Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

There is concern that the widespread use of antiretroviral drugs (ARV) to treat human immunodeficiency virus 1 (HIV-1) infection may result in the emergence of transmission of drug-resistant virus among persons newly infected with HIV-1. Russia is one of a growing number of countries in the world where drug-resistant HIV is becoming a serious health problem because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.

Materials and methods. We performed a genetic analysis of the HIV-1 plasma derived pol gene among the newly diagnosed ART-naïve HIV-1 infected patients during the period from November 2018 to October 2019 in the St. Petersburg Clinical Infectious Diseases Hospital named after S.P. Botkin. We used reverse transcriptase polymerase chain reaction (RT-PCR) followed by direct sequencing of PCR products to determine the prevalence of primary drug resistance (PDR) conferring mutations. HIV-1 genotypes were determined by phylogenetic analysis.

Results. The predominant HIV-1 subtype was A1 (87.2%), followed by B (11.8%) and CRF06_cpx (1%). The overall prevalence of PDR was 11%. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors (NRTIs) was found in 8 individuals, to any non NRTIs in 5 subjects, and to any protease inhibitors in 1 case. Multidrug-resistant virus was identified in 2 individuals (2%).

Conclusion. The distribution of HIV-1 genotypes in St. Petersburg, Russia is diverse. The emerging prevalence of PDR in ART-naïve patients demonstrates the significance of constant monitoring due to the challenges it presents towards treatment.

1. UNAIDS (2018). UNAIDS data 2018. State of the epidemic in Eastern Europe and Central Asia. Р. 273–278.

2. Beyrer C., Wirtz A.L., O’Hara G., Léon N., Kazatchkine M. The expanding epidemic of HIV-1 in the Russian Federation // PLOS Medicine. 2017. Vol. 14 (11). e1002462. https://doi.org/10.1371/journal.pmed.1002462.

3. Clark F. World Report: Gaps remain in Russia’s response to HIV/AIDS // The Lancet. 2016. Vol. 388 (10047). Р. 857–858. https://doi.org/10.1016/S0140-6736(16)31480-5.

4. Belyakov N.A., Rassokhin V.V., Semenov A.V., Konovalova N.V., Ogurtsova S.V., Svetlichnaya Yu.S., Boeva E.V., Bobreshova A.S., Esaulenko E.V., Sukhoruk A.A. HIV infection and comorbidal conditions in the northwestern federal district of the Russian Federation in 2016 // Аnalytical review. St. Petersburg, 2017.

5. UNAIDS. Global HIV & AIDS statistics 2020. Р. 1–7.

6. UNAIDS 90–90–90, an ambitious treatment target to help end the AIDS epidemic. 2017. Р. 1–40.

7. Phillips A.N., Stover J., Cambiano V., Nakagawa F., Jordan M.R., Pillay D. et al. Impact of HIV drug resistance on HIV/AIDS associated mortality, new infections and antiretroviral therapy program costs in sub-Saharan Africa // Journal of Infectious Diseases. 2017. Vol. 215 (9). Р. 1362–1365.

8. WHO (2017). Guidelines on the public health response to pretreatment HIV drug resistance. Р. 1–84.

9. Hofstra L.M. High rates of transmission of drug-resistant HIV in Aruba resulting in reduced susceptibility to the WHO recommended first-line regimen in nearly half of newly diagnosed HIV-infected patients // Clinical Infectious Diseases. 2017. Vol. 64. Р. 1092–1097.

10. Sanchez Rivas E., Nijhuis M., Bank L.E.A., Wilkinson E, Kelly K., Boden D., Hurley A., Zhang L. et al. HIV-1 drug resistance in newly infected individuals // The Journal of the American Medical Association. 1999. Vol. 282 (12). Р. 1135–1141.

11. Chauhan C.K., Lakshmi P.V.M., Sagar V., Sharma A., Arora S.K., Kumar R. Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India // AIDS Research and Treatment. 2019. 8 p.

12. Lebedeva N.N., Zverev S.Y., Kulagin V.V., Kurina N.V., Pronin A.Yu., Mikova O.E., Milovanova I.I., Polovitsa N.V., Sandyreva T.P., Sizova N.V., Sklyar L.F., Tertyshnaya Yu. N., Belkina N.S., Shemshura A.B., Bobkova M.R. HIV drug resistance early warning indicators and their assessment in some regions of Russia // HIV Infection and Immunosuppressive Disorders. 2018. Vol. 10 (4). Р. 67–75.

