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1. Markers of CD4⁺ AND CD8⁺ T-cell exhaustion in hiv/hcv coinfected immunological non-responders to antiretroviral therapy

Author

Evgeniya V. Saidakova, L. B. Korolevskaya, V. V. Vlasova, N. G. Shmagel, and K. V. Shmagel

Subjects
hiv/hcv coinfection, antiretroviral therapy, immunological non-response, t-lymphocytes, exhaustion, pd-1, proliferation, cell death, interleukin-2, Infectious and parasitic diseases, RC109-216
Abstract

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a risk factor for immunological non-response to antiretroviral therapy. In cases of immunological non-response, HIV viral load suppression occurs without an increase in CD4⁺ T-cell counts, heightening the risk of morbidity and mortality in infected individuals. T-cell exhaustion may hinder their regeneration in immunological non-responders. This study aimed to identify markers of CD4⁺ and CD8⁺ T-cell exhaustion in HIV/HCV coinfected immunological non-responders. The study examined three clinical groups: 1) HIV/HCV coinfected immunological non-responders (CD4⁺ T-cells 350/µl blood; n = 9), 2) HIV/HCV coinfected individuals with a standard response to therapy (CD4⁺ T-cells 500/µl blood; n = 9), and 3) relatively healthy volunteers without HIV and HCV infections (n = 9). Ex vivo, the number of CD4⁺ and CD8⁺ T-cells expressing the inhibitory receptor PD-1 was determined using multi-color flow cytometry. In the 7-day in vitro experiment, cell cultures were stimulated with phytohemagglutinin. The number of dying proliferated CD4⁺ and CD8⁺ T-cells (CFSElowZombieUV+) was determined using multi-color flow cytometry. The amount of interleukin-2 in the culture supernatants was measured using an enzyme-linked immunosorbent assay. It was found that in HIV/HCV coinfected immunological non-responders, there was a higher number of CD4⁺ and CD8⁺ T-cells expressing PD-1, a phenotypic marker of exhaustion, compared to the other two groups. Furthermore, the frequency of dying dividing T-cells was higher in immunological non-responders, with an increase in CD4⁺ T-cells but not CD8⁺ T-lymphocytes. Similarly, a decrease in interleukin-2 production was found in stimulated T-cells of HIV/HCV coinfected immunological non-responders in the CD4⁺ T-cell pool, but not in CD8⁺ T-lymphocytes. Thus, in HIV/HCV coinfected immunological non-responders, CD4⁺ T-cells appear exhausted both phenotypically and functionally. While CD8⁺ T-cells express inhibitory receptors, they do not show functional impairments. It appears that the specialized therapy for HIV/HCV coinfected immunological non-responders should aim to improve CD4⁺ T-cell function.

Published
2024
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2. Functional exhaustion of CD4+T cells in HIV/HCV coinfected HAART-treated patients

Author

V. V. Vlasova, L. B. Korolevskaya, O. A. Loginova, N. G. Shmagel, and E. V. Saidakova

Subjects
hiv-infection, hepatitis c, cd4+t cells, immune activation, immune exhaustion, cytokine production, Immunologic diseases. Allergy, RC581-607
Abstract

Infection with hepatitis C virus (HCV) is common among HIV-positive patients, with up to 50% of them being coinfected in Russia. While highly active antiretroviral therapy (HAART) suppresses HIV replication and restores the immune system of HIV-infected subjects, HCV coinfection interferes with CD4+T cell regeneration and increases the risk of patients’ morbidity and mortality. During HAART, HIVinfection progression and the immune system restoration efficiency largely depend on immune activation and CD4+T cell exhaustion. This study determined the level of activation, exhaustion, and cytokine production in CD4+T cells obtained from the peripheral blood of HAART-treated HIV/HCV coinfected and HIV monoinfected subjects. The study comprised 11 HIV/HCV coinfected individuals and 10 HIV monoinfected patients receiving HAART for more than two years, with a control group of 10 volunteers without the signs of HIV or HCV infections. Compared with healthy controls, HIV/HCV coinfected patients had an increased frequency of activated CD38+HLA-DR+ CD4+T lymphocytes (p < 0.05), a higher level of CD4+T cell exhaustion determined according to the TIGIT expression density per cell (p < 0.05), and a greater proportion of interferon-gamma (IFNγ)-producing CD4+T lymphocytes following activation (p < 0.05). The frequency of IFNγ-producing CD4+T cells in the donors’ blood positively correlated with the proportion of activated CD4+T cells (R = 0.514, p < 0.01). Despite having a large number of IFNγ-producing CD4+T lymphocytes, the HIV/HCV coinfected patients’ average production of IFNγ by CD4+T cells was significantly lower than that in healthy controls (p < 0.05). The IFNγ production in CD4+T lymphocytes did not depend on activation (p > 0.05). However, a negative correlation was established between the IFNγ production and the level of CD4+T cell exhaustion (R = -0.400, p < 0.05). The letter was also found to inversely correlate with the CD4+T cell counts in the donors’ peripheral blood (R = -0.598, p < 0.01). These data suggest that HCV coinfection leads to pronounced functional exhaustion of CD4+T cells and may aggravate the course of HIVinfection in patients receiving HAART.

