Polymorphism of the Genome Region Coding for Protease and Reverse Transcriptase in HIV Type 1 Subtype A Variants Prevailing in CIS Countries

摘要

The pol nucleotide sequences coding for protease and reverse transcriptase were examined to study the frequency of drug resistance mutations in HIV-1 subtype A in Russia.The sample included 141 HIV-infected subjects who had never received antiretroviral drugs before.Primary resistance mutations occurred at a low (less than 1 %) frequency,while unusually high frequencies were observed for the secondary mutations causing substitutions V77I in protease (67%) and A62V in reverse transcriptase (63%).The V77I and A62V mutations were associated in most cases.HIV-1 isolates carrying both mutations (Mut_(V77I/A62V)) had several synonymous substitutions in pol,which was indicative of their common origin.Examination of a larger sample of HIV-1 isolates (N=319) by hybridization with biological microchips and by restriction enzyme analysis showed that the Mut_(V77I/A62V) variant dominated in Russia in terms of both frequency (56%) and geographic distribution,prevailing in regions with the highest incidence of HIV-1 infection (e.g.,Irkutsk,Samara,and Moscow regions).In addition,analysis revealed the genotypes that contained none of the V77I and A62V mutations or only one of them.The evolutionary relationships of the four HIV-1 variants-and the role of pol gene polymorphism in replicative activity and drug resistance of HIV-1 are discussed.