Molecular Epidemiology of HIV-1 in Eastern Europe and Russia

Abstract

The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.

Keywords: Eastern Europe; HIV-1 sub-subtype A6; epidemiology; phylogeny; pre-existing drug resistance mutations; unique recombinant forms.

Figure 1

Sequence analysis of the HIV-1 pol gene. (A): Unrooted phylogenetic analysis. Colours were assigned based on sequence analysis using HIV COMET, the Stanford database tool, and the REGA tool. HIV-1 subtype A1, A2, A, B, D, and G reference sequences were included. (B): Distribution of HIV-1 subtypes, sub-subtypes, and recombinant forms in the different countries and regions studied. CRF: Circulating recombinant form. URF: Unique recombinant form. Other: Subtype D (1 case), CRF03_AB (2 cases), and G (6 cases). (C): Phylogeny of HIV-1 subtype B viruses identified in this study. The tree was rooted on a genotype C sequence (C.U52953). The numbers indicate the genetic distance (divergence) between the viruses. (D): Phylogenetic analysis of CRF02_AG and CRF63_02A6 viruses. The tree was rooted on a subtype C sequence (C.U52953). The samples in grey were conclusively assigned CRF02_AG (MOS84704 and MOS614571) or CRF063_02A6 (MOS614752) based on the phylogenetic analysis.

Figure 2

(A): Phylogenetic relation between the HIV-1 strains coloured by the locations where the viruses were obtained. The central cluster are the subtype B sequences; the small, Moscow-based cluster between this cluster and the main cluster are the genotype G sequences. The big cluster on the outside are the sub-subtype A6 sequences. The numbers indicate the genetic distance (divergence) between the viruses. The tree was rooted on a subtype D sequence (D.K0345). (B): The most likely transmission routes were inferred from the phylogenetic analysis depicted in panel A using the nextstrain workflow. Directionality of transmissions is pictured by the connecting lines, which have the colour of the country from which the transmissions took place. The surface area of the circles represents the number of cases analysed in each region. (C): Subtype distribution by transmission route. For transmission route categories see Table 3 legend.