Published
2023
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3. In HIV-infected patients, intestinal bacteria-derived products interfere with CD4+T cell regeneration

Author

L. B. Korolevskaya, E. V. Saidakova, N. G. Shmagel, and K. V. Shmagel

Subjects
hiv infection, bacterial toxins, intestine, cd4+t lymphocytes, antiretroviral therapy, immune regeneration, Immunologic diseases. Allergy, RC581-607
Abstract

Despite successful suppression of viral replication by antiretroviral drugs there is no significant increase in the number of peripheral CD4+T lymphocytes in some HIV-infected patients (immune nonresponse to therapy). One of the crucial factors for immunodeficiency aggravation is immune activation developing in response to the bacterial products entry into the bloodstream through the damaged intestinal barrier. Additionally, the intestinal microflora produces various solutes that accumulate in the blood and exhibit toxic properties. This work aimed to evaluate the effect of intestinal microbial products (para-cresol sulfate and indoxyl sulfate) on the number of CD4+T lymphocytes in HIV-infected patients receiving antiretroviral therapy. The object of the study was the peripheral blood of HIV-infected subjects with different immune system restoration efficiency during the therapy. Uninfected donors were enrolled as healthy controls. Plasma concentrations of IL-6 (p = 0.012), IP-10 (p = 0.0004), and sCD14 (p = 0.003) in HIV-infected immune nonresponders were increased compared with those in individuals with effective restoration of CD4+Tcells (immune responders). Although both groups of HIV-positive subjects did not differ in plasma lipopolysaccharide and I-FABP levels, para-cresol sulfate (p = 0.001) and indoxyl sulfate (p = 0.042) concentrations were increased in immune non-responders. In vitro experiments showed a negative dose-dependent effect of para-cresol sulfate and indoxyl sulfate on the viability and mitotic activity of CD4+T lymphocytes. Thus, in HIV-infected patients with impaired regeneration of CD4+T lymphocytes during antiretroviral therapy, a higher level of systemic inflammation is noted than in subjects responding to treatment with an increase in the number of CD4+T cells. The severity of the intestinal barrier damage and the load of bacterial components released into the bloodstream are approximately the same in HIV-infected individuals with different efficiency of immune recovery in response to treatment. Simultaneously, the blood plasma of immune non-responders is significantly enriched with microbial products of intestinal origin: para-cresol sulfate and indoxyl sulfate. The significant decrease in the proliferative capacity of CD4+T cells stimulated in vitro and the induction of their death in the presence of these toxins may be a reason for the ineffective restoration of the number of CD4+T lymphocytes in HIV-infected individuals receiving antiretroviral therapy.

Published
2023
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4. Metabolic features of naïve and memory CD4+T cells in quiescence and during proliferation

Author

V. V. Vlasova, E. V. Saidakova, L. B. Korolevskaya, N. G. Shmagel, and K. V. Shmagel

Subjects
cd4+ t lymphocytes, memory t cells, naive t cells, glucose, fatty acids, glutamine, mitochondria, proliferation, Science
Abstract

Background. Memory CD4+ T cells proliferation is the basis for accelerated secondary immune response. The characteristics of memory CD4+ T cells providing their faster division compared to naive CD4+ T lymphocytes are poorly understood. T cells proliferative ability is determined by their metabolism. The metabolic features of proliferating memory CD4+ T cells remain elusive. The aim. To compare the metabolic features of naive and memory CD4+ T cells in quiescence and during proliferation. Methods. Peripheral blood mononuclear cells were analyzed using flow cytometry. Dividing cells were identified by CD71 expression. Cellular glucose and fatty acid uptake was assessed using fluorescent glucose (2-NBDG) and palmitate (BODIPY-FL-C16) analogs, respectively. Glutamine transporter expression was analyzed by staining the cells with anti-ASCT2 antibodies. Mitochondrial mass and membrane potential were measured using MitoTracker Green and MitoTracker Orange, respectively. Results. Quiescent memory CD4+ T cells exhibited elevated levels of glucose and palmitate uptake when compared to naive CD4 + T lymphocytes (p < 0.001). Both subsets had increased substrate consumption when proceeding to proliferation (p < 0.001). When dividing, naive CD4+ T cells consumed more glucose and palmitate than memory CD4+ T cell (p < 0.001). Proliferation caused an increase in mitochondrial mass in naive (p < 0.001) and memory CD4+ T lymphocytes (p < 0.05). In memory CD4+ T cells, unlike naive CD4+ T lymphocytes, an increase in mitochondrial mass wasn’t accompanied by an increase in membrane potential. Conclusion. In memory CD4 + T cells, compared to naive CD4+ T lymphocytes, the metabolic change induced by proliferation is moderate and affects the mitochondrial activity to a lesser extent. Lower bioenergetic expenses of memory CD4+ T cells can contribute to their rapid proliferation during secondary immune response.

Published
2022
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5. Regulatory T cell subsets in peripheral blood of HIV-infected patients with discordant response to antiretroviral therapy

Author

L. B. Korolevskaya, E. V. Saidakova, N. G. Shmagel, and K. V. Shmagel

Subjects
hiv-infection, antiretroviral therapy, discordant immunological response, regulatory t cells, naive t lymphocytes, central memory t cells, effector memory t cells, Immunologic diseases. Allergy, RC581-607
Abstract

The discordant immunologic response to antiretroviral therapy in HIV-infected patients is characterized by ineffective recovery of CD4+T cell counts. The role of regulatory T cells in discordant response to the treatment remains poorly understood both due to the lack of specific and reliable markers of regulatory T cells and their subset’s heterogeneity. In the present work, we studied two groups of HIV-infected patients receiving antiretroviral therapy for more than two years and thus having their viral load suppressed (less than 50 copies of HIV per ml of blood): those who responded (n = 22) and did not respond (n = 19) to the treatment with an increase in their CD4+T cell counts. The control group consisted of uninfected volunteers (n = 23). The CD4+T lymphocyte subset composition was examined by flow cytometry. It was shown that in HIV-infected patients with ineffective immune recovery compared with subjects having a standard response to antiretroviral therapy, the absolute counts of regulatory T cells, as well as CD4+T lymphocytes, was reduced in all maturational subsets: naive cells, central memory, effector memory, and terminally differentiated effectors. That differed immunological nonresponders from patients with a standard response to the treatment, which had a shortage only in naive and central memory regulatory T cell subsets. It is important to note that in HIV-infected patients with a discordant response to therapy, the proportion of effector memory regulatory T cells, that posses the most prominent suppressive capacity, was significantly increased compared with that in other CD4+T lymphocyte subsets. Apparently, despite of regulatory T cell deficiency, in HIV-infected patients with a discordant response to the treatment, the regulatory T cell pool size is big enough to control CD4+T lymphocyte activation. Nevertheless, the number of regulatory T cells may not be sufficient to suppress the over-activation of immunocompetent cells that are not in the CD4+T lymphocyte subset. This can partly explain the increased cell activation level in patients with a discordant response to therapy as compared with those who have a standard respond to the treatment.

