Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria.

Ivailo Alexiev,Carole Seguin-Devaux,Anna Gancheva,Lyubomira Grigorova,Aleksandra Partsuneva,William M Switzer,Sergey Knyazev,Asya Kostadinova,Yi Pan,Ellsworth M Campbell,Reneta Dimitrova

doi:10.3390/v12040441

Abstract

HIV-1 subtype B is the predominant strain in Bulgaria, yet little is known about the molecular epidemiology of these infections, including its origin and transmissibility. We used a phylodynamics approach by combining and analyzing 663 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1988–2018 and associated epidemiologic data to better understand this sub-epidemic in Bulgaria. Using network analyses at a 1.5% genetic distance threshold (d) we found several large phylogenetic clusters composed mostly of men who have sex with men (MSM) and male heterosexuals (HET). However, at d = 0.5%, used to identify more recent transmission, the largest clusters dissociated to become smaller in size. The majority of female HET and persons with other transmission risks were singletons or pairs in the network. Phylogenetic analysis of the Bulgarian pol sequences with publicly available global sequences showed that subtype B was likely introduced into Bulgaria from multiple countries, including Israel and several European countries. Our findings indicate that subtype B was introduced into Bulgaria multiple times since 1988 and then infections rapidly spread among MSM and non-disclosed MSM. These high-risk behaviors continue to spread subtype B infection in Bulgaria as evidenced by the large clusters at d = 0.5%. Relatively low levels of antiretroviral drug resistance were observed in our study. Prevention strategies should continue to include increased testing and linkage to care and treatment, as well as expanded outreach to the MSM communities.

Highlights

HIV-1 consists of four major phylogenetic groups: M, N, O, and P, representing independent cross-species transition from SIV in chimpanzee and gorillas to HIV in humans [1]
We found that participants with subtype B infection had lower percentages of heterosexual (38.6% vs 44.6%) transmissions compared to non-subtype B participants, higher percentages of men who have sex with men (MSM) (56.7% vs. 20.3%) compared to non-subtype B participants, and much lower percentages of PWIDS (3.3% vs. 30.9%) compared to non-subtype B participants (Table 1)
The first case of subtype B infection in Bulgaria was diagnosed in a person who received a blood transfusion, subsequent diagnoses were mostly heterosexual transmission cases until 2006 when more diagnoses were found in MSM [14]

Summary

Introduction

HIV-1 consists of four major phylogenetic groups: M (major), N (new), O (outlier), and P, representing independent cross-species transition from SIV in chimpanzee and gorillas to HIV in humans [1]. HIV-1 group M is responsible for the current pandemic and comprises genetically distinct subtypes (A, B, C, D, F, G, H, J, K, and, more recently, L), 101 circulating recombinant forms (CRFs) to date, and numerous unique recombinant forms (URFs) [2,3]. HIV-1 subtypes are unequally distributed globally, which has been explained by different founder effects followed by local spread driven by socioeconomic and behavioral factors and circulation within and between specific risk groups [4,5,6]. CRFs and URFs are widely distributed in central Africa and in countries where different subtypes co-circulate [2,8,9]. The wide variety of subtypes, which are distributed mainly in different populations, may be used for molecular epidemiological analysis to track and understand the dynamics and patterns of HIV-1 transmission and for developing strategic prevention programs [10]

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Conclusion