#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Distribúcia HIV-1 subtypov a rezistencie na ART u HIV-infikovaných osôb na Slovensku (2019–2021)


Autoři: A. Kovářová 1,2;  D. Valkovičová Staneková 2;  M. Hábeková 2;  M. Takáčová 2
Působiště autorů: Department of Laboratory Investigation Methods in Healthcare, Faculty of Health Sciences and Social Work, The University of Trnava, Trnava, Slovak Republica 1;  National Reference Centre for HIV/AIDS Prevention, Slovak Medical University, Bratislava, Slovak Republic 2
Vyšlo v časopise: Epidemiol. Mikrobiol. Imunol. 72, 2023, č. 4, s. 203-212
Kategorie: Původní práce

Souhrn

Cieľ: Cieľom štúdie bolo popísať výskyt HIV-1 subtypov a HIV-1 kmeňov rezistentných na antiretrovírusovú liečbu (ART) u HIV pozitívnych osôb novo diagnostikovaných na Slovensku v rokoch 2019–2021.

Materiál a metódy: Študijnú skupinu tvorilo 184 HIV pozitívnych naivných pacientov novo diagnostikovaných na Slovensku v rokoch 2019–2021. Vírusová HIV-1 RNA bola izolovaná z plazmy pomocou QIAamp Viral RNA Mini Kit (QIAGEN, Nemecko). Pre RT-PCR a sekvenovanie oblasti HIV pol sme použili interné postupy podľa protokolu ANRS AC11 pre RT (reverzná transkriptáza), PRO (proteáza) a IN (integráza) (ANRS AC11 Resistance Study Group, 2015). Analýzu sekvencií sme uskutočnili pomocou softvéru Sequencing Analysis Software v5.3 (Applied Biosystems®). HIV sekvencie boli manuálne upravené pomocou BioEdit (verzia 7.2.5), porovnané s konsenzuálnymi HIV-1 sekvenciami v Los Alamos Sequence Database (URL 2), zarovnané pomocou CLUSTAL W (Labarga et al., 2007) a softvérových balíkov BioEdit (verzia 7.2 .5) (Hall, 1999). Na vyhodnotenie sekvencie sme použili algoritmus HIVDB (verzia 9.0) Stanfordskej databázy HIV liekovej rezistencie (URL 1.). Na analýzu HIV-1 subtypov sme použili nástroj REGA HIV-1 Subtyping Tool (De Oliviera et al., 2005) a fylogenetickú analýzu sme vypracovali pomocou programu MEGA X (Kumar et al., 2018).

Výsledky: Fylogenetickú analýzu sme vykonali zo vzoriek 184 osôb, kde sme odhalili najrozšírenejší subtyp B (129/184, 70,11 %) prevládajúci v populácii u mužov, ktorí majú sex s mužmi (MSM) (96/129 74,42 %). Čo sa týka non-B subtypov (55/184, 29,89 %), najrozšírenejší bol subtyp A (48/184, 26,09 %) v porovnaní so subtypom F (F1) (3; 1,63 %), C (1; 0,54 %) a cirkulujúcimi rekombinantnými formami CRF02_AG (2; 1,09 %), CRF01_AE (1; 0,54 %). U 9,24 % (17/184) vzoriek sme zistili prítomnosť 25 mutácií asociovaných s HIV rezistenciou na ART, z toho 7,07 % (13/184) na inhibítory reverznej transkriptázy, 1,66 % (3/181) na inhibítory proteázy a 1,32 % (2/151) na inhibítory integrázy. Okrem toho u 1,63 % (3/184) pacientov bola prítomná viactriedna rezistencia. Mutácie asociované s rezistenciou HIV na ART sa našli u 9,30 % osôb infikovaných podtypom B.

Záver: Naša štúdia potvrdila pretrvávajúci najvyšší výskyt subtypu B s mierne klesajúcou tendenciou v porovnaní s minulými rokmi. Detekcia mutácií vytvárajúcich rezistenciu HIV na ART podčiarkuje potrebu testovania rezistencie u naivných pacientov ešte pred začatím ART na Slovensku.


