Science Current Events | Science News | Brightsurf.com
 

Anti-HIV drug simulation offers 'realistic' tool to predict drug resistance and viral mutation

September 04, 2012
Computer model should help develop better anti-HIV drug combination therapies

Pooling data from thousands of tests of the antiviral activity of more than 20 commonly used anti-HIV drugs, AIDS experts at Johns Hopkins and Harvard universities have developed what they say is the first accurate computer simulation to explain drug effects. Already, the model clarifies how and why some treatment regimens fail in some patients who lack evidence of drug resistance. Researchers say their model is based on specific drugs, precise doses prescribed, and on "real-world variation" in how well patients follow prescribing instructions.

Johns Hopkins co-senior study investigator and infectious disease specialist Robert Siliciano, M.D., Ph.D., says the mathematical model can also be used to predict how well a patient is likely to do on a specific regimen, based on their prescription adherence. In addition, the model factors in each drug's ability to suppress viral replication and the likelihood that such suppression will spur development of drug-resistant, mutant HIV strains.

"With the help of our simulation, we can now tell with a fair degree of certainty what level of viral suppression is being achieved - how hard it is for the virus to grow and replicate - for a particular drug combination, at a specific dosage and drug concentration in the blood, even when a dose is missed," says Siliciano, a professor at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. This information, he predicts, will remove "a lot of the current trial and error, or guesswork, involved in testing new drug combination therapies."

Siliciano says the study findings, to be reported in the journal Nature Medicine online Sept. 2, should help scientists streamline development and clinical trials of future combination therapies, by ruling out combinations unlikely to work.

One application of the model could be further development of drug combinations that can be contained in a single pill taken once a day. That could lower the chance of resistance, even if adherence is not perfect. Such future drug regimens, he says, will ideally strike a balance between optimizing viral suppression and minimizing risk of drug resistance.

Researchers next plan to expand their modeling beyond blood levels of virus to other parts of the body, such as the brain, where antiretroviral drug concentrations can be different from those measured in the blood. They also plan to expand their analysis to include multiple-drug-resistant strains of HIV.

Besides Siliciano, Johns Hopkins joint medical-doctoral student Alireza Rabi was a co-investigator in this study. Other study investigators included doctoral candidates Daniel Rosenbloom, M.S.; Alison Hill, M.S.; and co-senior study investigator Martin Nowak, Ph.D. - all at Harvard University.

Funding support for this study, which took two years to complete, was provided by the National Institutes of Health, with corresponding grant numbers R01-MH54907, R01-AI081600, R01-GM078986; the Bill and Melinda Gates Foundation; the Cancer Research Institute; the National Science Foundation; the Howard Hughes Medical Institute; Natural Sciences and Engineering Research Council of Canada; the John Templeton Foundation; and J. Epstein.

Currently, an estimated 8 million of the more than 34 million people in the world living with HIV are taking antiretroviral therapy to keep their disease in check. An estimated 1,178,000 in the United States are infected, including 23,000 in the state of Maryland.

###

For additional information, go to:

http://www.hopkinsmedicine.org/pharmacology_molecular_sciences/faculty/bios/siliciano.html

http://www.hhmi.org/research/investigators/siliciano_bio.html

http://www.nature.com/nm/index.html

Johns Hopkins Medicine


Related Combination Therapies Current Events and Combination Therapies News Articles


Three new studies help clarify optimal use of combination therapy in chronic hepatitis B patients
Three new studies presented today at the International Liver CongressTM 2014 have helped clarify the optimal use of combination therapy with peginterferon and nucleoside analogues (NUCs) to achieve the best treatment outcomes in patients with chronic hepatitis B (CHB).

USF study finds stem cell combination therapy improves traumatic brain injury outcomes
Umbilical cord cell and growth factor treatment tested in animal models could offer hope for millions, including U.S. war veterans with traumatic brain injuries

Detecting levels of antibiotics in blood paves the way to individualized treatment
A new methodology for rapidly measuring the level of antibiotic drug molecules in human blood serum has been developed, paving the way to applications within drug development and personalised medicine.

