The use of computational models to predict response to HIV therapy for clinical cases in Romania.

نویسندگان

  • Andrew D Revell
  • Luminiţa Ene
  • Dan Duiculescu
  • Dechao Wang
  • Mike Youle
  • Anton Pozniak
  • Julio Montaner
  • Brendan A Larder
چکیده

INTRODUCTION A major challenge in Romania is the optimisation of antiretroviral therapy for the many HIV-infected adults with, on average, a decade of treatment experience. The RDI has developed computational models that predict virological response to therapy but these require a genotype, which is not routinely available in Romania. Moreover the models, which were trained without any Romanian data, have proved most accurate for patients from the healthcare settings that contributed the training data. Here we develop and test a novel model that does not require a genotype, with test data from Romania. METHODS A random forest (RF) model was developed to predict the probability of the HIV viral load (VL) being reduced to <50 copies/ml following therapy change. The input variables were baseline VL, CD4 count, treatment history and time to follow-up. The model was developed with 3188 treatment changes episodes (TCEs) from North America, Western Europe and Australia. The model's predictions for 100 independent TCEs from the RDI database were compared to those of a model trained with the same data plus genotypes and then tested using 39 TCEs from Romania in terms of the area under the ROC curve (AUC). RESULTS When tested with the 100 independent RDI TCEs, the AUC values for the models with and without genotypes were 0.88 and 0.86 respectively. For the 39 Romanian TCEs the AUC was 0.60. However, when 14 cases with viral loads that may have been between 50 and 400 copies were removed, the AUC increased to 0.83. DISCUSSION Despite having been trained without data from Romania, the model predicted treatment responses in treatment-experienced Romanian patients with clade F virus accurately without the need for a genotype. The results suggest that this approach might be generalisable and useful in helping design optimal salvage regimens for treatment-experienced patients in countries with limited resources where genotyping is not always available.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The response of Geant4 hadronic models to the study of neutrons produced in proton irradiation to the light materials

Neutron is one of the products of the interaction of high energy protons with light nuclei. Using computational Monte Carlo codes, it is possible to calculate and predict the neutron spectrum, neutron flux, and doses by simulating the system. But the use of different hadronic models in this process can influence the results of these calculations. In this research, the response of the four hadro...

متن کامل

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings.

OBJECTIVES Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs....

متن کامل

Immune Response to Standard Hepatitis B Vaccination in HIV-Infected Patients

Background: Due to their similar routes of transmission, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection occurs considerably. HBV infection progresses more rapidly in HIV-infected patients. Therefore, HBV vaccination of all non-immune HIV infected patients is recommended. On the other hand, HIV-infected subjects have suboptimal responses to HBV vaccine. In this study...

متن کامل

A QSAR Study of HIV Protease Inhibitors Using Computational Descriptors to Prediction of pki of Cycle Derivatives of Urea

Preventing and reducing the spread of HIV (HIV) has always been a concern in medical science. One of the most common ways to control the virus is using enzyme-blocking drugs. In this study, we attempted to predict the biological activity (PKi) of organic urea derivatives in protease inhibitor compounds using molecular modeling using QSAR (Quantitative Structure Activity Relation), which is the ...

متن کامل

Modelling of Suddenly Expanded Flow Process in Supersonic Mach Regime using Design of Experiments and Response Surface Methodology

The present work is an attempt to model, analyze, and control the flow at the base of an abruptly expanded circular duct by using design of experiments (DOE) and response surface methodology (RSM). Tiny-jets in the form of orifice were positioned at an interval of 900, 6.5 mm from the primary axis of the main jet of the nozzle. Experiments were conducted to measure two responses namely, base pr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Germs

دوره 2 1  شماره 

صفحات  -

تاریخ انتشار 2012