13. Struck D., Lawyer G., Ternes A.M., Schmit J.C., Bercoff D.P. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification // Nucleic Acids Research. 2014. Vol. 42. Р. 144.

14. Pineda-Pena A.C., Faria N.R., Imbrechts S., Libin P., Abecasis A.B., Deforche K. et al. Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools // Infection, Genetics and Evolution. 2013. Vol. 19. Р. 337–348.

15. WHO (2016). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. 2nd ed. Clinical guidelines HIV diagnosis, 2016. Р. 1–34.

16. Maldonado J. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug- Resistant Mutations // Viruses. 2018. Vol. 10 (7). Р. 376.

17. Hylton E., Wirtz A.L., Zelaya C.E, Latkin C., Peryshkina A., Mogilnyi V. et al. Sexual Identity, Stigma, and Depression: the Role of the «Antigay Propaganda Law» in Mental Health among Men Who Have Sex with Men in Moscow, Russia // Journal of Urban Health. 2017. Vol. 94 (3). Р. 319–329.

18. Wirtz A.L., Zelaya C.E., Peryshkina A., Latkin C., Mogilnyi V., Galai N. et al. Social and structural risks for HIV among migrant and immigrant men who have sex with men in Moscow, Russia: Implications for prevention // AIDS Care. 2014. Vol. 26 (3). Р. 387–395.

19. Deniz G., Cristiana O., Serhat U., Josip B The growing HIV epidemic in Central Europe: a neglected issue? // Journal of Virus Eradication. 2016. Vol. 2 (3). Р. 156–161.

20. Peltzer K. Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, South Africa // African Health Sciences. 2012. Vol. 12. Р. 8–16.

21. Zenin P.V., Pronin A., Serkov I.L., Khametova K.M., Orlova-Morozova E.A., Giliazova A.V. et al. Molecular epidemiology of HIV-1 strains in the Moscow Region // Problems of Virology. 2010. Vol. 55. Р. 25–29.

22. Vinogradova A., Delgado E., Rakhmanova A., Yakovlev A., Cuevas M. T., Nájera R Thomson M. M. Molecular Epidemiology of HIV-1 in St. Petersburg, Russia: Predominance of Subtype A, Former Soviet Union Variant, and Identification of Intrasubtype Subclusters // Journal of Acquired Immune Deficiency Syndromes. 2009. Vol. 51 (3). Р. 332–339.

23. Lebedev A., Мoskaleychik F., Pronin A., Kazennova E., Bobkova M. Human Immunodeficiency Virus-1 Diversity in the Moscow Region, Russia: Phylodynamics of the Most Common Subtypes // Frontiers in Microbiology. 2019. Vol. 10. doi: 10.3389/fmicb.2019.00320.

24. Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide // Current Opinion in HIV and AIDS. 2019. Vol. 14 (3). Р. 153–160.

25. Buchacz K., Young B., Palella F. J., Armon C., Brooks J. T… Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999–2011 // Journal of Antimicrobial Chemotherapy. 2015. Vol. 70 (8). Р. 2337–2346.

26. Hofstra L.M. et al. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe // Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2016. Vol. 62. Р. 655–663.

27. Zhao S., Feng Y., Hu J. et al. Prevalence of Transmitted HIV drug resistance in antiretroviral treatment naïve newly diagnosed individuals in China // Scientific Reports. 2018. Vol. 8. Р. 12273.

28. Pace C.A., Lioznov D., Cheng D.M., Wakeman S.E., Raj A., Walley A.Y., Samet J.H. Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia. International // Journal of STD & AIDS. 2012. Vol. 23 (12). Р. 853–858.

29. Bennett D.E., Myatt M., Bertagnolio S., Sutherland D., Gilks C.F. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment // Antiviral Therapy. 2008. Vol. 13 (2). p. 25–36.

30. 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 naïve patients since the introduction of antiretroviral therapy in the Russian Federation // HIV Infection and Immunosuppressive Disorders. 2019. Vоl. 11 (2). Р. 75–83.

31. Oroz M., Begovac J., Planinić A. et al. Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia // Scientific Reports. 2019. Vоl. 9. Р. 17307.

32. Zaitseva N.N., Parfenova O.Yu. Analysis of spread of initial resistance of HIV to antiretroviral medicines in Privolzhsky Federal District // World of Transport and Transportation. 2016. Vоl. 14 (3). Р. 93–35.