Human Immunodeficiency Virus-1 Diversity in the Moscow Region, Russia: Phylodynamics of the Most Common Subtypes

Abstract

This study analyzes the HIV-1 subtype diversity and its phylodynamics in Moscow region, which is the most densely populated area of Russia characterized by high rates of internal and external migration. The demographic and viral data from 896 HIV-infected individuals collected during 2011-2016 were analyzed. The study revealed broad diversity in the HIV-1 subtypes found in Moscow, which included A6 (85.1%), B (7.6%), CRF02_AG (1.2%) and URF_A6/B recombinants (4.2%). Other HIV-1 subtypes were detected as single cases. While A6 was most prevalent (>86.0%) among heterosexuals, injecting drug users and cases of mother-to-child transmission of HIV, subtype B (76.3%) was more common in men who have sex with men. Phylogenetic reconstruction revealed that the A6 sequences were introduced into the epidemic cluster that arose approximately around 1998. Within the subtype B, six major epidemic clusters were identified, each of which contained strains associated with only one or two dominant transmission routes. The date of origin of these clusters varied between 1980 and 1993, indicating that the HIV-1 B epidemic began much earlier than the HIV-1 A6 epidemic. Reconstruction of the demographic history of subtypes A6 and B identified at least two epidemic growth phases, which included an initial phase of exponential growth followed by a decline in the mid/late 2010s. Thus, our results indicate an increase in HIV-1 genetic diversity in Moscow region. They also help in understanding the HIV-1 temporal dynamics as well as the genetic relationships between its circulating strains.

Keywords: HIV-1 subtypes; Moscow region; Russia; TMRCA; diversity; epidemic; phylodynamics; transmission route.

Figure 1

Maximum-likelihood phylogenetic tree of 896 HIV-1 pol sequences from HIV-infected individuals in Moscow region, from 2011 to 2016. The presented tree describes the analysis of all dataset, where the subtype A6 and B clades of HIV-1 are presented in a condensed form. The topology of the A6-clade and B-clade are presented separately (see Supplemental Figure 1). Branches are colored according to the HIV-1 subtypes as indicated in the legend. Support values (BS/SH-aLRT) are shown for the key nodes. Asterisks point to locations of unique recombination forms (URFs; see main text). The reference sequence for each subtype was selected using the Reference Alignment from Rega HIV-1 Subtyping Tool and marked by a circle.

Figure 2

Maximum-likelihood phylogeny and phylodynamic analysis of HIV-1 subtypes in Moscow region. Shown is the analysis of subtypes A6 (left; A,C,E) and B (right; B,D,F). (A,B) ML-tree of the HIV-1 subtypes A and B pol sequences from HIV-infected persons in Moscow, 2007–2016. The colored areas indicate the positions of major epidemic clusters (sub-clusters) identified in the region. Branches are colored according to the risk factor of infection as indicated in the legends. Support values (BS/SH-aLRT) are shown for the key nodes. The trees were rooted through African A1 and D sequences (for A6 and B subtype, respectively). (C,D) Bayesian estimates of times of the most recent common ancestors (TMRCA) for the major epidemic clusters (sub-clusters) by BEAST analysis. Points represent the median value, solid lines - 95% credible intervals. (E,F) Bayesian skyline plot (BSP) showing effective number of infections over time Ne(t). Estimates of the Ne(t) are presented as median (solid blue line) with the corresponding 95% HPD credibility interval (blue area).