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


Type 2 diabetes: Added benefit of canagliflozin plus metformin is not proven
The fixed combination of canagliflozin with metformin (trade name: Vokanamet) has been approved since April 2014 for adults with type 2 diabetes mellitus in whom diet and exercise do not provide adequate glycaemic control.

Gene sequencing projects link two mutations to Ewing sarcoma subtype with poor prognosis
An international collaboration has identified frequent mutations in two genes that often occur together in Ewing sarcoma (EWS) and that define a subtype of the cancer associated with reduced survival.

Text messages could be useful tool in fight against malaria
Each year, malaria kills over 600,000 people, more than half of them children. In a study published today in PLOS ONE , researchers with the non-profit Innovations for Poverty Action (IPA) and Harvard University found that simple text message reminders to take malaria medication can help in the fight against the disease by boosting the rates at which patients complete their medication regimen.

New hypothyroidism treatment guidelines from American Thyroid Association
Levothyroxine (L-T4), long the standard of care for treating hypothyroidism, is effective in most patients, but some individuals do not regain optimal health on L-T4 monotherapy.

Targeted combination therapy halts disease, extends life in advanced melanoma patients
A world-first study in today's New England Journal of Medicine heralds the efficacy of a targeted combination drug therapy after reporting major declines in the risk of disease progression and death in people with metastatic melanoma.

Protein found to block benefits of vitamin A cancer therapy
Retinoic acid is a form of vitamin A that is used to treat and help prevent the recurrence of a variety of cancers, but for some patients the drug is not effective.

Triple therapy revs up immune system against common brain tumor
A triple therapy for glioblastoma, including two types of immunotherapy and targeted radiation, has significantly prolonged the survival of mice with these brain cancers, according to a new report by scientists at the Johns Hopkins Kimmel Cancer Center.

Researchers uncover common heart drug's link to diabetes
McMaster University researchers may have found a novel way to suppress the devastating side effect of statins, one of the worlds' most widely used drugs to lower cholesterol and prevent heart disease.

Clinical trials designed to block autophagy in multiple cancers show promise
In the largest group of results to date, researchers from Penn Medicine's Abramson Cancer Center and other institutions have shown in clinical trials that the malaria drug hydroxychloroquine (HCQ) blocked autophagy in a host of aggressive cancers-glioblastoma, melanoma, lymphoma and myeloma, renal and colon cancers-and in some cases helped stabilize disease.

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).
More Combination Therapies Current Events and Combination Therapies News Articles

Antiepileptic Drugs: Combination Therapy and Interactions

Antiepileptic Drugs: Combination Therapy and Interactions
by Jerzy Majkowski (Editor), Blaise F. D. Bourgeois (Editor), Philip N. Patsalos (Editor), Richard H. Mattson (Editor)


This book reviews the use of antiepileptic drugs focusing on the interactions between these drugs and between antiepileptics and other drugs. These interactions can be beneficial or can cause harm. The aim of this book is to increase awareness of the possible impact of combination pharmacotherapies. Pharmacokinetic and pharmacodynamic interactions are discussed supported by clinical and experimental data. The book consists of five sections covering the general concepts and advantages of combination therapies, the principles of drug interactions, the mechanisms of interactions, drug interactions in specific populations or in patients with co-morbid health conditions, and concludes with a look at the future directions for this field of research. The book will be of interest to all who...

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 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,...

Conn's Current Therapy 2015, 1e

Conn's Current Therapy 2015, 1e
by Edward T. Bope MD (Author), Rick D. Kellerman MD (Author)


Ideal for busy medical practitioners who need quick, reliable answers, Conn's Current Therapy 2015 is an easy-to-use, in-depth guide that focuses solely on the most up-to-date treatment protocols for common complaints, acute disease and chronic illness. Drs. Edward T. Bope and Rick D. Kellerman present the expertise and knowledge of hundreds of skilled international leaders on evidence-based clinical management options. With key diagnostic points and treatment recommendation tables, you'll have quick access to the information you need to make accurate clinical decisions. Find answers quickly so you can dedicate more time to treatment with practical and accurate advice by renowned international experts on diagnosis and management, delivered via a templated, at-a-glance approach. Take it...

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.

Insights of a Senior Acupuncturist

Insights of a Senior Acupuncturist
by Miriam Lee (Author)


This book details the ingenious use of only five major acupuncture points to effectively treat a wide variety of ills. Written by one of the most experienced and well-known acupuncturists in California, this book is a must read for students and practitioners alike. It is written in a deceptively simple, unpretentious style characteristic of its author, but readers should not be deceived. The theory it contains is profound, stemming from the Four Great Masters of the Jin-Yuan dynasties.

Healing Touch: Enhancing Life through Energy Therapy

Healing Touch: Enhancing Life through Energy Therapy
by Diane Wardell (Author), Sue Kagel (Author), Lisa Anselme (Author)


Andrew Weil, MD, author of Natural Healing  endorses this book! "I believe that energy therapies will be part of medicine and health care of the future. Healing Touch, supported by a body of research, has been part of the curriculum of the University of Arizona Center for Integrative Medicine since its inception, and I refer patients to it for enhancement of health and healing. This informative and thorough book is an excellent introduction to the field."
--Andrew Weil, MD, author of Natural Healing                                                       Enhance your Life! Learn how Healing Touch can benefit you personally or professionally. This book is for those who are curious, interested, work in health care or healing arts...

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...

Cognitive Therapy of Personality Disorders, Third Edition

Cognitive Therapy of Personality Disorders, Third Edition
by Aaron T. Beck MD (Editor), Denise D. Davis Phd (Editor), EdD Arthur Freeman EdD (Editor)


This widely used practitioner resource and training tool is the definitive work on understanding and treating personality disorders from a cognitive-behavioral therapy (CBT) perspective. The prominent editors and contributors explain the nature of personality disorders and why they are so challenging to treat. Chapters addressing 12 specific disorders are organized around vivid, instructive clinical examples. The book provides up-to-date scientific knowledge about each disorder and describes effective strategies for differential diagnosis, case conceptualization, implementing individualized CBT interventions, and overcoming roadblocks.

New to This Edition
*Incorporates cutting-edge clinical approaches and research; expands the cognitive theory of personality disorder.
...

Trigger Point Therapy for Headaches and Migraines: Your Self -Treatment Workbook for Pain Relief

Trigger Point Therapy for Headaches and Migraines: Your Self -Treatment Workbook for Pain Relief
by Valerie DeLaune LAc (Author)


I have such a bad headache! For many of us, this is an oft repeated cry of anguish. Statistics about headaches and migraines are downright astonishing: One in six people have frequent headaches, and of those, one in ten suffers from migraines. You are not alone. Headaches and migraines result in more than 10 million doctor visits each year. If you struggle frequently with headache pain, this book offers a welcome solution. Trigger point therapy is an effective self-care approach you can use to get relief from headache pain.Trigger points form in a portion of the muscle cell where blood flow is reduced and metabolic wastes are not being exchanged for oxygen and nutrients. When enough trigger points are located together, they can form palpable knots in the tissue. Trigger points can cause...

© 2014 BrightSurf.com