HIV‐1 resistance to antiretroviral drugs among infected residents of Altai Krai with antiretroviral therapy failure

Aim. The objective was to assess the development of HIV‐1 resistance in patients with virological failure of antiretroviral therapy. 

Resistance analysis of HIV‐1 and clinico‐epidemiological data was performed for 367 infected residents of Altai Krai. Nucleotide sequences of HIV‐1 protease and reverse transcriptase were obtained by PCR and sequencing of viral genome regions. Genotyping, phylogenetic, and mutation analyses were performed using specialised resources.

In the sample studied, a predominance of HIV‐1 CRF63_02A6 (52.0 %) and subtype A6 (42.5 %) was detected. Drug resistance of HIV‐1 was found in 310 (84.5 %) of 367 samples. The most commonly used NRTI combination was TDF+3TC (60.8 %). The prevalence of HIV‐1 resistance to TDF was

46.9 % and to 3TC was 86.6 %. Drugs of the NNRTI group were taken by 51.5 % of persons; EFV was included in 38.1 % of prescribed regimens and the prevalence of viral resistance to EFV was 87.9 %. Protease inhibitors were taken by 25.8 % of patients; combinations LPV+RPV (36.8 %) and ATV+RPV (43.2 %) were more frequently prescribed. The prevalence of HIV‐1 resistance to LPV+RPV was 33.3 % and to ATV+RPV was 35.9 %. The most frequent resistance mutations among HIV were: to NRTIs – M184V/I (62.2 %), K65R/E (17.5 %); to NNRTIs – K103N/S (47.8 %), E138G/A/K/Q (23.7 %); to PIs – V82A/G and M46I/L (20.5 % each).

The study underscores the importance of access to HIV‐1 resistance testing, since timely detection of resistant viral strains and appropriate adjustment of therapy can restore treatment effectiveness, prevent the emergence of new mutations and limit the development of crossresistance to other ARVs.

1. UNIIDS (2024) Global AIDS Update 2024.Geneva. Available at: https://www.unaids.org/ru/resources/fact‐sheet

2. Garland J.M., Mayan H., Kantor R. Treatment of Advanced HIV in the Modern Era. Drugs, 2025, vol. 85, no. 7, pp. 883–909. https://doi.org/10.1007/s40265‐025‐02181‐1

3. Sokolova E.V., Ladnaya N.N., Pokrovsky V.V., Kravchenko A.V., Kozyrina N.V., Yurin O.G., Chekryzhova D.G. The influence of antiretroviral therapy on the development of the HIV epidemic in the Russian Federation Epidemiology and Infectious Diseases. Current Items, 2023, vol. 13, no. 3, pp. 20–26. (In Russian) https://doi.org/10.18565/epidem.2023.13.3.20‐6

4. Rodríguez‐Galet A., Ventosa‐Cubillo J., Bendomo V., Eyene M., Mikue‐Owono T., Nzang J., Ncogo P., Gonzalez‐Alba J.M., Benito A., Holguín Á. High Drug Resistance Levels Compromise the Control of HIV Infection in Pediatric and Adult Populations in Bata, Equatorial Guinea. Viruses, 2022, vol. 15, no. 1, pp. 27. https://doi.org/10.3390/v15010027

5. World Health Organization. HIV drug resistance: brief report 2024. Geneva, 2024. Available at: https://www.who.int/publications/i/item/9789240086319 (accessed 31.07.2025)

6. Ozhmegova E.N., Bobkova M.R. HIV drug resistance: past and current trends. Problems of Virology (Voprosy Virusologii), 2022, vol. 67, no. 3, pp. 193–205. (In Russian) https://doi.org/10.36233/0507‐4088‐113

7. Bobkova M.R. Lekarstvennaya ustoichivost' VICH [HIV drug resistance]. Moscow, Chelovek Publ., 2014, 288 p. (In Russian)

