aidsВИЧ-инфекция и иммуносупрессииHIV Infection and Immunosuppressive Disorders2077-9828Baltic Medical Education Center10.22328/2077-9828-2023-15-2-7-18aids-806Research ArticleАНАЛИТИЧЕСКИЕ ОБЗОРЫANALYTICAL REVIEWSИммунологическая неэффективность антиретровирусной терапии у ВИЧ-инфицированных пациентовImmunological inefficiency of art in HIV-infected patientshttps://orcid.org/0000-0003-0973-9701БалыкчиноваТ. В.BalykchinovaT. V.

Балыкчинова Татьяна Владимировна — врач-инфекционист

620102, Екатеринбург, ул. Ясная, д. 46

Ekaterinburg

spilnik.tatyana@yandex.ruhttps://orcid.org/0009-0007-8541-1616ЖуковВ. В.ZhukovV. V.

Жуков Вячеслав Владимирович — кандидат медицинских наук, и.о. заместителя главного врача по лечебной части; ассистент кафедры инфекционных болезней и клинической иммунологии

620102, Екатеринбург, ул. Ясная, д. 46;

620028, Екатеринбург, ул. Репина, д. 3

Ekaterinburg

f61@livehiv.ruhttps://orcid.org/0000-0002-8516-018XВолковаС. Б.VolkovaS. В.

Волкова Светлана Борисовна — заведующая клинико-диагностическим отделением № 3

620102, Екатеринбург, ул. Ясная, д. 46

Ekaterinburg

svetlana@olvo.ruhttps://orcid.org/0009-0006-4387-4922РямоваЕ. П.RyamovaE. P.

Рямова Елена Павловна — кандидат медицинских наук, заведующая клинико-диагностическим отделением № 1

620102, Екатеринбург, ул. Ясная, д. 46

Ekaterinburg

spid-kdo1@mis66.ruСвердловский областной центр профилактики и борьбы со СПИДРоссияSverdlovsk Regional Center for the Prevention and Control of AIDSRussian FederationСвердловский областной центр профилактики и борьбы со СПИД; Уральский государственный медицинский университетРоссияSverdlovsk Regional Center for the Prevention and Control of AIDS; Ural State Medical UniversityRussian Federation202320072023152718Copyright © Балыкчинова Т.В., Жуков В.В., Волкова С.Б., Рямова Е.П., 20232023Балыкчинова Т.В., Жуков В.В., Волкова С.Б., Рямова Е.П.Balykchinova T.V., Zhukov V.V., Volkova S.В., Ryamova E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://hiv.bmoc-spb.ru/jour/article/view/806

Широкое внедрение и раннее назначение антиретровирусной терапии существенно улучшает прогноз у людей, живущих с ВИЧ (ЛЖВ),— с увеличением числа CD4+ T-лимфоцитов снижается частота развития вторичных заболеваний и уровень смертности.

У некоторых пациентов на АРТ не удается в полной степени восстановить иммунный статус, несмотря на подавление репликации ВИЧ. Известно, что данные пациенты имеют повышенные риски развития СПИД-ассоциированных болезней и заболеваний, не связанных с ВИЧ. В настоящее время не существует четких критериев для определения случая иммунологической неэффективности АРТ у пациента. Причины формирования недостаточного иммунного ответа изучены недостаточно. Представленный обзор направлен на привлечение внимания специалистов к этой проблеме — обобщены результаты последних исследований и современные данные литературы, описаны возможные механизмы и факторы риска развития иммунологической неэффективности АРТ; представлены исследуемые терапевтические стратегии, направленные на восстановление иммунного статуса у ВИЧ-инфицированных пациентов.