Cochrane review of dihydroartemisinin-piperaquine for treating uncomplicated malaria
'Dihydroartemisinin-piperaquine is more effective than artemether-lumefantrine, and has fewer side effects than artesunate-mefloquine' concludes a systematic review published by the Cochrane Infectious Disease Group, hosted by LSTM.

Malaria treatment could improve in children
An analysis of patients from across the malaria endemic world suggests that a key antimalarial treatment could be improved by better dosing in young children.

Drug trial for top parasitic killer of the Americas: Mixed results, new evidence to improve therapy
According to results of the first-ever Phase 2 clinical trial in Bolivia, conducted by the Drugs for Neglected Diseases initiative (DNDi), the experimental drug candidate E1224 showed good safety and was effective at clearing the parasite that causes Chagas disease, but had little to no sustained efficacy one year after treatment as a single medication.

Team-based approaches needed to fight high blood pressure
Uncontrolled high blood pressure rates continue to grow despite the availability of proven treatments, but collaborative approaches can be effective in fighting this deadly disease, according to a science advisory from the American Heart Association, the American College of Cardiology and the Centers for Disease Control and Prevention.

McMaster scientists unlock secrets of diabetes drug
About 120 million people around the world with Type 2 diabetes - and two million in Canada - take the drug metformin to control their disease.

Diabetes drug metformin with chemo and radiation may improve outcomes in lung cancer patients
Treating aggressive lung cancer with the diabetes drug metformin along with radiation and chemotherapy may slow tumor growth and recurrence, suggests new preliminary findings from researchers at the Perelman School of Medicine at the University of Pennsylvania being presented during an oral abstract session October 28 at the 15th World Conference on Lung Cancer.

Study Explains Why Diabetic Retinopathy Is Difficult to Treat
Damage to the retina due to diabetes can be ameliorated only partially, despite treatment with the standard drug metformin.
More Combination Therapies Current Events and Combination Therapies News Articles

Combination Therapy Versus Intensification of Statin Monotherapy: An Update: Comparative Effectiveness Review Number 132

Combination Therapy Versus Intensification of Statin Monotherapy: An Update: Comparative Effectiveness Review Number 132
by U.S. Department of Health and Human Services (Author), Agency for Healthcare Research and Quality (Author)


Cardiovascular disease (CVD) includes conditions such as coronary heart disease, stroke, heart failure, arrhythmia, heart valve disease, congenital heart disease, and hypertension. The American Heart Association has estimated that CVD affects 83.6 million individuals in the U.S., contributes to 32.3% of deaths, and is a leading cause of disability. Atherosclerosis causes coronary heart disease (CHD), cerebrovascular disease, and peripheral artery disease. Abnormal lipoprotein metabolism predisposes individuals to atherosclerosis. Due to the consistent and robust association of higher LDL-c levels with atherosclerotic CVD across experimental and epidemiologic studies, therapeutic strategies to decrease risk have focused on LDL-c reduction as a primary goal. In contrast to LDL-c,...

Advances in Combination Therapy for Asthma and COPD

Advances in Combination Therapy for Asthma and COPD
by Jan Lotvall (Editor)


Aimed at specialists in respiratory medicine, this new book comprehensively reviews the variety of agents currently available for treatment of asthma, COPD, and other airway diseases and covers practical guidelines as well as challenges and complications in their use. Advances in Combination Therapy for Asthma and COPD is the first book to address the complexity of multi-agent therapy and deal with management issues in an integrated fashion.  A review of currently available agents and their applications, as well as new therapies soon to become available are outlined. Advantages of combined therapies and additional considerations that arise from multi-agent programs are highlighted.

Textbook of Facial Rejuvenation: The Art of Minimally Invasive Combination Therapy

Textbook of Facial Rejuvenation: The Art of Minimally Invasive Combination Therapy
by Nicholas J. Lowe (Editor), Alastair Carruthers (Editor), Jean Carruthers (Editor), Zoe Diana Draelos (Editor), Richard Glogau (Editor), Christopher Griffiths (Editor), Arnold W. Klein (Editor), Gary Lask (Editor)


In recent years the demand for rejuvenating treatments for the face has grown dramatically for both men and women. Alongside that demand, a wide variety of treatments have evolved, and a combination of different treatments can often result in much greater improvement than single-treatment approaches. With contributions from an impressive cast of international experts, Textbook of Facial Rejuvenation details current treatments, recommends approaches, and suggests how they may be tailored towards individual needs and combined for optimum results.