Published
2020
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6. Regulatory T-lymphocyte subsets in patients with HIV-infection receiving highly active antiretroviral therapy

Author

V. A. Chereshnev, E. V. Saidakova, L. B. Korolevskaya, N. G. Shmagel, and K. V. Shmagel

Subjects
вич-инфекция, антиретровирусная терапия, cd4+ т-лимфоциты, иммунная активация, регуляторные т-кле, Medicine
Abstract

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection.

Published
2019
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7. IMMUNITY ACTIVATION IN HIV INFECTION

Author

K. V. Shmagel, N. G. Shmagel, and V. A. Chereshnev

Subjects
hiv infection, immune activation, inflammation, lymphopenia, cytokines, microbial translocation, Immunologic diseases. Allergy, RC581-607
Abstract

This review article concerns a challenging problem of HIV infection, immune activation. The processes of immune activation largely determine CD4+T cell depletion, leading to development of AIDS-associated and non-AIDS-related diseases. Immune activation indices are also strong predictors of the clinical outcome. Activation in HIV-infection affects both innate and adaptive immune cells, leads to increased proinflammatory cytokine production and blood coagulation. The reasons for immune activation may include different pathogens (HIV, cytomegalovirus, Epstein–Barr virus, hepatitis C virus), lymphopenia and lymphopenia-induced T lymphocyte homeostatic proliferation, transfer of microbial products from the gut, due to profound CD4+T cell deficiency in lamina propria and altered permeability of intestinal barrier. Other factors that promote the process of immune activation are as follows: T lymphocyte "bystander" activation, increased T cell turnover, and systemic inflammation development. The review covers pathogenic mechanisms HIV-infection associated with immune activation, like as description of different laboratory parameters characterizing its manifestations in HIV-infected patients. Significance and prognostic role of these parameters in assessing efficiency of antiretroviral therapy, development of complications, and adverse outcomes of infection are presented as well.

Published
2017
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8. ROLE OF HEPATITIS C VIRUS COINFECTION IN VIOLATION OF PRODUCTIVE THYMIC FUNCTION IN HIV-INFECTED PATIENTS UNDER IMMUNOLOGICALLY INEFFICIENT ANTIRETROVIRAL THERAPY

Author

E. V. Saidakova, L. B. Korolevskaya, N. G. Shmagel, K. V. Shmagel, and V. A. Chereshnev

Subjects
hiv/hcv-coinfection, antiretroviral therapy, immunological areactivity, apoptosis, thymic productive function, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract. The role of hepatitis C virus (HCV) co-infection in violation of restoring CD4+T cells in HIVinfected patients receiving antiretroviral therapy (ART) was investigated. Seventy eight patients with effective virological response to ART (viral load < 50 copies/ml) who either had or had no good immunological CD4+Tcell response after two years of treatment were recruited. Twenty one relatively healthy volunteers served as controls. The numbers of main T-lymphocyte populations and their apoptosis rates were determined. Thymus productive function was assessed by the number of αTREC-positive CD4+ and CD8+T cells. It is shown that HIV/HCV co-infection is characterized by lower numbers of CD4+T-lymphocytes in patients’ blood compared with HIV-monoinfection. This is not associated with the cells’ increased death rates. We also demonstrate that HCV coinfection reduces the production of CD4+, but not CD8+T-lymphocytes, by the thymus.

Published
2014
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10. Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus

Author

K V Shmagel, N G Shmagel, L B Korolevskaya, E V Saydakova, and V A Chereshnev

Subjects
hiv/hcv coinfection, antiretroviral therapy, activation of immunity, proliferation, destruction of the intestinal barrier, Medicine
Abstract

Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.

Published
2016
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12. PGC-1α in human CD4+T cell subsets

Author

V. V. Vlasova and N. G. Shmagel

Subjects
Immunology, General Medicine
Abstract

CD4+T lymphocyte pool is heterogeneous in nature consisting of distinct subsets. The functional activity of each subset is highly influenced by how its energy metabolism is controlled. In naïve, central memory, effector memory, and TEMRA CD4+T cells received from healthy volunteers aged 29-42 years we evaluated the level of the major cell energy metabolism regulator: transcriptional coactivator PGC-1α. PGC-1α was shown to be expressed in all CD4+T cells. Its level in central memory, effector memory, and TEMRA cells was higher than that in naïve cells for both conventional and regulatory CD4+T lymphocytes. Moreover, its level was found to be higher in conventional when compared with regulatory CD4+T cells. Our findings suggest that regulatory and conventional CD4+T cells rely on PGC-1α to a different extent. Apparently, PGC-1α is an important but not the only factor influencing the functional state of mitochondria in regulatory CD4+T lymphocytes.

