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

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.

Phylodynamic analysis reveals changing transmission dynamics of HIV-1 CRF01_AE in Japan from heterosexuals to men who have sex with men

“…This finding was consistent with a previous study from Australia, which is in the same Western Pacific region (Di Giallonardo et al, 2021). However, at the time of our study, it was not applicable to the European region, where heterosexuals still dominate the transmission network of CRF01_AE (Alexiev et al, 2021;Esbjornsson et al, 2016). Careful attention should be paid to transmission trend of CRF01_AE because a similar change in predominant risk group could occur in other regions.…”

Molecular Analysis of Dihydropteroate Synthase Gene Mutations in Pneumocystis jirovecii Isolates among Bulgarian Patients with Pneumocystis Pneumonia

“…Other point mutations such as those at codons 23, 60, and 111 of the P. jirovecii DHPS locus were also suspected to be involved in drug resistance (sulpha/sulphone) [36,47,87,88]. In our study, aside from the most commonly described point mutations at codons 55 and 57, the presence of sequence variations at other studied DHPS codons (23,60,75,78,83,88, 100, and 111) was examined. No mutations were detected in all Bulgarian P. jirovecii isolate sequences.…”

“…In Bulgaria, since the beginning of the HIV/AIDS epidemic (1986) until 2021, 3721 individuals were diagnosed with HIV [59,60]. A total of 1950 persons were hospitalised for treatment of HIV infection or were subsequently followed up in 2021.…”

Incorporating metadata in HIV transmission network reconstruction: A machine learning feasibility assessment

“…The metadata (epidemiologic, serologic, behavioral, risk partners) of the individuals in the molecular network have been effectively analyzed to track the origin of foregoing outbreaks and to evaluate transmission dynamics [12][13][14] for acute and unreported HIV transmissions and to design potent prevention intervention strategies [15,16]. These findings reveal the importance of information inherent in the metadata associated with the molecular network.…”