Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria.

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

doi:10.3390/v13010116

Abstract

HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.

Highlights

HIV-1 group M is responsible for the current pandemic and comprises 10 distinct subtypes (A, B, C, D, F, G, H, J, K, and L), at least 102 different circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs) [5]
We found that CRF01_AE infections grew into a large sub-epidemic among persons who inject drugs (PWID), after it was first introduced into Bulgaria, most likely from Vietnam, with some onward transmission to other European countries
CRF01_AE has become the second most predominant subtype in Bulgaria, which to our knowledge represents the highest share of CRF01_AE in Europe [5,9]. Our results resemble those described for other HIV-1 outbreaks in PWID in multiple countries, including Greece, Luxembourg, and resulting from the opioid crisis in the United States with the introduction of specific subtypes into this vulnerable population followed by rapid dissemination [16,31,35,36]

Summary

Introduction

HIV-1 group M is responsible for the current pandemic and comprises 10 distinct subtypes (A, B, C, D, F, G, H, J, K, and L), at least 102 different circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs) [5]. CRFs accounted for 16.7% of all HIV-1 infections between 2010 and 2015 and are most common in places where different subtypes co-circulate [5]. Of these CRFs, CRF01_AE has the largest global prevalence comprising 5.3% of all HIV-1 infections [5]

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