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


Ancient anti-inflammatory drug salicylic acid has cancer-fighting properties
Scientists from the Gladstone Institutes have identified a new pathway by which salicylic acid--a key compound in the nonsteroidal anti-inflammatory drugs aspirin and diflunisal--stops inflammation and cancer.

Researchers reveal how a new class of drugs kills cancer cells
A team of Walter and Eliza Hall Institute researchers has worked out how a new class of anti-cancer drugs kills cancer cells, a finding that helps explain how cancer cells may become resistant to treatment.

A long-noncoding RNA regulates repair of DNA breaks in triple-negative breast cancer cells
The discovery of long non-coding RNA (lncRNA) has dramatically changed the understanding of the biology of diseases such as cancer.

Researchers find method that could resurrect an abandoned pancreatic cancer targeted drug
Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2020.

Curbing malaria resistance with multiple therapies
In order to preserve first-line drugs for treating malaria, multiple combination therapies should be deployed within a population to prevent resistance from developing, according to Maciej Boni from the Centre for Tropical Medicine and Global Health, University of Oxford, UK, and colleagues in a Policy Forum article published in this week's PLOS Medicine.

Medication protects fertility and defense system during chemotherapy
While targeted cancer treatments have reduced side effects and improved efficacy, chemotherapy remains the backbone of combination therapies for many forms of cancer.

UA-led research: Prevention of macular degeneration possible
A University of Arizona-led study on age-related macular degeneration - the eye disease that gradually destroys the ability to read, drive, write and see close-up in 30 percent of older Americans - likely will lead to a way to delay or prevent the disease, researchers say.

Treatment restores some function in animal models of spinal muscular atrophy
In work involving several new generations of mouse model development, Jackson Laboratory (JAX) researchers have tested a therapeutic intervention for spinal muscular atrophy (SMA) that restores some function lost due to a mutation in one gene (SMN1) and amplifies the levels of protective genes (SMN2).

Professor Janet Hemingway, outlines 15 years of malaria interventions in Africa
In an editorial in the weekly science journal Nature, LSTM's Director, Professor Janet Hemingway, looks at how the last 15 years of control measures have led to massive reductions in disease prevalence in Africa since 2000.

Breakthrough study demonstrates survival advantage with immune checkpoint inhibitor for advanced kidney cancer patients
For the first time, an immune checkpoint inhibitor has been proven to increase survival among patients with advanced renal cell carcinoma (RCC), a patient population for whom treatment options are currently limited.
More Combination Therapies Current Events and Combination Therapies News Articles

Acupuncture Point Combinations: The Key to Clinical Success, 1e

Acupuncture Point Combinations: The Key to Clinical Success, 1e
by Jeremy Ross (Author)


This book covers the principles and practice of combining acupuncture points - expanding a practitioner's repertoire and increasing their skills - enabling them to use a balanced and appropriate choice of points in the treatment of patients. Information onthe combination of the main points of the fourteen channels is covered in the book prior to outlining specific point combinations for selected disease syndromes. Discussion of combining points according to dermatome theory and according to the energy centres of the body is also discussed, as is combining points for the mind end emotions, and for lifestyle and behaviour. No existing book covers this aspect of clinical practice in such thorough and wide-ranging detail.

Combination Therapies: Biological Response Modifiers in the Treatment of Cancer and Infectious Diseases

Combination Therapies: Biological Response Modifiers in the Treatment of Cancer and Infectious Diseases
by E. Garaci (Editor), Allan L. Goldstein (Editor)


Over the past decade many of the key lymphokines, hormones and growth factors that help regulate the immune system have been defined. These molecules, termed biological response modifiers (BRMs) , have been sequenced, synthesized and produced in large enough quantities to test in animals and humans resulting in the development of new approaches to the treatment of human disease, in particular, cancers and infectious diseases. Advances in this area have also led to rethinking therapies against a range of autoimmune disorders and other diseases associated with immune and endocrine imbalances. BRMs currently are being applied clinically as both primary and adjunctive therapy to enhance the effectiveness of traditional treatments by maximizing their activities and to protect critical tissues...

Combination Therapies 2: Biological Response Modifiers in the Treatment of Cancer and Infectious Diseases

Combination Therapies 2: Biological Response Modifiers in the Treatment of Cancer and Infectious Diseases
by E. Garaci (Editor), Allan L. Goldstein (Editor)


The 2nd International Symposium on Combination Therapies brought together several hundred of the leading researchers, scientists and clinicians in this area to discuss new and emerging uses for biological response modifiers (BRM's) in the treatment of cancer and infectious diseases. The meeting was held during May 1-3, 1992 in Acireale, Sicily (Italy). It was hosted by Professor G. Nicoletti CU. of Catania) and organized by the Institute for Advanced Studies in Immunology and Aging (Washington, D. C. ) in collaboration with the University of Rome "Tor Vergata," the University of Catania and The George Washington University Medical Center. The synergy exhibited between BRM's and conventional therapies including bone marrow and other lymphoid cell transplants is a rapidly expanding area...