8. Boffito M., Waters L., Cahn P., Paredes R., Koteff J., Van Wyk J., Vincent T., Demarest J., Adkison K., Quercia R. Perspectives on the Barrier to Resistance for Dolutegravir + Lamivudine, a Two‐Drug Antiretroviral Therapy for HIV‐1 Infection. AIDS Res Hum Retroviruses, 2020, vol. 36, no. 1, pp. 13–18. https://doi.org/10.1089/AID.2019.0171

9. Pang X., Lu H., He Q., Tang K., Ma J., Chen S., Huang J., Fang N., Xie H., Lan G., Liang S. Emergence of HIV‐1 drug resistance mutations among children and adolescents undergoing prolonged antiretroviral therapy in Guangxi. J Glob Antimicrob Resist., 2024, vol. 37, pp. 208–213. https://doi.org/10.1016/j.jgar.2024.03.013

10. Sivay M.V., Maksimenko L.V., Nalimova T.M., Nefedova A.A., Osipova I.P., Kriklivaya N.P., Gashnikova M.P., Ekushov V.E., Totmenin A.V., Kapustin D.V., Pozdnyakova L.L., Skudarnov S.E., Ostapova T.S., Yaschenko S.V., Nazarova O.I., Shevchenko V.V., Ilyina E.A., Novikova O.A., Agafonov A.P., Gashnikova N.M. HIV drug resistance among patients experiencing antiretroviral therapy failure in Russia, 2019‐ 2021. Int J AntimicrobAgents, 2024, vol. 63, no. 2, Article id: 107074. https://doi.org/10.1016/j.ijantimicag.2023.107074

11. Kirichenko A.A., Kireev D.E., Shlykova A.V. HIV‐1 drug resistance in patients with virological failure of ART in Russia (2013‐2021). Epidemiology and infectious diseases. Current issues, 2021, vol. 11, no. 3, pp. 53–62. https://doi.org/10.18565/epidem.2021.11.3.53‐62

12. Ankunda C., Emunyu J., Namasambi S., Sserunjogi C., Kyomuhangi B., Mumbere I., Nakaweesi J. Prevalence of drug resistance mutations and their association with time to virological failure in people living with HIV in Uganda. BMC Infect Dis., 2025, vol. 25, no. 1, article id: 1241. https://doi.org/10.1186/s12879‐025‐11607‐w

13. Alonso S., Salazar E., Gálvez N., Navas J., Quintana C., Orózco N., Prieto L., Navarro M.L., Guillén S., Gómez‐Alba J.M., Medina‐Sánchez C., Juarez J., Holguín A. Prevalence of acquired resistance to antiretrovirals in children and adolescents living with HIV under clinical follow‐up at the Roosevelt Hospital in Guatemala. J Infect Public Health. 2025, vol. 18, no. 9, article id: 102827. https://doi.org/10.1016/j.jiph.2025.102827

14. Kirichenko A., Kireev D., Lopatukhin A., Murzakova A., Lapovok I., Saleeva D., Ladnaya N., Gadirova A., Ibrahimova S., Safarova A. et al. Prevalence of HIV‐1 drug resistance in Eastern European and Central Asian countries. PLoS ONE, 2022, vol. 17, no. 1, article id: e0257731. https://doi.org/10.1371/journal.pone.0257731

15. Antonova A., Kazennova E., Lebedev A., Ozhmegova E., Kuznetsova A., Tumanov A., Bobkova M. Recombinant Forms of HIV‐1 in the Last Decade of the Epidemic in the Russian Federation. Viruses, 2023, vol. 15, no. 12, article id: 2312. https://doi.org/10.3390/v15122312

16. Kirichenko A.A., Kireev D.E., Lopatukhin A.E., Murzakova A.V., Lapovok I.A., Ladnaya N.N., Pokrovsky V.V. Prevalence and structure of HIV‐1 drug resistance among treatment naive patients since the introduction of antiretroviral therapy in the Russian Federation. HIV Infection and Immunosuppressive Disorders, 2019, vol. 11, no. 2, pp. 75–83. (In Russian) https://doi.org/10.22328/2077‐9828‐2019‐11‐2‐75‐83

