Anti-HIV drug simulation offers 'realistic' tool to predict drug resistance and viral mutationSeptember 02, 2012
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.
Johns Hopkins Medicine
Related Clinical Trials Articles:
Children as young as 8 years old with incurable cancer can reliably characterize the impact an experimental therapy has on their symptoms and quality of life -- even at the earliest stages of drug development -- making self-reported patient outcomes a potential new clinical trial endpoint.
Women who participate in obstetric and gynecology clinical trials experience improved health outcomes compared to those who are not involved in trials, according to research by Queen Mary University of London.
Clinical trials are now enrolling to provide the final tests for a University of Virginia-developed artificial pancreas to automatically monitor and regulate blood-sugar levels in people with type 1 diabetes.
Standards for authorizing first-time trials of drugs in humans are lax, and should be strengthened in several ways, McGill University researchers argue in a paper published today in Nature.
The National Cancer Institute (NCI) today launched a new drug formulary (the 'NCI Formulary') that will enable investigators at NCI-designated Cancer Centers to have quicker access to approved and investigational agents for use in preclinical studies and cancer clinical trials.
Racial and ethnic groups can be underrepresented in medical research.
Researchers at the University of Liverpool have developed a new international guideline to help standardize how results from clinical trial studies are reported.
The number of cardiovascular drugs in the research pipeline has declined across all phases of development in the last 20 years even as cardiovascular disease has become the No.
Clinical research often excludes females from their trials under the assumption that 'one size fits all,' that a painkiller or antidepressant will be equally effective in subjects of either sex, but a growing number of scientists are criticizing this approach.
Clinical trials in children commonly go either uncompleted or unpublished, finds a comprehensive study conducted by researchers at Boston Children's Hospital.
Related Clinical Trials Reading:
Clinical Trials, Second Edition: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH Guidelines
by Tom Brody PhD (Author)
Clinical Trials, Second Edition, offers those engaged in clinical trial design a valuable and practical guide. This book takes an integrated approach to incorporate biomedical science, laboratory data of human study, endpoint specification, legal and regulatory aspects and much more with the fundamentals of clinical trial design. It provides an overview of the design options along with the specific details of trial design and offers guidance on how to make appropriate choices. Full of numerous examples and now containing actual decisions from FDA reviewers to better inform trial... View Details
Fundamentals of Clinical Trials
by Lawrence M. Friedman (Author), Curt D. Furberg (Author), David L. DeMets (Author), David M. Reboussin (Author), Christopher B. Granger (Author)
This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise. A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded. Many contemporary clinical trial examples have been added. There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing and... View Details
A Concise Guide to Clinical Trials
by J. Rick Turner PhD (Author)
Biopharmaceutical drugs improve the health and well-being of people across the globe on a scale that is unrivaled by any other medical intervention. Before these drugs can be prescribed for patients by their doctors, they have to be approved for marketing by a regulatory agency. To gain marketing approval, drugs must go through an extremely rigorous process that investigates their safety and efficacy, the process of New Drug Development. The last stage of this long, complex, and expensive process involves conducting clinical trials, the topic of this book. Successfully conducting... View Details
Clinical Trials: A Methodologic Perspective (Wiley Series in Probability and Statistics)
by Steven Piantadosi (Author)
Presents elements of clinical trial methods that are essential in planning, designing, conducting, analyzing, and interpreting clinical trials with the goal of improving the evidence derived from these important studies
This Third Edition builds on the text’s reputation as a straightforward, detailed, and authoritative presentation of quantitative methods for clinical trials. Readers will encounter the principles of design for various types of clinical trials, and are then skillfully guided through the complete process of planning the experiment, assembling a... View Details
Clinical Trials: What Patients and Healthy Volunteers Need to Know
by Lorna Speid Ph.D (Author)
Every year, hundreds of thousands of healthy volunteers and patients worldwide undertake the journey through the maze that can be clinical trials. Research participants take part in clinical trials for a variety of reasons. The healthy volunteers may be seeking extra money to pay off college tuition, or they may know someone who is suffering and would potentially benefit from the results of the trial. The patient who is terminally ill might participate in a clinical trial simply as a last hope for a cure. Whatever the goals, though, most participants will experience the same sense of... View Details
A Clinical Trials Manual From The Duke Clinical Research Institute: Lessons from a Horse Named Jim
by Margaret Liu (Author), Kate Davis (Author)
"The publication of the second edition of this manual comes at an important juncture in the history of clinical research. As advances in information technology make it possible to link individuals and groups in diverse locations in jointly seeking the answers to pressing global health problems, it is critically important to remain vigilant about moral and ethical safeguards for every patient enrolled in a trial. Those who study this manual will be well aware of how to ensure patient safety along with fiscal responsibility, trial efficiency, and research integrity."
—Robert... View Details
Clinical Trials: A Practical Approach
by Stuart J. Pocock (Author)
This comprehensive, unified text on the principles and practice of clinical trials presents a detailed account of how to conduct the trials. It describes the design, analysis, and interpretation of clinical trials in a non-technical manner and provides a general perspective on their historical development, current status, and future strategy. Features examples derived from the author's personal experience. View Details
Fundamentals of Clinical Trials
by Lawrence M. Friedman (Author), Curt D. Furberg (Author), David L. DeMets (Author)
The randomized control clinical trial has become the gold standard scientific method for the evaluation of pharmaceuticals, biologics, devices, procedures and diagnostic tests. This trial design has been successfully used in both therapeutic and disease prevention trials. It is superior to alternative designs by eliminating several sources of bias which exist in those designs. This role has evolved over the past three decades in a number of disease areas including cardiology, opthalmology, cancer and AIDS. While the specifics of using the randomized control design for a specific intervention... View Details
Designing Clinical Research
by Dr. Stephen B Hulley MD MPH (Author), Steven R Cummings MD (Author), Warren S Browner MD MPH (Author), Deborah G Grady MD MPH (Author), Thomas B Newman MD MPH (Author)
Publisher’s Note: Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product.
Designing Clinical Research has been extensively revised and continues to set the standard as a practical guide for doctors, nurses, pharmacists, and other health professionals involved in all forms of clinical, translational, and public health research. It presents advanced epidemiologic concepts in a reader-friendly way, and suggests common sense approaches to the challenging... View Details
Clinical Trial Data Analysis Using R and SAS, Second Edition (Chapman & Hall/CRC Biostatistics Series)
by Ding-Geng (Din) Chen (Author), Karl E. Peace (Author), Pinggao Zhang (Author)
Review of the First Edition
"The goal of this book, as stated by the authors, is to fill the knowledge gap that exists between developed statistical methods and the applications of these methods. Overall, this book achieves the goal successfully and does a nice job. I would highly recommend it …The example-based approach is easy to follow and makes the book a very helpful desktop reference for many biostatistics methods."
―Journal of Statistical Software
Clinical Trial Data Analysis Using R and SAS, Second Edition provides a thorough... View Details