Jacobson I, et al. EASL 2013. Abstract 1425. Ferenci P, et al. EASL 2013. Abstract 1416.
18/
31n/N =
5/
17
188/
229
60/
113
82
53
58
29
Simeprevir + P/R
P/R
100
80
60
40
20
0
SVR12(%)
No Cirrhosis Cirrhosis
QUEST-1:
Simeprevir + P/R
Treatment-Naive GT1
172/
212
30/
45
9/
16
100
80
60
40
20
0
81
67
56
< F3 ≥ F3 F4
STARTVerso1:
Faldaprevir + P/R
Treatment-Naive GT1
Faldaprevir + P/R
43. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Impact of Cirrhosis on SVR12 With
Sofosbuvir-Based Therapy in Tx-Naive Pts
Lawitz E, et al. EASL 2013. Abstract 1411. Zeuzem S, et al. AASLD 2013. Abstract 1085.
SVR12(%)
92
80
252/
273 43/54
NEUTRINO:
12 Wks of SOF +
P/R
GT1/4/5/6
Genotype 2 Genotype 3
58/59 10/11 89/145 13/38
100
80
60
40
20
0
n/N =
98
91
61
34
FISSION:
12 Wks of SOF + RBV
GT2/3
CirrhoticNoncirrhotic
94
86/92 12/13
92
VALENCE:
24 Wks of SOF +
RBV
GT3
Genotype 1/4/5/6 Genotype 3
100
80
60
40
20
0
100
80
60
40
20
0
44. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
100
80
60
40
20
0
37
63
87
19
61 60
No Cirrhosis Cirrhosis
Impact of Duration, Addition of PegIFN on
Efficacy of SOF in Tx-Experienced GT2/3
FUSION: 12 wks of SOF/RBV
FUSION: 16 wks of SOF/RBV
VALENCE: 24 wks of SOF/RBV
LONESTAR-2:
12 Wks of SOF + PegIFN/RBV
Sofosbuvir FDA hearing. October 25, 2013. Lawitz E, et al. AASLD 2013.
SVR12(%)
14/
38
25/
40
87/
100
5/
26
14/
23
27/
45
Genotype 3
100
80
60
40
20
0
96 93
100
83 83 83
Genotype 2 Genotype 3
SVR12(%)
Overall Cirrhotic Noncirrhotic
n/N =
22/
23
13/
14
9/
9
20/
24
10/
12
10/
12
45. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Efficacy of IFN-Free DAA Combinations in
Tx-Naive and Tx-Experienced Cirrhotics
COSMOS:
12-Wk Regimens in GT1 HCV Cirrhotic
Tx-Naive or Previous Null Responders
SVR4/12(%)
Jacobson IM, et al. AASLD 2013. Abstract LB-3. Lawitz E, et al. AASLD 2013. Abstract 215. Everson GT,
et al. AASLD 2013. Abstract LB-1.
LONESTAR:
12-Wk Regimens in GT1 HCV
PI Failures (55% Cirrhotic)
AI443-014:
12-Wk Regimen in GT1
Tx-Naive Cirrhotics
100
80
60
40
20
0
91
100
10/11 7/7
Simeprevir + sofosbuvir + RBV
Simeprevir + sofosbuvir
100
80
60
40
20
0
18/19 21/21
95
100
Sofosbuvir/ledipasvir
Sofosbuvir/ledipasvir + RBV
100
80
60
40
20
0
87
Daclatasvir + asunaprevir
+ BMS-791325
13/15n/N =
46. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Eradication of HCV optimal before progression to cirrhosis
Poorer response of cirrhotic patients likely multifactorial
– Poor prior IFN response and GT3 most challenging
Treatment approaches
– GT3 experienced, cirrhotic: 12 wks of SOF + pegIFN/RBV
– GT3 naive, cirrhotic: 24 wks of SOF + RBV
Further improvements anticipated with DAA combinations
47. Michael W. Fried, MD
Professor of Medicine
Director, UNC Liver Center
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
How Will High-Risk Patients Be
Managed Going Forward?
48. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Goals of Antiviral Therapy
Decompensated cirrhosis
– Eradicate HCV to prevent further deterioration
– Eradicate HCV to prevent reinfection of graft
– Improve hepatic functional status
– Delay or obviate the need for transplantation
Posttransplantation
– Treat acute complications of HCV reinfection
– Prevent/arrest progression to cirrhosis
– Improve morbidity and mortality
– Liver related
– Extrahepatic effects on cardiovascular disease
49. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
HCV Management Issues Unique to
Pre- and Posttransplantation Patients
Pretransplantation
– Intolerance to peginterferon regimens
– Impaired hepatic metabolism
– Renal insufficiency
Posttransplantation
– High HCV RNA/impact of immunosuppression
– Fibrosing cholestatic hepatitis
– Drug–drug interactions
– Renal insufficiency
– Other medical comorbidities
50. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
PegIFN/RBV Before Transplantation to
Minimize HCV Recurrence Post-LT
Everson GT, et al. Hepatology. 2013;57:1752-1762.
P = .6011
TreatedLTPatients(%)
100
80
60
40
20
0
Overall
(n = 44)
GT1/4/6
(n = 23)
GT2/3
(n = 44)
59
25
52
22
67
29
HCV RNA negative at LT
HCV RNA negative 12 wks of post-LT
51. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Characteristic SOF + RBV
(N = 61)
Median age, yrs (range) 59 (46-73)
HCV genotype, %
1a 39
1b 34
2 13
3a 12
4 2
Non-CC IL28B genotype, % 78
CTP score, %
5-7 96
8 5
Previous HCV treatment, % 75
Pretransplant Sofosbuvir + RBV to
Prevent Posttransplant HCV Recurrence
Study 025: single-arm, open-label,
phase II study from 16 LT sites
– Listed for LT due to HCC meeting
Milan criteria
– MELD exception for HCC
– CTP score ≤ 7
Excluded decompensated cirrhosis,
renal impairment, living donor LT
Pre-LT therapy: SOF 400 mg/day +
RBV 1000-1200 mg/day for 48 wks
or until time of LT
– Post-LT immunosuppression:
≥ 12 wks of tacrolimus +
prednisone + MMF
Curry MP, et al. AASLD 2013. Abstract 213.
52. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Duration of Undetectable HCV RNA Before
Transplant Predicted Lack of Recurrence
64% of pts HCV RNA negative 12 wks
post-LT (93% at LT)
Continuous days TND pre-LT only
factor predicting HCV recurrence in
multivariate analysis
– Only 1/24 pts with > 30 days TND
experienced recurrence
Curry MP, et al. AASLD 2013. Abstract 213.
3300 30 60 90 120 150 180 210 240 270 300
Days With HCV RNA Continuously TND Prior to LT
> 30 days TND
No recurrence (n = 28)
Recurrence (n = 10)
Median days TND (P < .001)
No recurrence: 95
Recurrence: 5.5
53. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
CRUSH C: PI + PegIFN/RBV in Liver
Transplantation Recipients
112 patients: 30 were F4 or FCH
Treatment: TVR 88% or BOC 12%
– P/R lead-in 96%
Verna EC, et al. EASL 2013. Abstract 23.
HCVRNA<LOD(%)
100
80
60
40
20
0
EOTR SVR4
67 65
n = 43
Adverse Effect All Patients
(N = 112)
AE requiring treatment d/c, % 11
Dose reduction, %
PegIFN/RBV 34/80
Transfusion, % 46
Erythropoietin, % 79
G-CSF 41
Hospitalization, %* 21
Renal function
Cr increase > 0.5 mg/dL, %
Max ↑ in Cr, mg/dL (range)
34
0.4 (0-2.5)
Rejection, %†
4
Death, % 6
*Significantly differed between groups (P = .02).
†
Any treated rejection during or after TT.
54. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Daclatasvir 60 mg/day +
Sofosbuvir 400 mg/day
Case Report: Sofosbuvir + Daclatasvir in
Post-LT Fibrosing Cholestatic Hepatitis
Fontana RJ, et al. Am J Transplant. 2013;13:1601-1605.
8
7
6
5
4
3
2
1
0
LogHCVRNA(IU/mL)
Treatment Wk
400
350
300
250
200
150
100
50
0
ALT(IU/L)
AlkPhos(IU/L)
0 1 2 3 4 6 8 1012 14 1618 20 222425 2848 56 60
ALT
Alk Phos
HCV RNA
55. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Sofosbuvir + RBV for Treatment of
Post-LT HCV Recurrence
Ongoing prospective,
multicenter, single-arm,
open-label pilot study
– Median time since LT: 4.3 yrs
(range: 1.02-10.6)
– CTP ≤ 7 and MELD ≤ 17
– 83% GT1, 33% IL28B CC, 40%
with comp’d cirrhosis
SOF 400 mg/day + RBV
400-1200 mg/day for ≤ 24 wks
– RBV started at 400 mg/day and
increased based on hemoglobin
levels
Charlton MR, et al. AASLD 2013. Abstract LB-2. Reproduced with permission.
Virologic Response Rates
*1 patient still on treatment.
†
4 patients had not reached SVR4 visit.
Wk 4 EOT* SVR4
Response(%)
100
80
60
40
20
0
100 100
77
40/40 39/39 27/35†
56. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Other Studies Recruiting
Sofosbuvir/ledipasvir FDC + RBV for 12 or 24 wks in
patients with advanced liver disease or posttransplantation
recurrence[1]
Simeprevir + daclatasvir + RBV for 24 wks in genotype 1b
patients with posttransplantation recurrence[2]
ABT-450/RTV/ABT-267 FDC + ABT-333 + RBV for 24 wks
in liver transplantation recipients[3]
1. ClinicalTrials.gov. NCT01938430. 2. ClinicalTrials.gov. NCT01938625. 3. ClinicalTrials.gov.
NCT01782495.
57. clinicaloptions.com/hepatitis
Clinicians and Faculty Define Strategies for the Next Era of HCV Therapy
Conclusions
Pre- and post-LT patients greatest challenge to eradication
of HCV
– Recent data encouraging
– Significant challenges remain
58. Go Online for More
From This Program!
CME-certified module that goes in-depth on each of the key questions
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clinicaloptions.com/shaping
Editor's Notes
GT, genotype; HCV, hepatitis C virus; P/R, peginterferon/ribavirin.
DAA, direct-acting antiviral; HCV, hepatitis C virus.
HCV, hepatitis C virus.
DAA, direct-acting antiviral; HBV, hepatitis B virus; HCV, hepatitis C virus.
GT, genotype; HCV, hepatitis C virus; PI, protease inhibitor; RBV, ribavirin; SVR4, sustained virologic response rate at 4 weeks posttreatment; SVR12, sustained virologic response rate at 12 weeks posttreatment.
For more information on this study, review the CCO Capsule Summary at: http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Amsterdam%202013/Viral%20Hepatitis/Capsules/1417.aspx.
CTP, Child-Turcotte-Pugh; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; MMF, mycophenolate mofetil; RBV, ribavirin; SOF, sofosbuvir.
For more information about this study, please see the CCO Capsule Summary at:
http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/AASLD%202013/Other%20Highlights/Capsules/213.aspx
HCV, hepatitis C virus; LT, liver transplantation; TND, target not detected.
For more information about this study, please see the CCO Capsule Summary at:
http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/AASLD%202013/Other%20Highlights/Capsules/213.aspx