Anti-HIV drug simulation offers 'realistic' tool to predict drug resistance and viral mutationSeptember 04, 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.
For additional information, go to:
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