In the present work, a total of 132 HIV-1 env gene C2-V3-C3 sequences belonging to the IDU-A genetic variant were analyzed. The variants were obtained from the viruses circulating among IDUs and heterosexuals in the Perm region at different periods. It was shown that the rate of the divergence of the IDU-A HIV-1 viruses from a common ancestor increased 4.3 times (p < 0.001) in 2011 as compared with the onset of the epidemics. The rate of the HIV-1 evolution was different in the two risk groups of the infection. The mean genetic distance of HIV-1 variants circulating among heterosexuals was 1.3 times longer (p = 0.008) than that among IDUs. The accumulation rate of the nucleotide (including nonsynonymous) substitutions in the C2-V3-C3 HIV-1 env gene region among individuals infected by heterosexual contacts was 1.7 times higher than that among IDUs. The differences in the positions of the codons subjected to positive selection were demonstrated depending on the infection risk group tested.