EuResist

Last updated
EuResist
Initial release2006
Operating system Cross-platform
Website www.euresist.org

EuResist is an international project designed to improve the treatment of HIV patients by developing a computerized system that can recommend optimal treatment based on the patient's clinical and genomic data. [1] [2]

Contents

The project is part of the Virtual Physiological Human framework, funded by the European Commission. It started in 2006 with the formation of a consortium of several research institutes and hospitals in Europe and Israel. The consortium completed its commitment to the European Commission near the end of 2008, at which time the system became available online. A non-profit organization was consequently established by the main partners to maintain and improve the system.

Background

AIDS is a disease caused by the HIV retrovirus, which progressively reduces the effectiveness of the immune system, leading to infections and ultimately death.

More than 30 different drugs exist for treating HIV patients. Antiretroviral drugs can disrupt the virus's replication process causing its numbers to decrease dramatically. While the virus cannot be eradicated completely, in small numbers it is harmless. Usually a patient is given a combination of three or four drugs, a treatment known as highly active antiretroviral therapy, or HAART. The main reason such a treatment might fail is the development of mutated strands of the virus, resistant to one or more of the prescribed drugs.

Thus an important consideration when choosing treatment for a patient is to prescribe those drugs to which the particular patient's virus strands are most susceptible. One way to achieve that is to extract virus samples from the patient's blood and test them against all possible drugs. Since this process is lengthy and costly, computerized systems have been developed to predict virus resistance based on its genotype. The treating physician samples virus genotype sequences from the patient's blood and provides this data to a computerized system. The system then responds with drug recommendations.

Such systems are limited in accuracy, depending on the amount of data used for their creation, its quality and the richness of mathematical models used for the actual prediction. Prior to EuResist, such systems had several common characteristics that negatively impacted their accuracy: [3]

Purpose

The goal of EuResist was to develop a clinical decision support system for determining the most effective antiretroviral therapy for people diagnosed with HIV, based on clinical and virological data. [4] To do so required collecting a large database of in vivo data (clinical and genomic records of real treatments of HIV patients and their consequences), and using an array of prediction models instead of just one for improved prediction accuracy.

The database was created by merging local databases of various clinics across Europe. For each patient, it includes various personal and demographic details such as gender, age, country of origin, genomic sequencing of HIV found in the patient's blood, records of the drugs prescribed, and the changes in the amount of virus in the blood following these treatments.

This data was used to train an array of machine learning prediction models, among them Bayesian networks, logistic regression, and others. The model is accessed using a web interface allowing physicians to specify patients' clinical and genomic data. This data is sent to the prediction engines, and the combined response, which is displayed to the physician, includes various suggested treatments and a prediction of their effect on the amount of HIV in the blood.

The EuResist system was tested and compared with its predecessors by feeding it with historical data on patients for which treatment results are known. In one study in 2011 conducted by the British HIV Association, with a modest sample size of 15 treatment successes and 10 treatment failures, it was found that EuResist performed "comparably to or better than human experts". [5]

History

EuResist started in 2006 as a consortium funded by the European Union as part of the Virtual Physiological Human FP-6 framework. [4] The partners of this consortium were:

The consortium completed its commitment to the European Union in late 2008, at which time the EuResist system became available on line. The first five partners mentioned above continued to form a non-profit organization that maintains the system, expands the database with new clinical and genomical records and updates the prediction engines accordingly. As of mid-2010, an average of 600 queries are submitted to the EuResist system every quarter.

In 2010, it was reportedly the first decision support system of its kind to be available for free use online for customised highly active antiretroviral therapy for HIV. [6]

Awards

On June 1, 2009, EuResist received a Computerworld honors program laureate award, a global program honoring individuals and organizations that use information technology to benefit society. [7]

Related Research Articles

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

<span class="mw-page-title-main">Enfuvirtide</span> Chemical compound

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<span class="mw-page-title-main">Lamivudine</span> Chemical compound

Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.

<span class="mw-page-title-main">Indinavir</span> Chemical compound

Indinavir is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. The drug prevents protease from functioning normally. Consequently, HIV viruses cannot reproduce, causing a decrease in the viral load. Commercially sold indinavir is indinavir anhydrous, which is indinavir with an additional amine in the hydroxyethylene backbone. This enhances its solubility and oral bioavailability, making it easier for users to intake. It was synthetically produced for the purpose of inhibiting the protease in the HIV virus.

<span class="mw-page-title-main">Lamivudine/zidovudine</span> Combination drug for HIV

Lamivudine/zidovudine, sold under the brand name Combivir among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains two antiretroviral medications, lamivudine and zidovudine. It is used together with other antiretrovirals. It is taken by mouth twice a day.

Douglas D. Richman is an American infectious diseases physician and medical virologist. Richman's work has focused on the HIV/AIDS pandemic, since its appearance in the early 1980s. His major contributions have been in the areas of treatment, drug resistance, and pathogenicity.

Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) co-infection is a multi-faceted, chronic condition that significantly impacts public health. According to the World Health Organization (WHO), 2 to 15% of those infected with HIV are also affected by HCV, increasing their risk of morbidity and mortality due to accelerated liver disease. The burden of co-infection is especially high in certain high-risk groups, such as intravenous drug users and men who have sex with men. These individuals who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission including, but not limited to, exposure to HIV-positive blood, sexual intercourse, and passage of the Hepatitis C virus from mother to infant during childbirth.

<span class="mw-page-title-main">Elvitegravir</span> Chemical compound

Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

HIV Resistance Response Database Initiative (RDI) is a not-for-profit organisation established in 2002 which states its mission as "To improve the clinical management of HIV infection by developing a large clinical database and bioinformatic techniques that predict accurately any individual's response to any combination of HIV drugs."

