Method for measurement of the size of the HIV cell reservoir and for its determination in patients who are not experienced with ART


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To develop a method for measurement of the size of the reservoir for its determination in HIV-infected individuals who are not experienced with ART and to analyze its relationship to viral load (VL), duration of infection, and immune status. Materials and methods. Examinations were made in 268HIV-infected patients with no ART experience with known dates of infection At the time of blood sampling, VL and the immune status index were determined in patients. DNA was isolated from peripheral blood mononuclear cells (PBMC) and quantified by real-time PCR. The size of the reservoir was calculated as the number of copies of the proviral DNA to the total number of cells. Results are expressed as log10 copies/106 PBMC. Results. HIV DNA concentration ranged from 0.04 to 3.84 log-0, HIV DNA copies/106 PBMC (median 2.22, interquartile range 1.74-2.72 log10 HIV DNA copies/106 PBMC). The teservoir size correlated with VL (r = 0.526; p < 0.01), immune status (r = -0.189; p < 0.05) and duration of infection (r = -0.282; p < 0.01). Conclusion. The concentration of HIV DNA as a marker of the size of the viral reservoir provides additional information about the course of the disease. It can be recommended to use this indicator in conjunction with VL and immune status for early infections.

Full Text

Restricted Access

About the authors

Nikita A. Kvasov

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: kvasov.bio@gmail.com
Junior Researcher

Angelina K. Polyakova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: angelina.polya@gmail.com
Junior Researcher

Alexey E. Lopatukhin

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: a.lopatukhin@gmail.com
Researcher

Anastasia V. Murzakova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: murzakova_a.v@mail.ru
Researcher

Andrey B. Shemshura

Cinical Center for AIDS Prevention and Control, Ministry of Health of the Krasnodar Territory

Email: shemsh@mail.ru
Cand. Med. Sci., Clinical Laboratory Diagnostician

Dmitry E. Kireev

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Cand. Biol. Sci., Head, Laboratory of Diagnostics and Molecular Epidemiology of HIV Infection

