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

Abstract

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 (MutV77I/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 MutV77I/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.