Widespread introduction and early initiation of antiretroviral therapy significantly improves the prognosis in people living with HIV — with an increase in the number of CD4+ T-lymphocytes, the incidence of HIV-related diseases and the mortality rate decreases. Despite suppression of HIV replication, a fraction of ART-treated patients fails to achieve normalization of CD4+ T-cell counts. These patients have an increased risk of clinical progression to AIDS and non-AIDS events. Currently, there are no clear criteria for determining the case of immunological inefficiency of ART. To date, mechanisms of incomplete immune reconstitution in HIV-infected patients have not been fully elucidated. Therefore, in this review, we aim to attract the attention of specialists to this problem — we summarized the results of recent studies and current literature data, described possible mechanisms and risk factors for the development of immunological inefficiency of ART; presented the studied therapeutic strategies aimed at recovering the immunity in HIV-infected patients.

ВИЧ-инфекцияантиретровирусная терапия (АРТ)иммунологическая неэффективностьдискордантный иммунный ответтяжелый иммунодефицитHIV infectionantiretroviral therapy (ART)immunological inefficiency ARTdiscordant immune responsesevere immunodeficiencyReferencesPilcher C., Ospina-Norvell C., Dasgupta A. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting // J. Acquir. Immune Defic. Syndr. 2017. Vol. 74, No. 1. Р. 44–51. doi: https://doi.org/10.1097/QAI.0000000000001134.Pilcher C., Ospina-Norvell C., Dasgupta A. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting // J. Acquir. Immune Defic. Syndr. 2017. Vol. 74, No. 1. Р. 44–51. doi: https://doi.org/10.1097/QAI.0000000000001134.Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Washington, DC: Department of Health and Human Services, 2021. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/poor-cd4-cell-recovery-and-persistent?view=full.Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Washington, DC: Department of Health and Human Services, 2021. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/poor-cd4-cell-recovery-and-persistent?view=full.Rb-Silva R., Goios A., Kelly C. et al. Definition of immunological nonresponse to antiretroviral therapy: a systematic review // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2019. Vol. 82, No. 5. Р. 452–461. doi: https://doi.org/10.1097/QAI.0000000000002157.Rb-Silva R., Goios A., Kelly C. et al. Definition of immunological nonresponse to antiretroviral therapy: a systematic review // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2019. Vol. 82, No. 5. Р. 452–461. doi: https://doi.org/10.1097/QAI.0000000000002157.Yang X., Su B., Zhang X. et al. Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders // Journal of leukocyte biology. 2020. Vol. 107, No. 4. Р. 597–612. doi: https://doi.org/10.1002/JLB.4MR1019-189R.Yang X., Su B., Zhang X. et al. Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders // Journal of leukocyte biology. 2020. Vol. 107, No. 4. Р. 597–612. doi: https://doi.org/10.1002/JLB.4MR1019-189R.Шмагель К.В. Дискордантный ответ CD4+ T-лимфоцитов на антиретровирусную терапию // ВИЧ-инфекция и иммуносупрессии. 