Published
2020

13. Changes in the regulatory T-lymphocyte counts in HIV-infected patients with a discordant response to antiretroviral therapy

Author

N. G. Shmagel, K. V. Shmagel, E. V. Saidakova, L. B. Korolevskaya, and V. A. Chereshnev

Subjects
Adult, Male, Anti-HIV Agents, T cell, Regulatory T-Lymphocytes, HIV Infections, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology, Immune system, Medicine, Hiv infected patients, Humans, Immunodeficiency, Multidisciplinary, General Immunology and Microbiology, business.industry, General Medicine, T lymphocyte, medicine.disease, Antiretroviral therapy, CD4 Lymphocyte Count, medicine.anatomical_structure, Immunology, T cell subset, Female, General Agricultural and Biological Sciences, business
Abstract

We examined HIV‑infected patients with different efficiency of immune system restoration during the course of antiretroviral therapy. The study showed that against the background of low CD4+ T‑cell counts, subject with a discordant immunologic response (patients with less than 350 CD4+ T‑cells per µl of blood after more than two years of treatment) develop a regulatory CD4+ T‑cell (Treg) deficiency. Furthermore, in these patients, the immunodeficiency is accompanied by an increase in the Treg frequency. Accumulation of regulatory T‑cells in the blood of HIV‑infected subjects with discordant response to the treatment indicates a high viability of this T‑cell subset.

Published
2019

14. Morphological characteristic of inguinal lymph nodes in HIV infection

Author

N. G. Shmagel, G. G. Freind, L. B. Korolevskaya, K. V. Shmagel, Evgeniya V. Saidakova, and N. I. Gulyaeva

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Stromal cell, business.industry, H&E stain, Hilum (biology), Staining, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Reticular cell, 030220 oncology & carcinogenesis, medicine, Immunohistochemistry, Lymph, business, Lymph node
Abstract

Aim. To assess the morphological changes in inguinal lymph nodes among patients with stage 4a HIV infection, who receive antiretroviral therapy. Materials and methods. There were examined 12 HIV-infected patients with stage 4a, treated at “Perm Regional Center for Prevention and Fight against AIDS and Infectious Diseases”, who received antiretroviral therapy for 2 years. Two groups of patients were formed: group I – 6 persons, whose CD+ blood lymphocyte number was more than 350 in 1 mcl; group II – 6 persons with CD+ blood lymphocyte number less than 350 in 1 mcl. Inguinal lymph nodes (ILN) were taken under local anesthesia, histological preparations were prepared by traditional scheme, stained with hematoxylin and eosin using Masson three-colour staining. In immunohistochemical reactions expression of Ki-67 and CD+ markers was estimated. Results.Histoarchitectonics of lymph nodes was changed as a result of massive development of sclerosis in the region of hilum, capsule and trabecules. Against the background of sclerosis, there occurred lymphocyte depletion, change in structure of stromal cells and neoangiogenesis in all the zones of the lymph node. In the regions of sclerosis, death of lymphocytes was revealed. In patients of the second group, more active development of follicles with the centers of reproduction in the lymph node cortical substance, as well as growth of the number of Ki-67 maker-expressing cells was established Conclusions.In the inguinal lymph nodes, the development of sclerotic processes causes the death of T-lymphocytes, which, in their turn, are the source of lymphotoxin-β formation. Loss of CD+-T-lymphocytes is accompanied by deficit of lymphotoxin-β and induces the loss of fibroblastic reticular cells themselves, which through the production of IL-7 support the vital activity of T-cells.

Published
2019

15. CD4+ T-Cell Cycling in HIV-Infected Patients with the Discordant Immunologic Response to the Antiretroviral Therapy

Author

L. B. Korolevskaya, N. G. Shmagel, K. V. Shmagel, S. V. Yuzhaninova, N. I. Gulyaeva, E. V. Saidakova, G. G. Freund, and V. A. Chereshnev

Subjects
0301 basic medicine, 030102 biochemistry & molecular biology, Cell growth, T cell, Cell Biology, T lymphocyte, Biology, In vitro, Peripheral, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Immune system, Viral replication, Immunology, medicine, Lymph
Abstract

Discordant immune response to antiretroviral therapy (ART) in HIV infection is characterized by insufficient reconstitution of peripheral CD4+ T lymphocyte numbers despite suppression of virus replication. The causes of inefficient regeneration of CD4+ T cells on ART remain elusive. The paper reports the study involving two groups of HIV-positive patients: patients with discordant response to ART (n = 20) and patients with standard response to therapy (n = 21). The numbers of cycling (Ki-67+), senescent (CD57+), and exhausted (PD-1+) CD4+ T lymphocytes of varying degree of maturity have been determined in peripheral blood and lymph nodes of HIV-positive individuals. CD4+ T cell division asymmetry index after in vitro stimulation has been analyzed. Histological study of the lymph nodes of HIV-infected patients was carried out. It has been demonstrated that in the individuals with discordant immune response to ART, intensive CD4+ T cell cycling does not result in the increase in their count neither in peripheral blood, nor in the secondary lymphoid organs. At the same time, in the patients with impaired immune system recovery, increased cell proliferation is followed by the accumulation of exhausted CD4+ T lymphocytes. Moreover, patients with discordant immune response to ART revealed an asymmetric division of in vitro stimulated CD4+ T cells. The observed defects may be the cause of inefficient immune system recovery in HIV-infected patients on ART.