Novel Combination Therapies for Prostate Cancer Treatment: Pharmacological Investigation

Novel Combination Therapies for Prostate Cancer Treatment: Pharmacological Investigation
by Elia Hristova (Author), Pietro Marini (Author), Maria-Grazia Cascio (Author)


Prostate cancer is a prevalent disease in men. It usually begins as androgen-dependent and develops into an androgen-independent phenotype with time. CBG, a known serotonin receptor antagonist, has potential beneficial pharmacological effects on androgen-independent tumour development. It has been proposed that DHEA, the ethanolamide derivative of the polyunsaturated fatty acid DHA, is more potent at inhibiting prostate cancer cell growth and proliferation than its parent compound. The androgen-sensitive LNCaP cell line was used for an in vitro cell viability assay in this project. The focus of the study was to investigate the pharmacological effects of novel combination therapies in prostate cancer. Nine different combinations between CBG and DHEA were used to treat the cells. Based on a...

3 Day Cleansing Program: Mucusless Diet & Herbal Combinations

3 Day Cleansing Program: Mucusless Diet & Herbal Combinations
by Christopher Publications


Learn the safest program for detoxification through simple juice cleansing revitalization by nourishing the body with live foods found in the “mucusless diet.” Understand how to bless body and mind with vitality, strength and immunity. Also contained are 63 of Dr. Christopher’s famous herbal combinations with descriptions of their components, uses and benefits.

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.

What to Eat for How You Feel: The New Ayurvedic Kitchen - 100 Seasonal Recipes

What to Eat for How You Feel: The New Ayurvedic Kitchen - 100 Seasonal Recipes
by Divya Alter (Author), William Brinson (Photographer), Susan Brinson (Photographer)


This indispensable kitchen companion brings the ancient art of delicious healthy cooking to the twenty-first century with flavors adapted for the contemporary Western palate.
 
Drawing on her many years of vegetarian cooking, catering, and teaching, in this book Divya Alter explains how to create flavorful meals with seasonal ingredients by applying Ayurvedic principles. With food combinations, methods of preparation, and healing spices customized for individual needs, this is an inspirational guide to achieving optimal health through a personalized way of living and eating.
 
This volume features 100 recipes for breakfasts, soups, salads, main dishes, one-pot meals, treats, and beverages in three seasonal-based chapters. It includes an ingredient guide along with...

Animal Mandala Coloring Pages: This Animal Mandala Coloring Pages book is fun for all Ages - Adults and Kids can Relax while   coloring a combination ... Mandalas on full size large Coloring Pages

Animal Mandala Coloring Pages: This Animal Mandala Coloring Pages book is fun for all Ages - Adults and Kids can Relax while coloring a combination ... Mandalas on full size large Coloring Pages
by Frances P Robinson (Author)


Enjoy a large variety of mandala and playful animal patterns that are ready to color. This design collection is good for hours of relaxing and can help get rid of stress. Features a large variety of designs that integrate all types of animals, and other creatures with mandalas. Fun for all ages. Want to relax? Buy this large 8.5" x 11" Animal Mandala Coloring Pages now.

Cat Mandala Coloring Book: Cat Mandala Coloring Book fun for all Ages - Adults and Kids can Relax while coloring a   combination of integrated Cats with Mandalas on full size large Coloring Pages

Cat Mandala Coloring Book: Cat Mandala Coloring Book fun for all Ages - Adults and Kids can Relax while coloring a combination of integrated Cats with Mandalas on full size large Coloring Pages
by Frances P Robinson (Author)


Enjoy a large variety of mandala and playful cat patterns that are ready to color. This design collection is good for hours of relaxing and can help get rid of stress. Features a large variety of designs that integrate all types of cats with mandalas. Fun for all ages. Want to relax? Buy this large 8.5" x 11" Cat Mandala Coloring Book now.

Acupressure and Homoeopathy Combinations in the Treatment of Common Ailments

Acupressure and Homoeopathy Combinations in the Treatment of Common Ailments
by Dr John R Cross (Author)


This is the second edition of this book that has been revamped and updated from the 'e' version of 2014. It covers the practice of self treatment using the twin aspects of acupressure and simple, easily available homoeopathic remedies. Twenty five common ailments are covered that include, sore neck, headache, stomach ache, cystitis, anxiety and worry.

© 2017 BrightSurf.com