2019. Т. 11, № 1. doi: https://doi.org/10.22328/2077-9828-2019-11-1.Shmagel K.V. Discordant response of CD4+ T-lymphocytes to antiretroviral therapy. HIV infection and immunosuppression, 2019, Vol. 11, No. 1 (In Russ.) doi: https://doi.org/10.22328/2077-9828-2019-11-1.Kelly C., Gaskell K.M., Richardson M. et al. Discordant immune response with antiretroviral therapy in HIV-1: a systematic review of clinical outcomes // PloS Оne. 2016. Vol. 11, No. 6. Р. e0156099. doi: https://doi.org/10.1371/journal.pone.0156099.Kelly C., Gaskell K.M., Richardson M. et al. Discordant immune response with antiretroviral therapy in HIV-1: a systematic review of clinical outcomes // PloS Оne. 2016. Vol. 11, No. 6. Р. e0156099. doi: https://doi.org/10.1371/journal.pone.0156099.Олейник А.Ф., Фазылов В.Х. Причины иммунологической неэффективности антиретровирусной терапии у пациентов с ВИЧ-инфекцией // Казанский медицинский журнал. 2014. Т. 95, № 4.Oleinik A.F., Fazylov V.H. Causes of immunological inefficiency of antiretroviral therapy in patients with HIV infection. Kazan Medical Journal, 2014, Vol. 95. No. 4 (In Russ.).Tan R., Westfall A.O., Willig J.H. et al. Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2008. Vol. 47, No. 5. Р. 553–558. doi: https://doi.org/10.1097/qai.0b013e31816856c5.Tan R., Westfall A.O., Willig J.H. et al. Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2008. Vol. 47, No. 5. Р. 553–558. doi: https://doi.org/10.1097/qai.0b013e31816856c5.Zoufaly A., Cozzi-Lepri A., Reekie J. et al. Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe // PloS Оne. 2014. Vol. 9, No. 1. Р. e87160. doi: https://doi.org/10.1371/journal.pone.0087160.Zoufaly A., Cozzi-Lepri A., Reekie J. et al. Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe // PloS Оne. 2014. Vol. 9, No. 1. Р. e87160. doi: https://doi.org/10.1371/journal.pone.0087160.Lapadula G., Cozzi-Lepri A., Marchetti G. et al. Risk of clinical progression among patients with immunological nonresponse despite virological suppression after combination antiretroviral treatment // AIDS. 2013. Vol. 27, No. 5. Р. 769–779. doi: https://doi.org/10.1097/QAD.0b013e32835cb747.Lapadula G., Cozzi-Lepri A., Marchetti G. et al. Risk of clinical progression among patients with immunological nonresponse despite virological suppression after combination antiretroviral treatment // AIDS. 2013. Vol. 27, No. 5. Р. 769–779. doi: https://doi.org/10.1097/QAD.0b013e32835cb747.Клинические рекомендации Министерства здравоохранения Российской Федерации. ВИЧ-инфекция у взрослых, 2020 год. http://rushiv.ru/klinicheskie-rekomendatsii-vich-infektsiya-u-vzroslyh-2020/Clinical recommendations of the Ministry of Health of the Russian Federation. HIV infection in adults, 2020 (In Russ.). http://rushiv.ru/klinicheskie-rekomendatsii-vich-infektsiya-u-vzroslyh-2020/ВИЧ-инфекция и СПИД: национальное руководство / под ред. В.В.Покровского. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2020. 696 с.: ил. (Серия «Национальные руководства»). doi: https://doi.org/10.33029/9704-5421-3-2020-VIC-1-696HIV infection and AIDS: a national guide / edited by V.V.Pokrovsky. 2 nd ed., reprint. and add. Moscow: GEOTAR-Media, 2020. 696 p.: ill. (Series «National Guides») (In Russ.). doi: https://doi.org/10.33029/9704-5421-3-2020-VIC-1-696Lu W., Mehraj V., Vyboh K. et al. CD4: CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients // Journal of the International AIDS Society. 2015. Vol. 18, No. 1. Р. 20052. doi: https://doi.org/10.7448/IAS.18.1.20052.Lu W., Mehraj V., Vyboh K. et al. CD4: CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients // Journal of the International AIDS Society. 2015. Vol. 18, No. 1. Р. 20052. doi: https://doi.org/10.7448/IAS.18.1.20052.Kaufmann G.R., Furrer H., Ledergerber B. et al. Characteristics, Determinants, and clinical relevance of CD4 T cell recovery to <500 cells/μL in HIV type 1-infected individuals receiving potent antiretroviral therapy // Clinical infectious diseases. 