References

  1. Deeks S.G., Lewin S.R., Havlir D.V. The end ofAIDS: HIV infection as a chronic disease. The Lancet 2013; 382(9903), 1525-33. https://doi.org/10.1016/S0140-6736(13)61809-7
  2. Турсунов Р.А., Канесдри В.Г., Симонова Е.Г., Раичич Р.7. Антиретровирусная терапия-новая эпоха профилактики ВИЧ-инфекции. ВИЧ-инфекция и иммуносупрессии 2018; 10(1): 37-46. https://doi.org/10.22328/2077-9828-2018-10-1-37-46
  3. Barton K., Winckelmann A., Palmer S. HIV-1 reservoirs during suppressive therapy. Trends in Microbiology 2016; 24(5), 345-15. https://doi.org010.W16rj.tim.2016.01.006
  4. Abdel-Mohsen M., Richman D., riliciano R.F., Nusse/zweig M.C., Howell B.J., Martinez-Picado J., Montaner L.J. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nature Medicine 2020; 26(9): 1339-50. https://doi.org/10.1038/s41V91-020-1022-1
  5. Kiselinova M., De Spiegelaerr Wr Buzon M.J., Malatinkova E.d LichterVeld I'M., Vandekerckhove L. Integrated and total HIV-1 DNA predict ex vivo viral outgrowth. PLoS Pathogens 2016; 12(3); е1005472. https://doi.org/10.1371/journal.ppat.1005472
  6. Tsiara C.G., Nikolopoulos G.K., Bagos P. G., Goujard C., Katzenstein T.L., Minga A.K. , Hatzakis A. Impact of HIV type l DNA levels on spontaneoos diaease progression: a meta-analysis. AIDS Research and Human Retroviruses 2012; 28(4): 366-73. httpsTdoi.org/10.1089/aid. 2011.0032
  7. Shiramizu 13., Paul IP., Williams A., Shikuma C., Watters М., Grove J., Valcour V. HIV proviral DNA associated with decreased neuropsychological function. J. Neuropsychiatry Clin. Neurosci. 2007; 1-9(2): 157-63. https://doi.org/10.1176/jnp.2007.19.2.157
  8. Parisi S.G., Andreis S., Mengoli C., Scaggiante R., Ferretto R., Manfrin V., Sarmati L. Baseline cellular HIV DNA lo ad predicts HIV DNA decline and residual HIVplasma levels during effective antiretroviral therapy. J. Clin. Microbiol. 2012; 50(2): 258-63. https://doi.org/10.1128/JCM.06022-11
  9. Rouzioux C., Hubert J.B., Burgard М., Deveau C., Goujard С., Вагу М., Meyer L. Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T cell counts. J. Infectious Diseases 2005; 192(1), 46-55. https://doi.org/10.1086/430610
  10. Бобкова M.R Стратегии излечения ВИЧ-инфекции: основные методологические подходы и проблемы их реализации. ВИЧ-инфекция и иммуносупрессии 2020; 12(1): 22-31. https://doi.org/10.22328/2077-9828-2020-12-l-22-31
  11. Wong J. K., Hezareh М., Gunthard H. F., Havlir D.V., Ignacio C.C., Spina C.A., Richman D.D. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 1997; 278(5341): 1291-5. https://doi.org/10.1126/science.278.5341.1291
  12. Butler S.L., Hansen M.S., Bushman F.D. A quantitative assay for HIV DNA integration in vivo. Nature Medicine 2001; 7(5): 631-4. https://doi.org/10.1038/87979
  13. Bruner K. M., "Wang Z., Simonetti F.R., BenderA.M. , Kwon K.J., Sengupta S., Siliciano R.F.A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 2019: 566(7742): 120-5. https://doi.org/10.1038/s41586-019-0898-8
  14. Gaebler C., Lorenzi J.C., Oliveira T.Y., Nogueira L., Ramos V., Lu C. L., Nussenzweig M.C. Quadruplex qPCR for qualitative and quantitative analysis of the HIV-1 latent reservoir. bioRxiv 2019; 641951. https://doi.org/10.1101/641951
  15. Веселова Е.И., Каминский Г.Д., Самойлова А.Г., Васильева И.А. (2019). Резервуар ВИЧ у больных ВИЧ-инфекцией. Туберкулез и болезни легких 2019; 97(5): 50-7. https://doi.org/10.21292/2075-1230-2019-97-5-50-57
  16. Rouzioux C., Avettand-Fenoel V. Total HIV DNA: a global marker of HIV persistence. Retrovirology 2018; 15(1): 1-7. https://doi.org/10.1186/sl2977-018-0412-7
  17. Wang Z., Simonetti F.R., Siliciano R.F., Laird G.M. Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir. Retrovirology 2018; 15(1): 1-9. https://doi.org/10.1186/s12977-018-0404-7
  18. Imamichi H., Dewar R.L., Adelsberger J.W., Rehm C.A., O’Doherty U., Paxinos E., Lane H.C. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proceedings of the National Academy of Sciences 2016; 113(31): 8783-8. https://doi.org/10.1073/pnas.1609057113
  19. Pham H.T., Mespl Me T. The latest evidence for possible HIV-1 curative strategies. Drugs in Context 2018; (7). doi: 10.7573/dic.212522
  20. Sengupta S., Siliciano R.F. Targeting the latent reservoir for HIV-1. Immunity 2018; 48(5): 872-95. https://doi.org/10.1016/j.immuni.2018.04.030
  21. Saitoh A., Hsia K., Fenton T., Powell C.A., Christopherson C., Fletcher C.V., Spector S.A. Persistence of human immunodeficiency virus (HIV) type 1 DNA in peripheral blood despite prolonged suppression of plasma HIV-1 RNA in children. J. Infect. Dis. 2002; 185(10): 1409-16. https://doi.org/10.1086/340614
  22. Hoen B., Cooper D.A., Lampe F.C., Perrin L., Clumeck N., Phillips A. N., QUEST Study Group. Predictors of virological outcome and safety in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PR0B3005. Clin. Infect. Dis. 2007; 45(3): 381-90. https://doi.org/10.1086/519428
  23. Ngo-Giang-Huong N., Deveau C., Da Silva I., Pellegrin I., Venet A., Harzic M., French PRIMO Cohort Study Group. Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy. AIDS 2001; 15(6): 665-73.
  24. Tsiara C.G., Nikolopoulos G.K., Bagos P. G., Goujard C., Katzenstein T.L., Minga A.K., Hatzakis A. Impact of HIV type 1 DNA levels on spontaneous disease progression: a meta-analysis. AIDS Research and Human Retroviruses 2012; 28(4): 366-73. https://doi.org/10.1089/aid.2011.0032
  25. Goujard C., Bonarek M., Meyer L., Bonnet F., Chaix M.L., Deveau C., Agence Nationale de Recherche sur le Sida PRIMO Study Group. CD4+ cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients. Clin. Infect. Dis. 2006; 42(5): 709-15. https://doi.org/10.1086/500213

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2021 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies