Nosik M.N.1, Ryzhov A.K.1, Kravtchenko A.V.2

1- I.I. Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia
       2- Central Research Institute of Epidemiology Ministry of Health, Moscow, Russia

 

GENETIC ANALYSIS OF HIV-VARIANTS IN UNTREATED HIV-INFECTED  INDIVIDUALS  FROM MOSCOW REGION, RUSSIA.

 

A problem of HIV-infection is one of the most pressing public health issues worldwide. The Eastern Europe in particularly has seen a steady increase in HIV infections since 2000.  Nearly 90% cases of HIV-infection are largely due to Russian Federation and Ukraine.  At the present time there are 665. 590 officially registered cases of HIV-infection in Russia. However, this figure significantly underestimates the actual number of HIV-infected individuals. According to WHO on one registered case of HIV-infection there are several unregistered cases. In about 8-10 years there will be one more serious problem – hundreds of thousands of HIV-infected individuals will have the terminal stage of infection – AIDS. This means that there will be a big number of young disabled people. As a consequence this problem from medical issue will become a social issue. With access to the Highly Active Antiretroviral Therapy (HAART) which allows suppressing virus replication the number of lethal cases and the number of different complications among HIV-infected individuals significantly decreased. But unfortunately this is a temporal success. Due to its complex structure the human immunodeficiency virus can adapt to the drugs and thus can neutralize the positive effect of antiviral therapy. As access to HAART increases the emerging of HIV drug resistant strains is also increases. The multiple resistance to the drugs of different classes affects the success of antiviral therapy. The number of reported cases of transmission of HIV- drug resistant strains to the HIV-infected individuals who were not undergoing HAART and as result the failure of the therapy is increasing.  More over the existing mutations in the HIV-genome which are responsible for resistance to antiretroviral drugs due to the natural polymorphism of the viral quasispecies may minimize the positive effect of antiretroviral drugs prior to the onset of therapy.  Thus   the therapy failed among 16-27% drug-naïve HIV-infected individuals and among 50-70% patients who were undergoing treatment.  The goal of the work was to analyze the rate of emergency of the drug-resistant HIV-variants among drug-naïve patients from Moscow Region where access to antiretroviral therapy is rather high.

Over the period of 2010-2011 blood samples were collected from 110 HIV-infected individuals who did not receive antiviral therapy. All individuals were living in the Moscow Region: Moscow City (n=58) and Moscow District (n=52).  The fragment of pol-gene encoding the fragment’s of protease- (PR) and reverse transcriptase- (RT) genes with most studied drug-resistant mutations was analyzed.

For its analysis HIV primers specifically suitable for studying the HIV-variants circulating in the territory of Russia were calculated and designed (CCAAAGGTTAAACAATGGC and TTTAGATTCTTAAATGGCTCC).  HIV Drug Resistance Database was used for the analysis of HIV- mutations.  The minor mutations associated with the drug resistance to protease inhibitors were: L10I (10%) and a common polymorphism mutation V77I (9,1%). For the RT gene polymorphic mutation V90I was detected also in 9,1% cases. The K103R mutation which usually occurs in about 1-2% of untreated individuals was detected in 1,8%. The detected occurrence rate of mutation A62V in reverse RT gene (characteristic for subtype A) was 39,1%. Only in one sample (0,9%) the M184V mutation which causes high level resistance to lamivudine (3TC) and to Emtriva (FTC) was detected. A polymorphic mutation E138A was detected in 0,9% cases. This mutation is associated with decreased ETR (End of Treatment response) against etravirine.

Thus the prevalence of resistant mutations among drug-naïve patients is rather low. This fact indicates that in the Moscow Region in spite of high availability to HAART the prevalence of HIV- isolates resistant to antiretroviral drugs is still not very high.  However considering the long lasting antiviral therapy and emerging of new generation drugs   the constant monitoring is necessary over the circulation of drug-resistant strains.

 

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