Zdroje
  1. Abram ME, Ferris AL, Shao W, et al. Nature, position, and frequency of mutations made in a single cycle of HIV-1 replication. J Virol, 2010;84(19):9864–9878.
  2. Alaeus A. Significance of HIV-1 genetic subtypes. Scand J Infect Dis, 2000;32(5):455–463.
  3. Alexiev I, Campbell EM, Knyazev S, et al. Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria. Viruses, 2020;12(4):441.
  4. ANRS AC11 Resistance Study Group (2015): PCR and sequencing procedures: HIV-1 [online]. Version January 2015 [cit. 2023-0206]. Available at www: https://hivfrenchresistance.org/wp-content/uploads/2021/10/ANRS-procedures.pdf
  5. Asante-Appiah E, Lai J, Wan H, et al. Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates. Antimicrob Agents Chemother, 2021; 65(12):e01216–1221.
  6. Azijn H, Tirry I, Vingerhoets J, et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother, 2010;54(2):718–727.
  7. Beloukas A, Psarris A, Giannelou P, et al. Molecular epidemiology of HIV-1 infection in Europe: An overview. Inf Gen Evol, 2016;46:180–189.
  8. Cuevas JM, Geller R, Garijo R, et al. Extremely High Mutation Rate of HIV-1 In Vivo. PLoS Biol, 2015;13(9):1002251.
  9. Čereš A, Staneková D, Hábeková M, et al. 2018. HIV genetic diversity and occurrence of the HLA-B*57:01 allele in newly diagnosed HIV-positive patients in Slovakia in 2015–2016. Clinical Microbiology Reports. pp. 39, EV 2992/09, Year XVIII., Number SA/2018. ISSN 1338–645X.
  10. Davanos N, Panos G, Gogos Ch, Mouzaki A. HIV-1 subtype characteristics of infected persons living in southwestern Greece. HIV AIDS (Auckl), 2015;7:277–283.
  11. Delgado E, Benito S, Montero V, et al. Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain. Front Microbiol, 2019;10.
  12. De Oliveira T, Deforche K, Cassol S, et al. An automated genotyping system for analysis of HIV-1 and other microbial sequences. Bioinformatics, 2005;21(19):3797–3800.
  13. Felsenstein J. Confidence limits on phylogenies: An approach using the bootstrap. Evolution, 1985;39(4):783–791.
  14. Feng M, Wang D, Grobler JA, et al. In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. Antimicrob Agents Chemother, 2015;59(1):590–598.
  15. Hall T. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser, 1999;41:95–98.
  16. Hauser A, Hofmann A, Meixenberger K, et al. Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses. PLoS ONE, 2018;13(11):e0206234.
  17. Hábeková M, Kovářová A, Takáčová M, Valkovičová Staneková D. Distribution of subtypes HIV1 in Slovakia: update 2017 – 2018. Acta Virol, 2023. ISSN 0001–723X.
  18. Hábeková M, Takáčová M, Lysy J, et al. Genetic Subtypes of HIV Type 1 Circulating in Slovakia. AIDS Research and Human Retroviruses, 2010;26(10):1103–1107.
  19. Hemelaar J, Elangovan R, Yun J, et al. Global and regional molecular epidemiology of HIV-1, 1990–2015: A systematic review, global survey, and trend analysis. Lancet Infect Dis, 2019;19:143– 155.
  20. Hemelaar J. The origin and diversity of the HIV-1 pandemic. Trends Mol Med, 2012;18(3):182–192.
  21. Hofstra LM, Sauvageot N, Albert J, et al. Ryding, for the SPREAD Program, Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe. Clin Infect Dis, 2016;62(5):655–663.
  22. Hofstra LM, Seguin-Devaux C, Struck D, et al. The prevalence of drug resistance mutations in newly-diagnosed HIV-patients in Europe: interactive monitoring. In: Hofstra M. HIV Drug Resistance. Utrecht: University of Utrecht; 2019. pp. 63–77. ISBN: 978-94-6361-225-8
  23. Chabadová Z, Habeková M, Truska P, et al. Distribution of HIV-1 subtypes circulating in Slovakia (2009–2012). Acta Virol, 2014;58(4):317–324.
  24. Junqueira DM, de Matos Almeida SE. HIV-1 subtype B: Traces of a pandemic. Virology, 2016;495:173–184.
  25. Kimura M. A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences. J Mol Evol, 1980;16(2):111–120.
