STUDY OF BIOLOGICAL PROPERTIES OF HIV-1 VARIANTS RESISTANT TO ANTIRETROVIRALPREPARATIONS

Aim. Separation of HIV-1 isolates from HIV infected patients who had received antiretroviral therapy
courses. Analysis of genetic and replicative properties of the separated isolates, study of pol gene mutation
stability sustentation that is responsible for the emergence of drug resistance. Materials and methods. HIV
isolate separation was carried out by co-cultivation of peripheral blood mononuclears of HIV infected patients
with previously stimulated phytohemagglutinin cells of healthy donors. Virus replication was evaluated by
the level of p24 virus specific protein accumulation determined in enzyme immunoassay. HIV-1 subtype
identification, detection of HIV-1 genome mutations were carried out by pol gene nucleotide sequence determination
and subsequent analysis of the data obtained - by using specialized program resources. Results.
14 infectious HIV-1 subtype A, B and CRF02_AG isolates were separated containing various sets of mutations
determining resistance to widely used in clinical practice nucleoside and non-nucleoside reverse transcriptase
inhibitors. Comparative analysis of mutation specter detected in HIV-1 variant genomes before
isolation and after their cultivation showed that during HIV-1 cultivation in mononuclear blood cells without
the addition of antiretroviral preparations not only partial loss of mutations is observed but also emergence
of new drug resistance mutations; and most of the mutation causing virus resistance to antiretroviral preparations
remain. Conclusion. High reproductive properties of the HIV-1 isolates separated allow to use them
to evaluate effectiveness of the drugs being developed against HIV-1 resistant to antiretroviral preparations.

HIV-1, HIV-1 replicative properties, resistance to antiretroviral preparations, Novosibirsk region