Mindfulness-Based Cognitive Therapy for Depression, Second Edition

Mindfulness-Based Cognitive Therapy for Depression, Second Edition
by Zindel V. Sega (Author), J. Mark G. Williams (Author), John D. Teasdale (Author), Jon Kabat-Zinn (Foreword)


This bestselling work, now in a new edition, has introduced tens of thousands of clinicians to mindfulness-based cognitive therapy (MBCT) for depression, an eight-week program with proven effectiveness. Step by step, the authors explain the "whys" and "how-tos" of conducting mindfulness practices and cognitive interventions that have been shown to bolster recovery from depression and prevent relapse. Clinicians are also guided to practice mindfulness themselves, an essential prerequisite to teaching others. More than 40 reproducible handouts are included. Purchasers get access to a companion website featuring downloadable audio recordings of the guided mindfulness practices (meditations and mindful movement), plus all of the reproducibles, ready to download and print in a convenient 8...

Healing the Gerson Way + The Beautiful Truth DVD Combination Pak

Healing the Gerson Way + The Beautiful Truth DVD Combination Pak
by Charlotte Gerson Beata Bishop (Author)


Healing the Gerson Way + The Beautiful Truth DVD - Combo Pak -- Healing the Gerson Way is a bestselling how-to guide for implementing Gerson Therapy. Updated in 2009, this 2nd edition includes new Gerson Therapy techniques, a new materials resource section, 91 pages of Gerson approved recipes and more. -- The Beautiful Truth DVD is a powerful cinematic presentation on the chemical and dietetic causes of various diseases and the benefits of Gerson Therapy. Follow 15 year old Garrett as he travels across the country meeting with cancer survivors who present their stories of healing by following The Gerson Therapy. Garrett also interviews scientists, doctors and researchers, who reveal that it is in the best interest of the multi-billion dollar medical industry to dismiss the notion of...

Transdermal Magnesium Therapy: A New Modality for the Maintenance of Health

Transdermal Magnesium Therapy: A New Modality for the Maintenance of Health
by Mark Sircus (Author)


This second edition of Transdermal Magnesium Therapy offers a full medical review of how magnesium affects cancer, the heart, diabetes, the emotions, inflammation, surgery, autism, transdermal medicine, and so much more.

Food Synergy: Unleash Hundreds of Powerful Healing Food Combinations to Fight Disease and Live Well

Food Synergy: Unleash Hundreds of Powerful Healing Food Combinations to Fight Disease and Live Well
by Elaine Magee (Author)


Over the past few years, scientists have made dramatic new breakthroughs in harnessing the healing power of foods. In addition to discovering which "superfoods" offer maximum health benefits, they now know that some nutrients pack a special healing wallop when eaten together rather than alone. In more than 25 books and her nationally syndicated newspaper column "The Recipe Doctor," popular food writer Elaine Magee has demonstrated a special gift for translating the science behind nutrition into easy-to-understand advice. Here, whether she is highlighting the latest news on phytochemicals or explaining why new lab studies suggest that tomatoes and broccoli work together to reduce prostate growth better than either vegetable alone, she not only details the best foods to eat and why—but...

Doing Couple Therapy: Craft and Creativity in Work with Intimate Partners (Guilford Family Therapy)

Doing Couple Therapy: Craft and Creativity in Work with Intimate Partners (Guilford Family Therapy)
by Robert Taibbi (Author)


Wise, compassionate, and highly practical, this engaging text covers the entire process of therapeutic work with couples, from opening sessions and assessment through skills building, core issues, and termination. Students and novice couple therapists learn effective strategies for intervening with couples of any age who are struggling with acute crises or longstanding conflicts and power struggles. Rich with sensitive, detailed case material, the book features numerous exercises that help readers identify and develop their own strengths as practitioners. Self-care strategies and tips for getting the most out of supervision are provided. Special topics include how to address couple issues with only one partner and couple therapy applications for chronic mental health problems....

© 2014 BrightSurf.com