Prognosis of New Antiretroviral Drugs Efficacy based on Genome Analysis of HIV-1 Genetic Variants Dominating in Russia and Former USSR Countries
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
Ivanovsky Institute of Virology, Russia, Moscow
- National Center for Diseases Control, Georgia, Tbilisi
- University of Amsterdam / Academic Medical Center, The Netherlands, Amsterdam
Project summaryThe Project aim. The aim of the project is to predict the potential efficacy of the new antiretroviral drugs in vast majority of Russian and FSU countries patients infected with HIV variant possessing special genetic features.
The remote aim of the project will be the development of the common system for monitoring the HIV resistance mutations in Russia and the former Soviet Union republics.
Some new groups of drugs have been developed in recent years including inhibitors of HIV integrase, inhibitors of viral attachment and inhibitors of maturation. The information of the mutations to these drugs in B-subtype viruses was collected in developed countries and made a basis for the database on resistance mutations and their potential influence upon the drugs efficacy. This database contains very little information concerning the presence of these mutations in non-B variants and their potential susceptibility to the new drugs.
HIV variants circulating in Russia and FSU countries belong to subtype A HIV (about 92%). Of special interest is the fact of high genetic homogeneity of this variant among different geographical regions.
The genome analysis of HIV strains dominating in Russia and other countries HIV for the presence of drug resistance mutations prior to their wide use in Russia may allow many misinterpretations of genotyping results to be avoided once the therapy starts and finally will help to optimize therapy schemes for many patients.
The project’ influence on progress in this area. The project will be devoted to the study of the genetic polymorphism of HIV env, gag and pol genes in HIV and allows to characterize the mutations associated with drug resistance in HIV variants circulating in different geographic regions of Russia and FSU countries. The final conclusions will estimate the association between the presence of mutations and their potential influence upon the susceptibility to the new drugs.
The participants’ expertise. The scientists taking part in the project have considerable experience in HIV molecular epidemiology proved by their publications and participation in the international conferences and projects. The other institutions involved have positive results and tested methodology of HIV studies.
Expected results and their application. The results obtained in this study may form a basis for strategy of anti-HIV drugs use and purchase in Russia and in bordering countries having the same molecular epidemiology landscapes. Furthermore, the data concerning the susceptibility of all the particular patterns of mutations to different drugs may be useful for developing improved versions of drugs and their combinations.
Meeting the ISTC goals and objectives. Since former “weapons” scientists will take part in this Project implementation and because it is exceptionally peaceful the Project meets the ISTC goals. Obtaining new data on genetic subtypes circulating on the territory of Russia and the countries of the former USSR and their potential drug resistance will contribute to the improvement of the control over HIV-infection. Adherence to these objectives can be attained by planned wide involvement of scientists and participating institutions into international scientific community through providing information on the Project during international conferences and workshops.
Scope of activities. The project activities will include:
- blood sample collecting and DNA preparation at the sites (in the course of the project);
- transporting of the samples to Moscow and Tbilisi (in the course of the project);
- genotyping and analysis of HIV resistance mutations in the reference laboratories (Ivanovsky Institute of Virology, laboratory of T-lymphotropic viruses, Moscow and National Center for Disease Control and Public Health, Tbilisi) (in the course of the project);
- developing of practical recommendations and preparing the letter for the Russian and Georgian Ministries of health concerning the potential efficacy of the new drugs.
Role of Foreign Collaborators/Partners. The well-known scientist Dr V.Lukashov (University of Amsterdam) expressed his wish to become a Collaborator on this Project. Dr Lukashov will take part in the development of databases of resistance mutations, their submitting to the international databases and phylogenetic analysis. The plans of the work will be discussed with the collaborator, the results of the studies will be published in the international and Russian scientific journals. The HIV-1 RNA and DNA sequences analyzed will be sent to the international viral gene data banks and opened for the international access.
Technical approach and methodology. All HIV-positive persons will be assigned to the study after obtaining of the written informed consent under approved human use protocols according to the form approved by Ethical Committee.
The collection of blood cells and plasma will be carried out employing the conventional procedure. All disposable materials, instruments and auxiliary equipment will be stocked up and delivered to the laboratories at the beginning of the period of the fulfillment of project.
Collecting will be carried out during entire period of the fulfillment of the project; the transportation of the obtained samples to Moscow or Tbilisi will be organized periodically as the collections form.
The procedure of the transporting samples of the potentially infectious material will attract the special mail service (for example, World Courier) under the special conditions (vacuum flasks with ice, airtight packing, special marking).
The main methods include amplification of gag, pol and env genes of HIV-1 proviral DNA or viral RNA and subsequent genotyping with sequence analysis. The sequencing of HIV-1 proviral DNA and RNA will be used for drug resistance analysis as well.
The phylogenetic analysis of nucleotide sequences and search for the potential resistance mutations will be carried based on the application of the specialized computer programs and Internet resources.