17. Brizzi M.B., Cable T.L., Patel D.C., Williams K., Adjei Z., Fichtenbaum C.J. Heavily treatment‐experienced patients with HIV: are new mechanisms of action enough? J Int Med Res. 2024, vol. 52, no. 12, article id: 3000605241301883. https://doi.org/10.1177/03000605241301883

18. Shchemelev A.N., Semenov A.V., Ostankova Yu.V., et al. Genetic diversity and drug resistance mutations of HIV‐1 in Leningrad Region. Journal of microbiology, epidemiology and immunobiology, 2022, vol. 99, no. 1, pp. 28–37. (In Russian) https://doi.org/10.36233/0372‐9311‐216

19. Piterskiy M.V., Gusev A.G., Khodakov O.A., et al. HIV‐1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District. Journal of microbiology, epidemiology and immunobiology, 2022, vol. 99, no. 1, pp. 38–53. (In Russia) https://doi.org/10.36233/0372‐9311‐178

20. Kapustin D.V., Nalimova T.M., Ekushov V.E., Kriklivaya N.P., Halikov M.R., Krasnova E.I., Khokhlova N.I., Demchenko S.V., Pozdnaykova L.L., Sivay M.V., Totmenin A.V., Gashnikova M.P., Gotfrid L.G., Maksutov R.A., Gashnikova N.M. Patterns of HIV‐1 drug resistance among HIV‐infected patients receiving first‐line antiretroviral therapy in Novosibirsk Region, Russia. J Glob Antimicrob Resist., 2023, vol. 35, pp. 1–5. https://doi.org/10.1016/j.jgar.2023.07.013

21. Specialized Research Department for AIDS Prevention and Control, Federal Budgetary Institution of Science, Central Research Institute of Epidemiology, Rospotrebnadzor. HIV infection in the Russian Federation as of June 30, 2023. (in Russian) Available at: chrome‐ extension://efaidnbmnnnibpcajpcglclefindmkaj/https://hivhub.ru/wp‐content/uploads/2024/04/vich2023.pdf (accessed on 20.12.2024).

22. Pokrovsky V.V., Ladnaya N.N., Sokolova E.V. Federal Scientific and Methodological Center for the Prevention and Control of AIDS. HIV INFECTION Information Bulletin no. 48 (In Russian) Available at: chrome‐extension://efaidnbmnnnibpcajpcglclefindmkaj/http://www.hivrussia.info/wp‐content/uploads/2024/11/hiv‐infection‐info‐bulletin‐48.pdf (accessed 20.05.2024)

23. Shchevchenko V.V. Statistics of HIV infection in the Altai Territory. (In Russian) Available at: https://altaids22.ru/spetsialistam/statistika/ (accessed 15.02.2025)

24. Polyakov A.N., Polyakova A.V., Saf'yanova T.V. Assessment of the epidemiological situation on the incidence of HIV infection in the Altai Territory in 2006–2014. Byulleten' meditsinskoi nauki [Medical Review. Science and Practice]. 2016, vol. 1, no. 5. pp. 12–15. (In Russian) Available at: https://cyberleninka.ru/article/n/zabolevaemost‐vich‐infektsiey‐na‐territorii‐altayskogo‐kraya‐v‐2006‐2014‐gg (accessed: 15.10.2025).

25. Lukyanenko N.V. et al. Analysis of HIV infection incidence in the Altai Territory in 2022. Yakut Medical Journal. 2025, no. 4, pp. 80–84. (In Russian)

26. Kazennova E.V., Antonova A.A., Ozhmegova E.N., Demyanenko E.R., Minakova M.V., Belousova O.V., Gromov K.B., Bobkova M.R. Genetic analysis of HIV‐1 in the Altai kray: the further spread of the CRF63_02A1 variant in Western Siberia. HIV Infection and Immunosuppressive Disorders, 2020, vol. 12, no. 1, pp. 47–57. (In Russian) https://doi.org/10.22328/2077‐9828‐2020‐12‐1‐47‐57

27. Reshetnikov A.V., Pavlov S.V. Modern social portrait of HIV‐infected Russia. Immunology, 2018, vol. 39, no. 2–3, pp. 100–107. (In Russian) https://doi.org/10.18821/0206‐4952‐2018‐39‐2‐3‐100‐107