  26. Klundert MAA, Antonova A, Di Teodoro G et al. Molecular Epidemiology of HIV-1 in Eastern Europe and Russia. Viruses, 2022;14(10):2099.
  27. Konstantinos A, Albert J, Mamais I, et al. Global dispersal pattern of HIV-1 CRF01_AE: A genetic trace of human mobility related to heterosexual activities centralized in South-East Asia J Infect Dis, 2015;211:1735–1744.
  28. Kostaki EG, Limnaios S, Adamis G, et al. Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors. HIV Medicine, 2022;23(11):1143–1152.
  29. Kumar S, Stecher G, Li M, et al. MEGA X: Molecular Evolutionary Genetics Analysis across computing platforms. Mol Biol Evol, 2018;35(6):1547–1549.
  30. Labarga A, Valentin F, Anderson M, Lopez R. Web services at the European bioinformatics institute. Nucleic Acids Res, 2007; 35(Web Server issue): W6–W11.
  31. Lai MT, Feng M, Falgueyret JP, et al. In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother, 2014;58(3):1652–1663.
  32. Lee HY, Perelson AS, Park SC, Leitner T. Dynamic correlation between intrahost HIV-1 quasispecies evolution and disease progression. PLoS Comput Biol, 2008;4(12):e1000240.
  33. Lorenzin G, Gargiulo F, Caruso A, et al. Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis. Microorganisms, 2020;8(1):36.
  34. Lunar MM, Vandamme AM, Tomažič J, et al. Bridging epidemiology with population genetics in a low incidence MSM-driven HIV-1 subtype B epidemic in Central Europe. BMC Infect Dis, 2015;15:65.
  35. Magiorkinis G, Angelis K, Mamais I, et al. The global spread of HIV-1 subtype B epidemic. Infect Genet Evol, 2016;46:169–179.
  36. Matuzzi L, Melengu T, Falasca F, et al. Transmitted drug resistance mutations and trends of HIV-1 subtypes in treatment-naïve patients: A single-centre experience. J Glob Antimicrob Resist, 2020;20:298–303.
  37. Melikian GL, Rhee SY, Varghese V, et al. Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother, 2014;69(1):12–20.
  38. Mravčík V, Pitoňák M, Hejzák R, et al. HIV epidemic among men who have sex with men in the Czech Republic, 2016: high time for targeted action. Euro Surveill. 2017;22(48):17–00079.
  39. Murillo W, Veras NMC, Prosperi MCF, et al. A single early introduction of HIV-1 subtype B into Central America accounts for most current cases. J Virol, 2013;87:7463–7470.
  40. Mustafa A, Akbay B, Davlidova S, et al. Origin and evolution of subtype B variants in the former Soviet Union countries. Infect Genet Evol, 2023;108:105402.
  41. Neogi U, Häggblom A, Santacatterina M, et al. Temporal Trends in the Swedish HIV-1 Epidemic: Increase in Non-B Subtypes and Recombinant Forms over Three Decades. PLoS ONE, 2014;9(6):e99390.
  42. Oroz M, Begovac J, Planinić A, et al. Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia. Sci Rep, 2019;9(1):17307.
  43. Paraskevis D, Nikolopoulos GK, Magiorkinis G, et al. The application of HIV molecular epidemiology to public health. Infect Genet Evol, 2016;46:159–168.
  44. Parczewski M, Leszczyszyn-Pynka M, Witak-Jedra M, et al. Distribution and time trends of HIV-1 variants in Poland: Characteristics of non-B clades and recombinant viruses. Infect Genet Evol, 2016;39:232–240.
  45. Pingarilho M, Pimentel V, Miranda MNS, et al. HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019. Front Microbiol, 2022;13:823208.
  46. Public Health Authority of the Slovak Republic. Incidence of infection in the Slovak Republic until June 30, 2022 [online]. 2022 [cit. 2023-02-01]. Available at www: <https:// www.uvzsr.sk/index.php?option=com_content&view=ar- ticle&id=5463%3Avyskyt-hiv-infekcie-v-slovenskej-repub like-k-306-2022&catid=283%3Ahivaids&Itemid=112>.
  47. Rhee SY, Grant PM, Tzou PL, et al. A systematic review of the genetic mechanisms of dolutegravir resistance. J Antimicrob Chemother, 2019;74(11):3135–3149.