HPTN 052 is the name of a clinical trial conducted in nine countries which examined whether starting people living with HIV on antiretroviral therapy (ART) can reduce the chance that they will pass HIV on to their sexual partners who do not have HIV. The trial showed remarkable success in preventing HIV transmission and were so compelling that the study's Data and Safety Monitoring Board (DSMB) asked the research team to share the results with all study participants and offer ART to the control group before the study ended. As a result of the study there was increased consensus that treatment as prevention should be included as a public health strategy in lowering HIV infection. The trial was organized by the HIV Prevention Trials Network (HPTN) and its chief architect was Myron S. Cohen.

The cost of HIV treatment is a complicated issue with an extremely wide range of costs due to varying factors such as the type of antiretroviral therapy and the country in which the treatment is administered. The first line therapy of HIV, or the initial antiretroviral drug regimen for an HIV-infected patient, is generally cheaper than subsequent second-line or third-line therapies. There is also a great variability of drug prices among low, middle, and high income countries. In general, low-income countries have the lowest cost of antiretroviral therapy, while middle- and high-income tend to have considerably higher costs. Certain prices of HIV drugs may be high and difficult to afford due to patent barriers on antiretroviral drugs and slow regulatory approval for drugs, which may lead to indirect consequences such as greater HIV drug resistance and an increased number of opportunistic infections. Government and activist movements have taken efforts to limit the price of HIV drugs.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Julio S. G. Montaner, is an Argentine-Canadian physician, professor and researcher. He is the director of the British Columbia Centre for Excellence in HIV/AIDS, the chair in AIDS Research and head of the Division of AIDS in the Faculty of Medicine at the University of British Columbia and the past-president of the International AIDS Society. He is also the director of the John Ruedy Immunodeficiency Clinic, and the Physician Program Director for HIV/AIDS PHC. He is known for his work on HAART, a role in the discovery of triple therapy as an effective treatment for HIV in the late 1990s, and a role in advocating the "Treatment as Prevention" Strategy in the mid-2000s, led by Myron Cohen of the HPTN 052 trial.

Deborah Persaud is a Guyanese-born American virologist who primarily works on HIV/AIDS at Johns Hopkins Children's Center.

<span class="mw-page-title-main">Fostemsavir</span> Chemical compound

Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.

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<span class="mw-page-title-main">Lenacapavir</span> Antiretroviral medication

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References

  1. ↑ Sharma, Deepak; Priyadarshini, Pragya; Vrati, Sudhanshu (2015-02-01). "Unraveling the Web of Viroinformatics: Computational Tools and Databases in Virus Research". Journal of Virology. 89 (3): 1489–1501. doi:10.1128/JVI.02027-14. ISSN   0022-538X. PMC   4300767 . PMID   25428870.
  2. ↑ Fischetti, Mark (June 2010). "Predictive Modeling Warns Drivers One Hour before Jams Occur". Scientific American. Retrieved 2020-10-01.
  3. ↑ Rosen-Zvi, Michal; Altmann, Andre; Prosperi, Mattia; Aharoni, Ehud; Neuvirth, Hani; Sönnerborg, Anders; Schülter, Eugen; Struck, Daniel; Peres, Yardena; Incardona, Francesca; Kaiser, Rolf; Zazzi, Maurizio; Lengauer, Thomas (1 July 2008). "Selecting anti-HIV therapies based on a variety of genomic and clinical factors". Bioinformatics. 24 (13): i399–i406. doi:10.1093/bioinformatics/btn141. PMC   2718619 . PMID   18586740 – via bioinformatics.oxfordjournals.org.
  4. 1 2 Rossetti, Barbara; Incardona, Francesca; Di Teodoro, Giulia; Mommo, Chiara; Saladini, Francesco; Kaiser, Rolf; Sönnerborg, Anders; Lengauer, Thomas; Zazzi, Maurizio; EuResist Network (2023-04-23). "Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network)". Tropical Medicine and Infectious Disease. 8 (5): 243. doi: 10.3390/tropicalmed8050243 . ISSN   2414-6366. PMC   10222321 . PMID   37235291.
  5. ↑ Zazzi, M.; Kaiser, R.; Sönnerborg, A.; Struck, D.; Altmann, A.; Prosperi, M.; Rosen-Zvi, M.; Petroczi, A.; Peres, Y.; Schülter, E.; Boucher, C. A.; Brun-Vezinet, F.; Harrigan, P. R.; Morris, L.; Obermeier, M. (April 2011). "Prediction of response to antiretroviral therapy by human experts and by the EuResist data-driven expert system (the EVE study)". HIV Medicine. 12 (4): 211–218. doi:10.1111/j.1468-1293.2010.00871.x. hdl: 2108/18679 . ISSN   1468-1293. PMID   20731728. S2CID   10360988.
  6. ↑ Pironti, A; Sönnerborg, A; Zazzi, M; Kaiser, R; Struck, D; Clotet, B; Vandamme, àM; Incardona, F; Lengauer, T; Rosen‐Zvi, M; Prosperi, M (November 2010). "The EuResist expert model for customised HAART optimisation: 2010 update and extension to newest compounds". Journal of the International AIDS Society. 13 (S4): O6. doi: 10.1186/1758-2652-13-S4-O6 . ISSN   1758-2652. PMC   3112868 .
  7. ↑ "Computerworld Honors Program - 2009 Finalists". www.cwhonors.org. Archived from the original on 2013-07-18. Retrieved 2010-08-25.


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