Published
2019

16. Characteristics of HIV patients in Eye Hospitals

Author

M.V. Chereshneva, T. V. Gavrilova, Valery A. Chereshnev, A. P. Sergienko, and N G Shmagel

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Hiv patients, Medicine, business
Published
2020

17. HCV coinfection of the HIV-infected patients with discordant CD4+ T-cell response to antiretroviral therapy leads to intense systemic inflammation

Author

Donald D. Anthony, E. V. Saidakova, Leonid Margolis, N. G. Shmagel, V. A. Chereshnev, K. V. Shmagel, L. B. Korolevskaya, and Michael M. Lederman

Subjects
Adult, CD4-Positive T-Lymphocytes, Lipopolysaccharides, Male, 0301 basic medicine, Lipopolysaccharide, Hepatitis C virus, T cell, HIV Infections, Systemic inflammation, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, Medicine, Hiv infected patients, General Immunology and Microbiology, Coinfection, business.industry, virus diseases, General Medicine, medicine.disease, Hepatitis C, Antiretroviral therapy, Systemic Inflammatory Response Syndrome, digestive system diseases, 030104 developmental biology, medicine.anatomical_structure, Anti-Retroviral Agents, Liver, chemistry, Immunology, Cytokines, Female, medicine.symptom, General Agricultural and Biological Sciences, business, 030215 immunology
Abstract

The level of proinflammatory markers was assessed in HIV-infected patients that were coinfected with hepatitis C virus (HCV) and had failed to restore the CD4+ T cell counts (immunological nonresponders, INR) during the antiretroviral therapy (ART). Among four patient groups (HIV+HCV− and HIV+HCV+ subjects with the concordant response to ART; HIV+HCV− and HIV+HCV+ subjects that were INR), the greatest systemic inflammation was in the latter group. The maximum difference was between the subjects HIV+HCV−INR and HIV+HCV+ INR: the blood of coinfected patients contained significantly higher concentrations of the IP-10, sCD163, sTNF-RI, and sTNF-RII and of bacterial lipopolysaccharide. Systemic inflammation in HIV/HCV coinfected patients with the discordant response to ART is probably caused by a breach of hepatic barrier for the intestine products.

Published
2017

18. [Ocular lesions in HIV-infected patients of the ophthalmic hospitals]

Author

N G Shmagel, M. V. Chereshneva, V. A. Chereshnev, T. V. Gavrilova, A. P. Sergienko, and E S Ivanova

Subjects
Adult, Male, medicine.medical_specialty, Tuberculosis, Eye Diseases, 030231 tropical medicine, Congenital cytomegalovirus infection, HIV Infections, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Internal medicine, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, Chlamydia, business.industry, Coinfection, HIV, Hepatitis B, medicine.disease, Toxoplasmosis, Ophthalmology, Syphilis, Female, business, Viral load
Abstract

To analyze ophthalmic pathologies in HIV-infected patients of the ophthalmic hospitals of Perm city.Medical records of 75 HIV patients registered in Perm Regional Centre for Prevention and Control of AIDS and Infectious Diseases who had received treatment in ophthalmic in-patient clinics of Perm in 2005-2015 years were analyzed retrospectively. Patient examination included traditional ophthalmological methods, as well as immunological (determination of CD4 cells and viral load), serological (detection of antibodies to herpes simplex virus, cytomegalovirus, chlamydia, toxoplasma), general clinical methods, and consultations by allied specialists.Ophthalmopathology requiring in-patient care was detected in 75 people (84 eyes). Men comprised 76%, women - 24%; average age was 32.82±8.68 years. The stage of HIV infection was known in 78.66% of patients: stage II - in 5% of cases, stage III - in 32%, stage IV - in 63%. Co-infection (hepatitis B and C, syphilis, tuberculosis) was detected in 81% of patients. HIV-related diseases (cytomegalovirus and herpes infection, candidiasis, toxoplasmosis) were observed in 48% of individuals. The time of emergence of ocular pathology from the time of HIV detection ranged from 1 day to 14 years. Inflammatory ocular diseases occurred in 55% of cases, dystrophic disorders - in 18%, eye traumas - in 24%, and strabismus - in 3% of patients. Reduced level of CD4 (less than 500 cells/mmAmong the studied individuals, eye lesion was mostly severe, inflammatory in nature; it occurred more frequently in stage IV HIV patients with reduced number of CD4 lymphocytes who was not receiving antiretroviral therapy.Цель - анализ глазной патологии у ВИЧ-инфицированных пациентов офтальмологических стационаров Перми. Материал и методы. Ретроспективно проанализированы данные медицинской документации 75 ВИЧ-инфицированных пациентов, находившихся на стационарном лечении в офтальмологических отделениях Перми и состоящих на учете в Пермском краевом центре по профилактике и борьбе со СПИДом за 2005-2015 гг. Обследование пациентов включало: традиционные офтальмологические методы, иммунологические (определение CD4-клеток и вирусной нагрузки), серологические (выявление антител к вирусу простого герпеса, цитомегаловирусу, хламидиям, токсоплазме), общеклинические методы, консультации смежных специалистов. Результаты. Среди 75 пациентов с глазной патологией, выявленной на 84 глазах и требующей лечения в стационаре, мужчин было 76%, женщин - 24%; средний возраст составлял 32,82±8,68 года. Стадия ВИЧ-инфекции известна у 78,66% пациентов: II - в 5% случаев, III - в 32%, IV - в 63%. Коинфекция (гепатит В и С, сифилис, туберкулез) имела место у 81% пациентов. ВИЧ-ассоциированные заболевания (цитомегаловирусная и герпесная инфекции, кандидоз, токсоплазмоз) установлены у 48% лиц. Время появления глазной патологии от момента выявления ВИЧ-инфицирования колебалось от 1 дня до 14 лет. Воспалительные заболевания органа зрения встречались в 55% наблюдений, дистрофические - в 18%, травмы - в 24%, косоглазие - в 3%. Преобладали пациенты (72,13%) со сниженным уровнем CD4-клеток (менее 500 кл/мм

Published
2019

19. Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis)

Author

Larisa B. Korolevskaya, Evgeniya V. Saidakova, N. G. Shmagel, and Konstantin V. Shmagel

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, medicine.medical_treatment, T cell, Antigen presentation, Antigen-Presenting Cells, HIV Infections, Antigen-Antibody Complex, Biology, Ligands, Lymphocyte Activation, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Humans, Antigen-presenting cell, Inflammation, Antigen Presentation, Macrophages, Lymphokine, General Medicine, Models, Theoretical, Th1 Cells, Acquired immune system, Immunity, Innate, Interleukin-10, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Immune System, Immunoglobulin G, Immunology, HIV-1, biology.protein, Cytokines, Antibody, 030215 immunology
Abstract

Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells.

Published
2016

20. CD8+ T cell expansion in HIV/HCV coinfection is associated with systemic inflammation

Author

K. V. Shmagel, L. B. Korolevskaya, V. A. Chereshnev, E. V. Saidakova, and N. G. Shmagel

Subjects
0301 basic medicine, General Immunology and Microbiology, T cell, Hepatitis C virus, virus diseases, Inflammation, General Medicine, Hepatitis C, Biology, medicine.disease, Systemic inflammation, medicine.disease_cause, 030112 virology, Virology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine.anatomical_structure, Immunology, medicine, Coinfection, Cytotoxic T cell, medicine.symptom, General Agricultural and Biological Sciences, CD8
Abstract

High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients is associated with increased peripheral CD8+ T cell counts. Hepatitis C virus (HCV) coinfection is an additional risk factor for the development of non-AIDS events. We found that, in HIV/HCV coinfection, the increased proportion of CD8+ T lymphocytes is due to the effector memory and terminal effector T cells gain. Moreover, in these patients, the accumulation of highly differentiated forms of CD8+ T lymphocytes was associated with increased concentrations of inflammatory indices.

Published
2017

21. Immune complexes that contain HIV antigens activate peripheral blood T cells

Author

L. B. Korolevskaya, V. A. Chereshnev, K. V. Shmagel, E. V. Saidakova, and N. G. Shmagel

Subjects
Male, 0301 basic medicine, T-Lymphocytes, Hepatitis C virus, Antigen-Antibody Complex, Antibodies, Viral, Lymphocyte Activation, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, Antigen, medicine, Humans, Antigens, Viral, Pan-T antigens, General Immunology and Microbiology, biology, virus diseases, General Medicine, Acquired immune system, Virology, In vitro, 030104 developmental biology, HIV Antigens, Immunology, HIV-1, biology.protein, Female, Antibody, General Agricultural and Biological Sciences
Abstract

Uninfected donor T cells were treated in vitro by model immune complexes that contained either HIV or hepatitis C virus (HCV) antigens. Unlike HCV antigen-containing complexes, the immune complexes that contained HIV antigens have been shown to activate peripheral blood T cells of uninfected donors under in vitro conditions. Both the antiviral antibodies and HIV antigen were involved in the activation process. The unique properties of the immune complexes formed by HIV antigens and antiviral antibodies are believed to result from the virus-specific antibody properties and molecular conformation of the antigen-antibody complex.

Published
2016

22. Effect of Hepatitis C Virus Coinfection on the Content of CD4+ and CD8+ T Cell Subpopulations in HIV-Infected Patients Receiving Antiretroviral Therapy

Author

N. G. Shmagel, L. B. Korolevskaya, V. A. Chereshnev, S. V. Slobodchikova, K. V. Shmagel, and E. V. Saidakova

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Anti-HIV Agents, viruses, T cell, Hepatitis C virus, HIV Infections, Thymus Gland, CD8-Positive T-Lymphocytes, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cytotoxic T cell, Hiv infected patients, 030212 general & internal medicine, Coinfection, business.industry, Case-control study, General Medicine, Hepatitis C, Chronic, medicine.disease, Antiretroviral therapy, Virology, 030104 developmental biology, medicine.anatomical_structure, Case-Control Studies, Female, Interferons, business, CD8
Abstract

We studied the effect of hepatitis C virus coinfection on T cell subpopulations in HIV-infected patients receiving antiretroviral therapy. Coinfection with hepatitis C virus was followed by a decrease in the number of naive CD4(+) T cells and an increase in the count of central CD8(+) memory T cells in these patients. Hepatitis C virus had no effect on the number of CD4(+) memory T cells (main target for HIV). This can explain the absence of strong negative effect of hepatitis C virus on the course of HIV infection.

Published
2016

23. Discordant response of CD4+ T cells to antiretroviral therapy in HIV-infected patients coinfected with hepatitis C virus is accompanied by increased liver damage

Author

Evgeniya V. Saidakova, Valery A. Chereshnev, N. G. Shmagel, Larisa B. Korolevskaya, and K. V. Shmagel

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Cirrhosis, Hepatitis C virus, Biophysics, medicine.disease_cause, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Interferon, Humans, Medicine, Hiv infected patients, 030212 general & internal medicine, Liver damage, Transaminases, Acquired Immunodeficiency Syndrome, business.industry, General Chemistry, General Medicine, Hepatitis C, medicine.disease, Antiretroviral therapy, Virology, Anti-Retroviral Agents, Liver, Immunology, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

A study of HIV-infected patients coinfected with hepatitis C virus and receiving antiretroviral therapy (ART) but not treated with interferon was performed. Patients were divided into two groups-with standard and inefficient recovery of CD4(+) T cells. It was found that patients with discordant response of CD4(+) T cells to ART showed heavier destructive processes in the liver than the successfully recovered subjects. They had increased levels of ALT and AST. In these patients, the risk of development of liver cirrhosis is greater.

Published
2015

24. Characteristics of Circulating Immune Complexes in HIV-Infected Patients with Different Viral Load

Author

L. B. Korolevskaya, K. V. Shmagel, and N. G. Shmagel

Subjects
HIV Antigens, HIV Infections, HIV Antibodies, General Biochemistry, Genetics and Molecular Biology, Immunoglobulin G, Immune system, Humans, Medicine, biology, business.industry, Case-control study, virus diseases, General Medicine, Viral Load, Virology, Titer, Immunoglobulin M, Case-Control Studies, Immunology, HIV-1, biology.protein, Antibody, business, Viral load
Abstract

Serum concentration of antiviral antibodies was measured in HIV-infected patients with different viral load. It was found that higher concentrations of HIV-antigens correspond to higher titer of antiviral antibodies. Circulating immune complexes were isolated from patients' serum to estimate their size and immunoglobulin composition. High levels of small IgG- and IgM-containing complexes were identified in HIV-infected patients. In patients receiving antiretroviral treatment, the content of these complexes was significantly lower than in patients with high HIV load. This attests to positive role of specific therapy in preventing immune complex-associated pathology in HIV patients.

Published
2015

25. CD8

Author

E V, Saidakova, K V, Shmagel, L B, Korolevskaya, N G, Shmagel, and V A, Chereshnev

Subjects
Adult, Inflammation, Male, Coinfection, Humans, Female, HIV Infections, CD8-Positive T-Lymphocytes, Middle Aged, Hepatitis C
Abstract

High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients is associated with increased peripheral CD8

Published
2016

26. The size and composition of circulating immune complexes during HIV infection

Author

K. V. Shmagel, N. G. Shmagel, L. B. Korolevskaya, and V. A. Chereshnev

Subjects
biology, business.industry, Biophysics, Human immunodeficiency virus (HIV), HIV Infections, General Chemistry, General Medicine, Composition (combinatorics), Antibodies, Viral, medicine.disease_cause, Biochemistry, Virology, Immune system, Immunoglobulin M, Immunology, medicine, biology.protein, Humans, business
Published
2014

27. Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection

Author

Donald D. Anthony, Janet Robinson, Leonid Margolis, Michael M. Lederman, N. G. Shmagel, Evgeniya V. Saidakova, Valery A. Chereshnev, Daniel C. Douek, K. V. Shmagel, Jean-Charles Grivel, and Larisa B. Korolevskaya

Subjects
0301 basic medicine, Adult, Male, Hepatitis C virus, Inflammation, HIV Infections, medicine.disease_cause, Systemic inflammation, Article, Proinflammatory cytokine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interferon, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, business.industry, Coinfection, Health Policy, virus diseases, Neopterin, Hepatitis C, Hepatitis C, Chronic, medicine.disease, 030104 developmental biology, Infectious Diseases, chemistry, Liver, Immunology, Cytokines, Female, medicine.symptom, business, Biomarkers, medicine.drug
Abstract

Objectives Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods Seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV-1 RNA copies/mL) were included in the study. Two patient groups, HCV-positive/HIV-positive and HCV-negative/HIV-positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)-6, interferon gamma-induced protein (IP)-10, soluble tumour necrosis factor receptor-I (sTNF-RI) and sTNF-RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide (LPS)] and coagulation (d-dimers) were analysed. CD4 naive T cells and CD4 recent thymic emigrants (RTEs) were enumerated. Results Plasma levels of IP-10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I-FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naive T-cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naive T cells and RTEs also merits further exploration.

Published
2015

28. T cell apoptosis in HIV-infected patients with incomplete immune recovery after antiretroviral therapy

Author

V. A. Chereshnev, L. B. Korolevskaya, K. V. Shmagel, E. V. Saidakova, and N. G. Shmagel

Subjects
Adult, Male, Immune recovery, Anti-HIV Agents, T-Lymphocytes, T cell, Apoptosis, HIV Infections, General Biochemistry, Genetics and Molecular Biology, Acquired immunodeficiency syndrome (AIDS), Informed consent, Antiretroviral Therapy, Highly Active, medicine, Humans, Hiv infected patients, T-cell apoptosis, General Immunology and Microbiology, business.industry, General Medicine, medicine.disease, Virology, Antiretroviral therapy, CD4 Lymphocyte Count, medicine.anatomical_structure, Immunology, Female, General Agricultural and Biological Sciences, business, Viral load
Abstract

T cell recovery when replication of the HIV is suppressed is stillnot clear.MATERIALS AND METHODSAn approval of the Ethics Committee of RegionalCenter for AIDS and Infectious Diseases was obtainedfor the study. The written informed consent wasobtained from each patient.Seventynine HIVinfected patients receivingHAART with marked decrease in viral load(

Published
2013

29. The role of interleukin 7 and its cell receptor in a poor recovery of CD4(+) T cells in HIV-infected patients receiving antiretroviral therapy

Author

N. G. Shmagel, L. B. Korolevskaya, K. V. Shmagel, V. A. Chereshnev, and E. V. Saidakova

Subjects
Adult, CD4-Positive T-Lymphocytes, Receptors, Interleukin-7, General Immunology and Microbiology, business.industry, Interleukin-7, Interleukin, HIV Infections, General Medicine, Antiretroviral therapy, General Biochemistry, Genetics and Molecular Biology, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Case-Control Studies, Immunology, Medicine, Hiv infected patients, Humans, General Agricultural and Biological Sciences, business, Receptor
Published
2014

30. [Reactogenicity, safety, immunogenicity and prophylactic effectiveness of polysaccharide pneumococcus vaccine during immunization of HIV-infected patients]

Author

I V, Fel'dblium, V V, Nikolenko, N N, Vorob'eva, É S, Ivanova, N G, Shmagel', K M, Khafizov, G A, Iurganova, and S Ia, Zverev

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Coinfection, Vaccination, HIV Infections, Immunoglobulin E, Middle Aged, Viral Load, Antibodies, Bacterial, Pneumococcal Infections, CD4 Lymphocyte Count, Pneumococcal Vaccines, Streptococcus pneumoniae, Immunoglobulin G, Humans, Female
Abstract

Study safety, reactogenicity, immunogenicity and prophylactic effectiveness of polysaccharide pneumococcus vaccines during immunization of adult HIV-infected patients.200 HIV-infected patients at stages 3 to 4A of the disease aged 20 to 50 years with the quantity of CD4+ T-lymphocytes in blood of no less than 500 microl(-1) took part in the study. 100 individuals immunized with polysaccharide 23-valent pneumococcus vaccine (Pneumo 23, Sanofi Pasteur, France) constituted the observation group. 100 individuals not immunized against pneumococcus infection constituted the comparison group. The groups were standardized by sex, age and disease stage. Vaccine reactogenicity was evaluated by detection of general and local postvaccination reactions, degree of their intensity and duration. Vaccine safety was evaluated based on comparative evaluation of results of general clinical and biochemical studies of blood, general urine analysis, determination of IgE in blood sera, CD4+ T-lymphocytes level, quantity of HIV RNA (viral load) before vaccination and 28 days after the immunization. Vaccine immunogenicity was evaluated by determination in blood sera of IgG against a mixture of Streptococcus pneumoniae polysaccharides comprising Pneumo 23. Prophylaxis effectiveness of the preparation was evaluated by juxtaposition of acute respiratory illness morbidity in observation and control groups.During immunization of HIV-infected patients against pneumococcus infection postvaccination complications, severe local and general postvaccination reactions were not detected, laboratory studies carried out before and after the immunization gave evidence on the lack of progression of the main disease and activization of the infectious process. After the immunization the geometric mean antibody titer against S. pneumoniae increased by 2 times and reached protective level. Index of prophylactic effectiveness of Pneumo 23 vaccines during immunization of HIV-positive patients was 5.6, and relative risk of the disease in the immunized group--0.07, in the control group--0.42.The data provided give evidence on the high prophylactic effect of vaccination of immune compromised HIV-positive patients with a lack of deterioration of the main disease course.

Published
2013

31. [Nikavir in chemoprevention regimens for vertical HIV infection transmission]

Author

E S, Ivanova, N G, Shmagel', and N N, Vorob'eva

Subjects
Adult, Adolescent, Anti-HIV Agents, Lamivudine, Pregnancy, Antiretroviral Therapy, Highly Active, HIV-1, Humans, Female, HIV Infections, Nevirapine, Pregnancy Complications, Infectious, Infectious Disease Transmission, Vertical
Abstract

In 2007-2008, the Perm Territorial Center for Prevention and Control of AIDS and Communicable Diseases investigated the efficacy of the Russian antiretrovirus drug Nikavir used in various chemoprevention (CP) regimens for perinatal HIV infection, by analyzing epidemiological findings and the results of the clinical and laboratory studies of patients. The study covered 38 HIV-infected pregnant women aged 18-32 years and their 38 born babies. From 23-32 weeks gestation to labor, the women started receiving CP using Nikavir in combination with epivir (Group 1; n = 20) and highly active antiretrovirus therapy, including Nikavir with epivir and viramune or kaletra (Group 2; n = 18). During the investigation, the viral burden (VB) and the count of CD4+ lymphocytes were determined and physical examinations were conducted to reveal therapy-induced adverse reactions. Polymerase chain reaction used to test HIV DNA in babies at 1.5 and months of life for early diagnosis of HIV infection. Both CP regimens showed a high efficiency, as suggested by no perinatal infection in the born babies, by a reduction of VB in the HIV-infected women to the undetectable level, and by an increase in the count of CD4+ lymphocytes. No adverse reactions due to the intake of the drugs were recorded.

Published
2010

32. SYSTEMIC INFLAMMATION AND COMPROMISED INTESTINAL BARRIER DURING SUCCESSFUL TREATMENT OF HIV INFECTION

Author

E. V. Saidakova, V. A. Chereshnev, L. B. Korolevskaya, N. G. Shmagel, and K. V. Shmagel

Subjects
0301 basic medicine, business.industry, CD14, Neopterin, Interleukin, Inflammation, General Medicine, Systemic inflammation, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Intestinal mucosa, chemistry, Immunology, medicine, Macrophage, 030212 general & internal medicine, medicine.symptom, business, CD8
Abstract

The relationship between immunity disorders, destruction of intestinal barrier, and development of systemic inflammation during antiviral therapy in patients with HIV infection is a topical issue in terms of suppression of virus replication and reduction of its role in the pathological process. Study object. Blood of HIV-infected patients given antiretroviral therapy (n=21) and non-infected volunteers (n=20). Methods. Identification of cells among CD4+ and CD8+ T-lymphocytes expressing markers of activation (CD38, HLA-DR), depletion (PD-1), and interleukin (IL) 7 receptor (CD127); measurement of blood levels of IL-6, neopterin, soluble CD14 (sCD14), intestinal fatty acid-binding peptide (I-FABP), and bacterial lipopolysaccharide. Correlation analysis of the dependence between cell immunity and systemic inflammation was performed. Results. HIV-infected patients had more activated CD4+ and CD8+ T-lymphocytes and CD4+ T-cells expressing PD-1 marker than non-infected subjects but less CD4+ and CD8+ T-lymphocytes expressing CD127. Blood IL-6, neopterin, soluble CD14, I-FABP, and bacterial lipopolysaccharide levels in the former were higher than in the latter. HIV-infected patients showed significant correlation of cell immunity parameters with blood neopterin and FABP levels. Conclusion. The process of activation, depletion, and regeneration of T-lymphocytes in HIV infection are related to the destruction of intestinal barrier and systemic macrophage activation.

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