  48. Rhee SY, Parkin N, Harrigan PR, et al. Genotypic Correlates of Resistance to the HIV-1 Strand Transfer Integrase Inhibitor Cabotegravir. Review 2022 Sept. 01, PREPRINT (Version 1). Available at www: https://doi.org/10.21203/rs.3.rs-2012078/v1.
  49. Rhee SY, Schapiro JM, Saladini F, et al. Potential Role of Doravirine for the Treatment of Patients with Transmitted Drug Resistance. AIDS Res Ther, 2023;20:8.
  50. Rimsky L, Vingerhoets J, Van Eygen V, et al. Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. J Acquir Immune Defic Syndr, 2012 Jan 1;59(1):39–46.
  51. Rizzardini G, Overton ET, Orkin C, et al. Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials. J Acquir Immune Defic Syndr, 2020;85(4):498–506.
  52. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol, 1987;4(4):406– 425.
  53. Serwin K, Scheibe K, Horecki M, et al. Detection of Polish cases of highly virulent subtype B of HIV-1 originating in the Netherlands. Journal of Medical Virology, 2022;95(1):28154.
  54. Serwin K, Urbańska A, Scheibe K, et al. Molecular epidemiology and HIV-1 variant evolution in Poland between 2015 and 2019. Sci Rep, 2021;11:16609.
  55. Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med, 2011;1(1):a006841.
  56. Tambuyzer L, Nijs S, Daems B, et al. Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptbility and virologic response to etravirine. J Acquir Immune Defic Syndr, 2011;58(1):18–22.
  57. Tsiang M, Jones GS, Goldsmith J, et al. Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Antimicrob Agents Chemother, 2016;60(12):7086–7097.
  58. UNAIDS. Global HIV & AIDS statistics – Fact sheet [online]. 2023 [cit. 2023-02-03]. Available at www: <https://www.unaids.org/ en/resources/fact-sheet>.
  59. URL 1. STANFORD HIVDB PROGRAM. Release notes [online]. 2021 [cit. 2023-02-04]. Available at www: <https://hivdb.stanford.edu/page/release-notes/>.
  60. URL 2. NRTI Resistance Notes [online]. 2022 [cit. 2023-02-04]. Available at www: <https://hivdb.stanford.edu/dr-summary/ resistance-notes/NRTI/>.
  61. URL 3. PI Resistance Notes [online]. 2022 [cit. 2023-02-04]. Available at www: <https://hivdb.stanford.edu/dr-summary/resistance-notes/PI/>.
  62. URL. 4. HIV sequence database [online]. 2019 [cit. 2023-0119]. Available at www: <https://www.hiv.lanl.gov/content/se- quence/LOCATE/locate.html>.
  63. Vingerhoets J, Tambuyzer L, Azijn H, et al. Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies. AIDS, 2010;24(4):503–514.
  64. Mortier V, Debaisieux L, Dessilly G, et al. Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019. Open Forum Infect Dis, 2022;9(7):195.
  65. Westen GJP, Hendriks A, Wegner JK, et al. Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol, 2013. Available at www: https://doi.org/10.1371/journal. pcbi.1002899.
  66. WHO. HIV [online]. 2022 [cit. 2023-02-04]. Available at www:<https://www.who.int/news-room/fact-sheets/detail/hiv-  aids>.
  67. Wymant CH, Bezemer D, Blanquart F, et al. A highly virulent variant of HIV-1 circulating in the Netherlands. Science, 2022;375(6580):540–545.
  68. Yamaguchi J, McArthur C, Sthreshley L, et al. Brief Report: Complete genome sequence of CG-0018a-01 establishes HIV-1 subtype L. J Acquir Immune Defic Syndr, 2020;83(3):319–322.
Štítky
Hygiena a epidemiologie Infekční lékařství Mikrobiologie

Článek vyšel v časopise

Epidemiologie, mikrobiologie, imunologie

Číslo 4

2023 Číslo 4
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Svět praktické medicíny 1/2024 (znalostní test z časopisu)
nový kurz

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Význam metforminu pro „udržitelnou“ terapii diabetu
Autoři: prof. MUDr. Milan Kvapil, CSc., MBA

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#