28. Zagdyn Z.M., Kobesov N.V., Denyushenkov V.L., Sterlikov S.A. A public health perspective on global burden of HIV/AIDS in Russia: DALY due to HIV infection. Part 2. HIV Infection and Immunosuppressive Disorders, 2025, vol. 17, no. 2, pp. 32–43. (In Russian) https://doi.org/10.22328/2077‐9828‐2025‐17‐2‐32‐43

29. Yamaguchi J. et al. Brief report: complete genome sequence of CG‐0018a‐01 establishes HIV‐1 subtype L. JAIDS Journal of Acquired Immune Deficiency Syndromes, 2020, vol. 83, no. 3, pp. 319–322. https://doi.org/10.1097/QAI.0000000000002246

30. Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide. Current Opinion in HIV and AIDS, 2019, vol. 14, no. 3, pp. 153–160. https://doi.org/10.1097/COH.0000000000000534

31. Ekushov V.E., Halikov M.R., Totmenin A.V., Antonets M.E., Tregubchak T.V., Murzin A.I., Pavlova M.N., Troianova A.M., Adusheva T.P., Beniova S.N. et al. Characterization of a New HIV‐1 Second‐Generation Circulating Recombinant Form CRF173_63A6 in the Jewish Autonomous Region of Russia. Pathogens, 2025, vol. 14, no. 9, article id: 836. https://doi.org/10.3390/pathogens14090836

32. Sivay M.V., Maksimenko L.V., Osipova I.P., Nefedova A.A., Gashnikova M.P., Zyryanova D.P., Ekushov V.E., Totmenin A.V., Nalimova T.M., Ivlev V.V., Kapustin D.V., Pozdnyakova L.L., Skudarnov S.E., Ostapova T.S., Yaschenko S.V., Nazarova O.I., Chernov A.S., Ismailova T.N., Maksutov R.A., Gashnikova N.M. Spatiotemporal dynamics of HIV‐1 CRF63_02A6 sub‐epidemic. Front Microbiol., 2022, vol. 31, no. 13, article id: 946787. https://doi.org/10.3389/fmicb.2022.946787

33. Halikov M.R., Ekushov V.E., Totmenin A.V., Gashnikova N.M., Antonets M.E., Tregubchak T.V., Beniova S.N. Identification of a novel HIV‐1 circulating recombinant form CRF157_A6C in Primorsky Territory, Russia. Journal of Infection. 2024, vol. 88, no. 2, pp. 180–182.

34. Maksimenko L.V., Sivay M.V., Antonets M.E., Tregubchak T.V., Totmenin A.V., Skudarnov S.E., Ostapova T.S., Yashenko S.V., Agafonov A.P., Gashnikova N.M. Expanding HIV‐1 diversity in Russia: Novel circulating recombinant form between subtypes A6 and B (CRF147_A6B). J Infect., 2024, vol. 89, no. 5, article id: 106308. https://doi.org/10.1016/j.jinf.2024.106308

35. Halikov M.R., Ekushov V.E., Totmenin A.V., Gotfrid L.G., Sklyar L.F., Soloveva N.P., Serdtseva E.N., Shportova M.I., MartynchenkoZh.A., Beniova S.N., Ermolickaja S.A., Gorelova I.S., Gashnikova N.M. The role of recombination variability to the formation of the population the HIV‐1 population circulating in the Primorsky Krai, Russia. South of Russia: ecology, development, 2023, vol. 18, no. 4, pp. 125–133. (In Russian) https://doi.org/10.18470/1992‐1098‐2023‐4‐125‐133

36. Lebedev A. et al. The Molecular Epidemiology of HIV‐1 in Russia, 1987–2023: Subtypes, Transmission Networks and Phylogenetic Story. Pathogens. 2025, vol. 14. no. 8, article id: 738.

37. Usach I., Melis V., Peris J.E. Non‐nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. Journal of the International AIDS Society, 2013, vol. 16, no. 1, article id: 18567. https://doi.org/10.7448/IAS.16.1.18567