2005. Vol. 41, No. 3. Р. 361–372. doi: https://doi.org/10.1086/431484Kaufmann G.R., Furrer H., Ledergerber B. et al. Characteristics, Determinants, and clinical relevance of CD4 T cell recovery to <500 cells/μL in HIV type 1-infected individuals receiving potent antiretroviral therapy // Clinical infectious diseases. 2005. Vol. 41, No. 3. Р. 361–372. doi: https://doi.org/10.1086/431484Jarrin I., Pantazis N., Dalmau J. et al. Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4+ T-cell recovery once HIV-1 suppression is achieved? // AIDS (London, England). 2015. Vol. 29, No. 17. Р. 2323. doi: https://doi.org/10.1097/QAD.0000000000000805.Jarrin I., Pantazis N., Dalmau J. et al. Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4+ T-cell recovery once HIV-1 suppression is achieved? // AIDS (London, England). 2015. Vol. 29, No. 17. Р. 2323. doi: https://doi.org/10.1097/QAD.0000000000000805.Engsig F.N., Gerstoft J., Kronborg G. et al. Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study // BMC infectious diseases. 2010. Vol. 10, No. 1. Р. 1–9. doi: https://doi.org/10.1186/1471-2334-10-318.Engsig F.N., Gerstoft J., Kronborg G. et al. Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study // BMC infectious diseases. 2010. Vol. 10, No. 1. Р. 1–9. doi: https://doi.org/10.1186/1471-2334-10-318.Tincati C., Merlini E., Braidotti P. et al. Impaired gut junctional complexes feature late-treated individuals with suboptimal CD4+ T-cell recovery upon virologically suppressive combination antiretroviral therapy // AIDS. 2016. Vol. 30, No. 7. Р. 991–1003. doi: https://doi.org/10.1097/QAD.0000000000001015.Tincati C., Merlini E., Braidotti P. et al. Impaired gut junctional complexes feature late-treated individuals with suboptimal CD4+ T-cell recovery upon virologically suppressive combination antiretroviral therapy // AIDS. 2016. Vol. 30, No. 7. Р. 991–1003. doi: https://doi.org/10.1097/QAD.0000000000001015.Younes S.A., Talla A., Ribeiro S.P. et al. Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction // The Journal of clinical investigation. 2018. Vol. 128, No. 11. Р. 5083–5094. doi: https://doi.org/10.1172/JCI120245.Younes S.A., Talla A., Ribeiro S.P. et al. Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction // The Journal of clinical investigation. 2018. Vol. 128, No. 11. Р. 5083–5094. doi: https://doi.org/10.1172/JCI120245.Zhang L.X., Song J.W., Zhang C. et al. Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment // Clinical immunology. 2021. Vol. 229. Р. 108773. doi: https://doi.org/10.1016/j.clim.2021.108773.Zhang L.X., Song J.W., Zhang C. et al. Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment // Clinical immunology. 2021. Vol. 229. Р. 108773. doi: https://doi.org/10.1016/j.clim.2021.108773.Rodríguez-Gallego E., Gómez J., Pacheco Y.M. et al. A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients // AIDS (London, England). 2018. Vol. 32, No. 5. Р. 565. doi: https://doi.org/10.1097/QAD.0000000000001730Rodríguez-Gallego E., Gómez J., Pacheco Y.M. et al. A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients // AIDS (London, England). 2018. Vol. 32, No. 5. Р. 565. doi: https://doi.org/10.1097/QAD.0000000000001730Rosado-Sánchez I., Herrero-Fernández I., Álvarez-Ríos A.I. et al. A lower baseline CD4/CD8 T-cell ratio is independently associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects // Antimicrobial agents and chemotherapy. 2017. Vol. 61, No. 8. Р. e00605–17. doi: https://doi.org/10.1128/AAC.00605-17.Rosado-Sánchez I., Herrero-Fernández I., Álvarez-Ríos A.I. et al. A lower baseline CD4/CD8 T-cell ratio is independently associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects // Antimicrobial agents and chemotherapy. 