• Lyubomira Grigorova NCIPD Author
  • Reneta Dimitrova Author https://orcid.org/0000-0001-7711-6798
  • Aleksandra Partsuneva Author
  • Anna Gancheva Author
  • Asya Kostadinova Author
  • Ivaylo Elenkov Author
  • Nina Yancheva Author
  • Mariyana Stoycheva Author
  • Tsetsa Doychinova Author
  • Liliya Pekova Author
  • Minas Kosmidis Author
  • Ivailo Alexiev Author https://orcid.org/0000-0002-3186-1124




HIV-1, CRF01_AE, drug resistance, transmission clusters


Background. In Bulgaria the second most predominant HIV-1 strain after subtype B is CRF01_AE.

Material and Methods. 270 HIV-1 polymerase (pol) CRF01_AE sequences collected between 1995–2019 were analyzed with the phylogenetic approach. To identify transmission clusters, we used two different genetic distance thresholds (d), i. e. 1.5% and 0.5%.

Results. Genetic distance d=1.5% defined more distant infections in a huge cluster of 154 sequences composed mostly of people, who inject drugs (PWID), whereas when (d) was reduced to 0.5%, we determined more recent transmissions and the large cluster disintegrated into smaller ones. Different drug resistance mutations (DRM) were detected in patient’s HIV-1 pol sequences and were most common in male heterosexual (HET) single sequences.

Conclusions. Our data showed repeated introduction of CRF01_AE in Bulgaria and rapid spread of the infection among PWID groups. Molecular monitoring of the epidemic among PWID communities could help reduce the spread of HIV-1 infection.


Download data is not yet available.


Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. doi: 10.1101/cshperspect.a006841. PMID: 22229120; PMCID: PMC3234451. DOI: https://doi.org/10.1101/cshperspect.a006841

Hemelaar J. The origin and diversity of the HIV-1 pandemic. Trends Mol Med. 2012 Mar;18(3):182-92. doi: 10.1016/j.molmed.2011.12.001. Epub 2012 Jan 11. PMID: 22240486. DOI: https://doi.org/10.1016/j.molmed.2011.12.001

Raymond S, Delobel P, Rogez S, et al. Genotypic prediction of HIV-1 CRF01_AE tropism. J Clin Microbiol. 2013;51(2):564-570. doi:10.1128/JCM.02328-12 DOI: https://doi.org/10.1128/JCM.02328-12

Abecasis A. 2008. Demographic determinants of HIV-1 subtype distribution in Europe. Sixth Eur. HIV Drug Resist. Workshop, Budapest, Hungary http://www.hivpresentation.com/assets/0E533013-423A-F6F7-C45CBE252EB509AD.PDF (Google Scholar)

Stanojevic, M., Alexiev, I. Beshkov, D., Gokengin, D., Mezei, M., Minarovits, J., Otelea, D., Paraschiv, S., Poljak, M., Zidovec S.L., et al. HIV1 Molecular Epidemiology in the Balkans - A Melting Pot for High Genetic Diversity. Aids. Rev. 2012, 14:28-36.

Alexiev, I., Beshkov, D., Shankar, A., Hanson, D.L., Paraskevis, D., Georgieva, V., Karamacheva, L., Taskov, H., Varleva, T., Elenkov, I., et al. Detailed molecular epidemiologic characterization of HIV-1 infection in Bulgaria reveals broad diversity and evolving phylodynamics. PLoS ONE 2013, 8, e59666. DOI: https://doi.org/10.1371/journal.pone.0059666

Alexiev, I., Shankar, A., Wensing, A.M.J., Beshkov, D., Elenkov, I., Stoycheva, M., Nikolova, D., Nikolova, M., Switzer W.M. Low HIV-1 transmitted drug resistance in Bulgaria against a background of high clade diversity. J. Antimicrob. Chemoth. 2015, 70.6: 1874-1880. DOI: https://doi.org/10.1093/jac/dkv011

Alexiev, I., Shankar, A., Dimitrova, R., Gancheva, A., Kostadinova, A., Teoharov, P., Golkocheva, E., Nikolova, M., Muhtarova, M., Elenkov, I., et al. Origin and spread of HIV-1 in persons who inject drugs in Bulgaria. Infect. Genet. Evol. 2016, 46, 269–278. DOI: https://doi.org/10.1016/j.meegid.2016.05.029

Larsson, A. AliView: A fast and lightweight alignment viewer and editor for large data sets. Bioinformatics 2014, 30, 3276–3278. DOI: https://doi.org/10.1093/bioinformatics/btu531

