Inflammatory markers in HIV-infected patients initiating antiretroviral therapy with modern regimes
Objective. Evaluation of the dynamics of key markers of systemic inflammation in treatment-naive patients with HIV infection receiving a two-drug antiretroviral therapy (ART) regimen of dolutegravir + lamivudine (DTG + 3TC) compared to a three-drug regimen (DTG + 3TC + TDF).Efanova A.A., Kanestri V.G., Khokhlova O.N., Pokrovskaya A.V., Kulabukhova E.I., Goliusova M.D., Shakhgildyan V.I., Efremova O.S., Popova A.A., Andreev A.V., Kozyrina N.V., Kravchenko A.V., Yurin O.G.
Materials and methods. This prospective observational study included 65 ART-naive patients (45 initiated therapy with the DTG + 3TC regimen, 20 with the DTG + 3TC + TDF regimen). The groups were comparable in terms of key demographic and clinical laboratory parameters. C-reactive protein (CRP), sCD163, interleukin (IL) IL-6, IL-8, IL-10, interferon (IFN) α, IFN-γ, and MIP-1α levels were determined at baseline and at weeks 24 and 48 of ART using a highly sensitive ELISA method.
Results. In the DTG + 3TC group, after 48 weeks of therapy, a statistically significant decrease in the median levels of CRP (from 0.2 to 0.1 mg/L; p=0.0022), sCD163 (by 30%; p < 0.001), IL-6 (by 68%; p=0.002), and IL-10 (by 30%; p=0.054) was achieved. The proportion of patients with elevated CRP levels decreased from 25.7% to 8.6% (p < 0.05), while IL-6 decreased from 32.5% to 24.2% (p = 0.018). No significant intergroup differences in the studied markers were observed in the triple therapy group at week 24. Complete suppression of viral replication was the primary requirement for a significant reduction in IL-6 and IL-10 levels.
Conclusion. The DTG + 3TC regimen in previously untreated HIV-infected patients provides a rapid, significant, and sustained reduction in key markers of systemic inflammation, comparable to the triple therapy. Baseline immunodeficiency and high viral load may delay the normalization of individual cytokine levels but do not impede the anti-inflammatory effect provided HIV is effectively suppressed. Past bacterial infections do not reduce the rate of inflammation regression during ART. The key factor in reducing chronic immune inflammation is achieving undetectable HIV RNA levels, regardless of the chosen ART regimen.
Keywords
HIV infection
antiretroviral therapy
inflammatory markers
dolutegravir
lamivudine
cytokines
References
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About the Authors
Anastasia A. Efanova, Postgraduate Student, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; kolman.nastasya98@mail.ru; https://orcid.org/0009-0008-3928-7201Veronika G. Kanestry, MD, Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; kanestri@yandex.ru; http://orcid.org/0000-0002-2234-7094
Olga N. Khokhlova, Cand. Med. Sci., Head, Clinical and Laboratory Group of the CDD of AIDS: Doctor of Clinical Laboratory Physician, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; xoxlova@cmd.su; https://orcid.org/0000-0001-9736-4043
Anastasia V. Pokrovskaya, MD, Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Professor; Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute, RUDN University,, Moscow, Russia; pokrovskaya_av@mail.ru; http://orcid.org/0000-0002-2677-0404
Ekaterina I. Kulabuhova, Cand. Med. Sci., Infectiologist, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Head, Laboratory of the Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute, RUDN University, Moscow, Russia; ekulabukhova@mail.ru; http://orcid.org/0000-0003-3645-7275
Marina D. Goliusova, Infectiologist, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; mad2501@yandex.ru; https://orcid.org/0000-0002-5325-6857
Vasiliy I. Shakhgildyan, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; vishakh@yandex.ru; htpp://orcid.org/0000-0002-8686-0487
Oksana S. Efremova, Cand. Med. Sci., Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; ks517@yandex.ru; https://orcid.org/0000-0001-5037-4041
Anna A. Popova, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Associate Professor, Department of Infectious Diseases, Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russia, Moscow, Russia; asya-med@mail.ru; https://orcid.org/0000-0001-9484-5917
Alexandr V. Andreev, Infectiologist, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; dr.ava@list.ru; https://orcid.org/0009-0006-1133-733x
Nadezhda V. Kozyrina, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; nad-kozyrina@yandex.ru; htpp://orcid.org/0000-0001-5134-0054
Professor Alexey V. Kravchenko, МD, Leader Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; alexey-kravtchenko@yandex.ru; http://orcid.org/0000-0001-7857-3763
Oleg G. Yurin, МD, Leading Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; htpp://orcid.org/0000-0003-1930-7486
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