Русский
Markers for systemic inflammation in HIV-infected patients with different blood HIV RNA levels: diagnostic significance and comparative analysis
DOI: https://dx.doi.org/10.18565/epidem.2018.4.56-62
Matuzkova A.N., Pshenichnaya N.Yu., Suladze A.G., Dosyagaeva L.I., Tverdokhlebova T.I.
1 Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; 2 Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don, Russia
Materials and methods. The investigation enrolled 224 HIV-infected patients who were divided into 3 main groups according to the level of HIV replication. The serum content of lipopolysaccharide-binding protein (LBP), procalcitonin, and cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, INF-γ, and INF-α) was estimated by solid-phase enzyme immunoassay. The plasma concentration of HIV RNA was determined by real-time PCR.
Results. The mean concentrations of LBP and cytokines were significantly higher in all the patients than in the healthy individuals. There was a moderate correlation between the blood levels of HIV viral load and LBP in the groups of patients with a definable HIV replication level.
The HIV-infected patients with HIV viremia were observed to have signs of more active systemic inflammation accompanied by the enhanced production of anti-endotoxin protein and cytokines (TNF-a, IL-10, INF-α, and INF-γ) compared with the patients with an undetectable level of HIV viral load.
Conclusion. Antiretroviral therapy can substantially reduce the severity of systemic inflammation in patients with HIV infection, but there is no normalization in anti-endotoxin protein concentrations and cytokine status indicators even during effective treatment.
Literature
1. Jinbiao L., Qianhao X., Runhong Z., Yong W., Qiaoyang X. et al. Comparative analysis of immune activation markers of CD8+ T cells in lymph nodes of different origins in SIV-infected chinese rhesus macaques. Frontiers in Immunology 2016; (7): 371. DOI: 10,3389/fimmu.2016.00371 2. Tien P.C., Choi A.I., Zolopa A.R., Benson C., Tracy R., Scherzer R. et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. Journal of Acquired Immune Deficiency Syndromes. 2010; 55 (3): 316–22. DOI: 10.1097/QAI.0b013e3181e66216. 3. Paiardini M., Müller-Trutwin M. HIV-associated chronic immune activation. Immunological Reviews 2013; 254 (1): 78–101. DOI: 10.1111/imr.12079. 4. Miedema F., Hazenberg M.D., Tesselaar K., van Baarle D., de Boer R.J. et al. Immune activation and collateral damage in AIDS pathogenesis. Frontiers in Immunology 2013; (4): 298. DOI: 10.3389/fimmu.2013.00298 · 5. Rajasuriar R., Wright E., Lewin S. Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage. Current Opinion in HIV and AIDS 2015; 10(1): 35. DOI: 10.1097/COH.0000000000000118. 6. Lichtfuss G.F., Hoy J., Rajasuriar R., Kramski M., Crowe S., Lewin Sh. Biomarkers of immune dysfunction following combination antiretroviral therapy for HIV infection. Biomarkers in Medicine 2011; 5(2): 171–86. 7. Brenchley J.M., Schacker T.W., Ruff L.E., Price D.A., Taylor J.H., Beilman G.J. et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. Journal of Experimental Medicine 2004; 200(6): 749–59. 8. Li Q., Duan L., Estes J.D., Ma Z.M., Rourke T., Wang Y. et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005; 434(7037): 1148–52. DOI: 10.1038/nature03513 9. Хасанова Г.Р., Биккинина О.И., Анохин В.А., Халиуллина C.В., Яковлев М.Ю. Кишечный эндотоксин как вероятный индуктор системного воспалительного ответа при ВИЧ-инфекции. Практическая медицина 2012; (56): 52–5. Khasanova G. R., Bikkinina O. I., Anokhin V. A., Khaliullina C. V., Yakovlev M. Yu. [Intestinal endotoxin as a probable inducer of systemic inflammatory response in HIV infection]. Prakticheskaуa meditsina 2012; (56): 52–5. (In Russ.). 10. Wada N.I., Jacobson L.P., Margolick J.B., Breen E.C., Macatangay B., Penugonda S. et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS 2015; 29: 463–471. DOI: 10.1097/QAD.0000000000000545. 11. Pelsers M.M, Namiot Z. Kisielewski W., Namiot A., Januszkiewicz M., Hermens W.T. et al. Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Clinical Вiochemistry 2003; 36: 529–35. DOI:10.1016/S0009-9120(03)00096-1 12. Sandler N.G., Wand H., Roque A., Law M., Nason M.C., Nixon D.E. et al., INSIGHT SMART Study Group 2011. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J. Infect. Dis. 2011; 203(6): 780–90. DOI: 10.1093/infdis/jiq118 13. Mavigner M., Cazabat M., Dubois M., L’Faqihi F.E., Requena M., Pasquier C. et al. Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. The Journal of Сlinical Investigation 2012; 122(1): 62–9. https://doi.org/10.1172/JCI59011. 14. Reus S., Portilla J., Sánchez-Payá J., Giner L., Francés R., Such J. et al. Low-level HIV viremia is associated with microbial translocation and inflammation. Journal of Acquired Immune Deficiency Syndromes: JAIDS 2013; 62(2): 129–34. DOI: 10.1097/QAI.0b013e3182745ab0. 15. Falasca F., Di Carlo D., De Vito C., Bon I., d’Ettorre G., Fantauzzi A. et al. Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns. BMC Infect. Dis. 2017; 17(1): 581. DOI: 10.1186/s12879-017-2676-2. 16. Sauce D., Fastenackels S., Pauchard M., Ait-Mohand H., Schneider L. et al. HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis. Blood 2011; 117(19): 5142–51. 17. Hunt P.W., Hunt P.W., Brenchley J., Sinclair E., McCune J .M., Roland M., Page-Shafer K. et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J. Infect. Dis. 2008; 197(1): 126–33. DOI: 10.1086/524143 18. Neuhaus J., Jacobs D.R., Jr. Baker J.V., Calmy A., Duprez D., La Rosa A. et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J. Infect. Dis. 2010; 201(12): 1788–795. DOI: 10.1086/652749. 19. Deeks S.G. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Topics in HIV medicine: a publication of the International AIDS Society, USA. 2009; 17(4): 118–23. 20. Bastard J.P., Soulié C., Fellahi S., Haïm-Boukobza S., Simon A., Katlama C. et al. Circulating interleukin-6 levels correlate with residual HIV viraemia and markers of immune dysfunction in treatment-controlled HIV-infected patients. Antiviral Therapy 2012; 17: 915–19. DOI: 10.3851/IMP2093 21. Borges Á.H., Silverberg M.J., Wentworth D., Grulich A.E., Fätkenheuer G., Mitsuyasu R. et al. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers. AIDS 2013; 27(9): 1433–41. DOI: 10.1097/QAD.0b013e32835f6b0c 22. Grund B., Baker J.V., Deeks S.G., Wolfson J., Wentworth D., Cozzi-Lepri A. et al. Relevance of interleukin-6 and D-dimer for serious non-AIDS morbidity and death among HIV-positive adults on suppressive antiretroviral therapy. PLoS One 2016; 11(5). DOI:10.1371/journal.pone.0155100. 23. d’Ettorre G., Ceccarelli G., Pavone P., Vittozzi P., De Girolamo G., Schietroma I. et al. What happens to cardiovascular system behind the undetectable level of HIV viremia? AIDS Research and Therapу 2016; 13(1): 21. DOI: 10.1186/s12981-016-0105-z. 24. Ploquin M.J., Silvestri G., Müller-Trutwin M. Immune activation in HIV infection: what can the natural hosts of SIV teach us? Current Opinion in HIV and AIDS 2016; 11(2): 201–8. For citations: Matuzkova A.N., Pshenichnaya N.Yu., Suladze A.G., Dosyagaeva L.I., Tverdokhlebova T.I. Markers for systemic inflammation in HIV-infected patients with different blood HIV RNA levels: diagnostic significance and comparative analysis. Èpidemiologiâ i infekcionnye bolezni. Аktual’nye voprosy 2018; (4):56–62 (In Russ.).
About the Autors
Anna N. Matuzkova, Infectiologist, Polyclinic Department, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being,
Rostov-on-Don, Russia; е-mail: matuzkova@yandex.ru; ORCID: http://orcid.org/0000-0002-5980-3436
Prof. Natalia Yu. Pshenichnaya, MD, Head, Infectious Diseases Department with Course of Childhood Infectious Diseases, Faculty for Advanced Training and Professional Retraining of Specialists, Rostov State Medical University, Ministry of Health of Russia; Infectiologist, Infectious Diseases and Parasitology Clinic, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: natalia-pshenichnaya@yandex.ru; ORCID: http://orcid.org/ 0000-0003-2570-711X
Aleksandr G. Suladze, Can. Med. Sci.; Head, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: hivrost@mail.ru; ORCID: http://orcid.org/0000-0002-9051-1220
Ludmila I. Dosyagaeva, Virologist, Clinical and Diagnostic Laboratory, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: hivrost@mail.ru; ORCID: http://orcid.org/ 0000-0003-3715-0662
Tatiana I. Tverdokhlebova MD; Director, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: niimicrodouble@yandex.ru; ORCID: http://orcid.org/0000-0002-4280-6702
Similar Articles