Lole, K.S., Bollinger, R.C., Paranjape, R.S., Gadkari, D., Kulkarni, S.S., Novak, N.G., Ingersoll, R., Sheppard, H.W.; Ray, S.C. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol. 1999 Jan;73(1):152-60. DOI: https://doi.org/10.1128/JVI.73.1.152-160.1999

Price, M., Dehal, P., Arkin, A. FastTree 2–approximately maximum-likelihood trees for large alignments. PloS ONE. 2010, Mar 10;5(3):e9490. DOI: https://doi.org/10.1371/journal.pone.0009490

Hadfield, J., Megill, C., Bell, S.M., Huddleston, J., Potter, B., Callender, C., Sagulenko, P., Bedford, T., Neher, R.A. Nextstrain: real-time tracking of pathogen evolution. Bioinformatics. 2018, Dec 1;34(23):4121-3. DOI: https://doi.org/10.1093/bioinformatics/bty407

Katoh, K., Rozewicki, J., Yamada KD. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Briefings in bioinformatics. 2019 Jul;20(4):1160-6. DOI: https://doi.org/10.1093/bib/bbx108

Kuraku, S., Zmasek, C.M., Nishimura, O., Katoh, K. aLeaves facilitates on-demand exploration of metazoan gene family trees on MAFFT sequence alignment server with enhanced interactivity. Nucleic Acids Res. 2013 Jul 1;41(W1):W22-8. DOI: https://doi.org/10.1093/nar/gkt389

Sagulenko, P., Puller, V., Neher, R.A. TreeTime: Maximum-likelihood phylodynamic analysis. Virus Evol. 2018 Jan;4(1):vex042. DOI: https://doi.org/10.1093/ve/vex042

Machnowska, P., Meixenberger, K., Schmidt, D., Jessen, H., Hillenbrand, H., Gunsenheimer-Bartmeyer, B., et al. Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort. PLoS ONE. 2019, Mar 3;14(1): e0209605. DOI: https://doi.org/10.1371/journal.pone.0209605

Alexiev, I., M. Campbell, E., Knyazev, S., Pan, Y., Grigorova, L., Dimitrova, R., Partsuneva, A., Gancheva, A., Kostadinova, A., Seguin-Devaux, C., M. Switzer, W.M. Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria. Viruses 2020, 12, 441. DOI: https://doi.org/10.3390/v12040441

Ivailo Alexiev, Elitsa Golkocheva-Markova, Asya Kostadinova, Reneta Dimitrova, Lora Nikolova, Anna Gancheva, Tencho Tenev, Ivaylo Elenkov, Tatiana Tcherveniakova, Nina Yancheva, Mariyana Stoycheva, Tsetsa Doychinova, Lilia Pekova, Marina Alexandrova, Andon Timchev, Dimitar Strashimirov, Maria Nikolova. The prevalence of hepatitis B and C co-infections among people with HIV-1 in Bulgaria: 2010–2015. Future Virology, 2019, 14(12), 791-798. DOI: https://doi.org/10.2217/fvl-2019-0092

Ivailo Alexiev, Danail Beshkov, Ivaylo Elenkov, Mariana Stoicheva, Daniela Nikolova. Molecular Epidemiology Surveillance of Pure HIV-1 Subtypes in Bulgaria. Problems of Infectious and Parasitic Diseases, 2013, 41 (1).

Ivailo Alexiev, Reneta Dimitrova, Anna Gancheva, Asia Kostadinova, Ivaylo Elenkov, Mariyana Stoycheva, Daniela Nikolova, Maria Nikolova Danail Beshkov. HIV-1 Transmitted Drug Resistance in Bulgaria. Problems of Infectious and Parasitic Diseases, 2015, 43 (1).

Ivailo Alexiev, Danail Beshkov, Ivaylo Elenkov, Mariana Stoicheva, Daniela Nikolova. Molecular Epidemiology Surveillance of HIV-1 CRFs and URFs in Bulgaria. Problems of Infectious and Parasitic Diseases, 2013, 41 (1).







How to Cite

Grigorova, L.; Dimitrova, R.; Partsuneva, A.; Gancheva, A.; Kostadinova, A.; Elenkov, I.; Yancheva, N.; Stoycheva, M.; Doychinova, T.; Pekova, L.; Kosmidis, M.; Alexiev, I. DRUG RESISTANCE MUTATIONS AND TRANSMISSION CLUSTERS OF THE HIV-1 CRF01_AE SUB-EPIDEMIC IN BULGARIA. Probl Infect Parasit Dis 2022, 49 (3), 12-19. https://doi.org/10.58395/pipd.v49i3.68.

Most read articles by the same author(s)

1 2 > >>