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


Targeted therapy shows effectiveness against a subtype of the brain tumor medulloblastoma
A targeted therapy already used to treat advanced skin cancer is also effective against the most common subtype of the brain tumor medulloblastoma in adults and should be considered for treatment of newly diagnosed patients, according to research led by St. Jude Children's Research Hospital.

Patient cancer cells help to test treatments
A study, published today in Cell, demonstrates the power of organoids to capture, in three dimensions, the multiple mutations that occur in tumours.

TGen-UCSF study in Neuro-Oncology provides comprehensive look at brain cancer treatments
Led by the Translational Genomics Research Institute (TGen) and UC San Francisco (UCSF), a comprehensive genetic review of treatment strategies for glioblastoma brain tumors was published today in the Oxford University Press journal Neuro-Oncology.

Researchers make key malarial drug-resistence finding
According to the World Health Organization's 2014 World Malaria Report, there are an estimated 198 million cases of malaria worldwide with 3.3 billion people at risk for contracting the infection.

Red Journal's May issue focuses on the vital role of RT in modern lymphoma treatment
The "Radiation and the Modern Management of Lymphoma" issue (May 1, 2015) of the International Journal of Radiation Oncology * Biology * Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO), is focused on the integral role of radiation therapy in current lymphoma treatment.

Restoring cellular energy signals may treat mitochondrial diseases in humans
Rooted in malfunctions in the tiny power plants that energize our cells, mitochondrial disorders are notoriously complex and variable, with few effective treatments. Now, novel findings in microscopic worms may hold great promise for children and adults with mitochondrial disorders.

A call to action for 2 cancer research fronts to join forces
Since President Nixon declared the "War on Cancer" in 1971, scientists have been united in a quest to find all gene deletions, insertions, or duplications that can cause an otherwise ordinary cell to divide uncontrollably.

Researchers find new approach to treat drug-resistant HER2-positive breast cancer
Resistance to therapy is a major problem in the cancer field. Even when a treatment initially works, the tumors often find ways around the therapy. Using human cell lines of the HER2-positive breast cancer subtype, researchers from the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center have detailed the surprising ways in which resistance manifests and how to defeat it before it happens.

Review highlights potential of cancer immunotherapy plus targeted therapy
The prospect of combining genomically targeted therapies with drugs that free the immune system to attack cancer suggests "we are finally poised to deliver curative therapies to cancer patients," researchers at The University of Texas MD Anderson Cancer Center note in a review in the April 9 edition of Cell.

Central signaling pathway in lymphoma can be blocked successfully
Cancer researchers from the University of Zurich have identified a key signaling pathway in B-cell lymphoma, a malignant type of blood cancer.
More Combination Therapies Current Events and Combination Therapies News Articles

basic clinical massage therapy: a combination of anatomy and Therapy (Hardcover)

basic clinical massage therapy: a combination of anatomy and Therapy (Hardcover)
by ZHAN MU SI ?H ?KE LAI (Author)


brand new

Combination Therapy in Hypertension

Combination Therapy in Hypertension
by Joel M. Neutel (Author)


For over 30 years, the stepped care approach has been used in the management and treatment of hypertension. This approach advocates the use of initial monotherapy to reach the desired blood pressure, and the subsequent use of additional drugs with complementary modes of action, until the target BP is achieved. However, current control rates for hypertension suggest that such an approach may be outdated and no longer effective in the management of hypertension. Clinical trials have shown that more than 50% of patients require a combination of drug therapies to achieve their target BP. Some proponents of combination therapy have argued that the risk of adverse side effects and non-compliance will be lower than that compared to monotherapy, which initially requires higher doses to be...

Hematology - Oncology Therapy

Hematology - Oncology Therapy
by Michael Boyiadzis (Author), James Frame (Author), David R. Kohler (Author), Tito Fojo (Author)


The Essential Therapy Guide to Cancer, Hematologic Disorders, and Supportive Care--Updated with the Latest Treatment Regimens More than 500 treatment regimens Hematology-Oncology Therapy, Second Edition is an up-to-date, comprehensive therapy guide that delivers more than 500 treatment regimens in a succinct, uniform manner. The unique tabular design allows you to instantly locate and implement the proper treatment regimen. Supported by the latest practice guidelines, peer-reviewed literature, and the opinion of experts, Hematology-Oncology Therapy integrates extensive information that is critical to both office- and hospital-based practice of hematology and oncology. Hematology-Oncology Therapy is divided into three sections: Oncology:
Provides detailed information about the...

Combination Therapy In Dyslipidemia

Combination Therapy In Dyslipidemia
by Maciej Banach (Editor)


Comprising contributions from leading lipidologists from around the world, this book presents the latest and most comprehensive knowledge on the different options for combination therapy of dyslipidemia and includes discussion of future therapies that are currently in late stages of clinical evaluation. Dyslipidemia is a leading cause of cardiovascular morbidity and mortality and most patients with this condition fail to achieve adequate control of their serum lipid levels with monotherapy. However, recent US and European guideline recommendations, based on randomized, controlled trials, fail to discuss combination therapy options for patients with dyslipidemia.Statins remain the mainstay of drug therapy for hyperlipidemia and chapters in this book specifically examine the role of add-on...

Medical Nutrition Therapy: A Case Study Approach

Medical Nutrition Therapy: A Case Study Approach
by Marcia Nelms (Author), Sara Long Roth (Author)


Building a bridge from classroom to clinical practice, this casebook is composed of 34 realistic case studies appropriate for introductory and advanced level courses in nutrition and diet therapy. Each case study uses the medical record as its structure. The student "solves the case" by using the information provided such as hospital admission data, laboratory test results, intake/output records, and the physician's progress notes. The case is followed by a series of questions that focus on pathophysiology; assessment; clinical, nutritional and behavioral outcomes; interventions; and appropriate follow-up for the patient. This "real world" approach helps to prepare the student for the professional setting. Objectives for student learning within each case are built around the nutrition...

Abrams' Clinical Drug Therapy: Rationales for Nursing Practice

Abrams' Clinical Drug Therapy: Rationales for Nursing Practice
by Geralyn Frandsen EdD RN (Author), Sandra Smith Pennington RN PhD (Author)


This popular core nursing pharmacology textbook provides unique coverage of nursing interventions for drug therapy with related rationales. Highly praised for its organized and readable presentation, the text explains the "why" behind each nursing action, and emphasizes how drugs work differently in different patients.  The 10th edition has a new fresh design and approach with an added focus on patient safety integrated into the text.  Included in this package is Lippincott's Photo Atlas of Medication Administration (ISBN 9781451112481) which uses the nursing process format to provide step-by-step nursing skills.

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.

Studio Art Therapy: Cultivating the Artist Identity in the Art Therapist (Arts Therapies)

Studio Art Therapy: Cultivating the Artist Identity in the Art Therapist (Arts Therapies)
by Catherine Hyland Moon (Author)


Arguing that the profession of art therapy has its roots in the studio environment, Catherine Moon proposes that it is now time to reclaim these roots, and make art once again central to art therapy. She suggests that there has been a tendency for art therapy not merely to interact with and be enriched by other perspectives - psychological, social, anthropological and transpersonal - but to be subsumed by them. For this reason she makes a clear distinction between using art in one's practice of therapy, and working from an art-based model. This book presents a model of art therapy where the products and processes of art constitute the core of the model, rather than serving as the impetus for adaptations of other theories of counseling or therapy. It addresses how an arts-based approach...

Nutrition and Diet Therapy

Nutrition and Diet Therapy
by Linda Kelly DeBruyne (Author), Kathryn Pinna (Author), Eleanor Noss Whitney (Author)


NUTRITION AND DIET THERAPY, 8th Edition, is unique in its organization by diets rather than by organ systems or disease states and distinguishes itself through rich pedagogical features that require students to apply their knowledge as they learn it. This text provides core nutrition concepts and up-to-date clinical content at a level that is accessible to the range of health care team members who are responsible for a client's nutrition needs. NUTRITION AND DIET THERAPY provides the basic facts and a wealth of practical information readers need to assume their responsibility for nutrition care.

Williams' Basic Nutrition & Diet Therapy, 14e (LPN Threads)

Williams' Basic Nutrition & Diet Therapy, 14e (LPN Threads)
by Staci Nix MS RD CD (Author)


Williams’ Basic Nutrition & Diet Therapy is a market leader for a reason - it provides coverage of hot topics, emerging trends, and cutting edge research, plus all the essentials for providing the best nutrition care. You’ll love it for the clear, conversational writing style and vivid illustrations that guide you from fundamental concepts of nutrition to the application of those concepts in clinical practice. UNIQUE! Content threads share features with other LPN/LVN titles from Elsevier for a consistent learning experience.Case studies in clinical care chapters focus on related patient care problems.Critical thinking questions challenge you to analyze, apply, and combine concepts.Cultural Considerations boxes discuss how a patient's culture can affect nutritional concepts in...

© 2015 BrightSurf.com