2017. Vol. 61, No. 8. Р. e00605–17. doi: https://doi.org/10.1128/AAC.00605-17.Cenderello G., De Maria A. Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: clinical evaluation, classification, management prospects // Expert Review of Anti-infective Therapy. 2016. Vol. 14, No. 1. Р. 29–40. doi: https://doi.org/10.1586/14787210.2016.1106937.Cenderello G., De Maria A. Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: clinical evaluation, classification, management prospects // Expert Review of Anti-infective Therapy. 2016. Vol. 14, No. 1. Р. 29–40. doi: https://doi.org/10.1586/14787210.2016.1106937.Resino S., Navarrete-Muñoz M.A., Blanco J. et al. IL7RA rs6897932 polymorphism is associated with better CD4+ T-cell recovery in HIV infected patients starting combination antiretroviral therapy // Biomolecules. 2019. Vol. 9, No. 6. Р. 233. doi: https://doi.org/10.3390/biom9060233.Resino S., Navarrete-Muñoz M.A., Blanco J. et al. IL7RA rs6897932 polymorphism is associated with better CD4+ T-cell recovery in HIV infected patients starting combination antiretroviral therapy // Biomolecules. 2019. Vol. 9, No. 6. Р. 233. doi: https://doi.org/10.3390/biom9060233.Yong Y.K., Shankar E.M., Westhorpe C.L. et al. Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy // AIDS. 2016. Vol. 30, No. 14. Р. 2159–2168. doi: https://doi.org/10.1097/QAD.0000000000001179.Yong Y.K., Shankar E.M., Westhorpe C.L. et al. Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy // AIDS. 2016. Vol. 30, No. 14. Р. 2159–2168. doi: https://doi.org/10.1097/QAD.0000000000001179.Rb-Silva R., Nobrega C., Azevedo C. et al. Thymic function as a predictor of immune recovery in chronically HIV-infected patients initiating antiretroviral therapy // Frontiers in immunology. 2019. Vol. 10. Р. 25. doi: https://doi.org/10.3389/fimmu.2019.00025.Rb-Silva R., Nobrega C., Azevedo C. et al. Thymic function as a predictor of immune recovery in chronically HIV-infected patients initiating antiretroviral therapy // Frontiers in immunology. 2019. Vol. 10. Р. 25. doi: https://doi.org/10.3389/fimmu.2019.00025.Rosado-Sánchez I., Herrero-Fernández I., Genebat M. et al. Thymic function impacts the peripheral CD4/CD8 ratio of HIV-infected subjects // Clinical Infectious Diseases. 2017. Vol. 64, No. 2. Р. 152–158. doi: https://doi.org/10.1093/cid/ciw711.Rosado-Sánchez I., Herrero-Fernández I., Genebat M. et al. Thymic function impacts the peripheral CD4/CD8 ratio of HIV-infected subjects // Clinical Infectious Diseases. 2017. Vol. 64, No. 2. Р. 152–158. doi: https://doi.org/10.1093/cid/ciw711.Estes J.D. Pathobiology of HIV/SIV-associated changes in secondary lymphoid tissues // Immunological reviews. 2013. Vol. 254, No. 1. Р. 65–77. doi: https://doi.org/10.1111/imr.12070.Estes J.D. Pathobiology of HIV/SIV-associated changes in secondary lymphoid tissues // Immunological reviews. 2013. Vol. 254, No. 1. Р. 65–77. doi: https://doi.org/10.1111/imr.12070.Zeng M., Southern P.J., Reilly C.S. Lymphoid tissue damage in HIV-1 infection depletes naive T cells and limits T cell reconstitution after antiretroviral therapy // PLoS Pathog. 2012. Vol. 8, No. 1. e1002437. doi: https://doi.org/10.1371/journal.ppat.1002437.Zeng M., Southern P.J., Reilly C.S. Lymphoid tissue damage in HIV-1 infection depletes naive T cells and limits T cell reconstitution after antiretroviral therapy // PLoS Pathog. 2012. Vol. 8, No. 1. e1002437. doi: https://doi.org/10.1371/journal.ppat.1002437.Diaz A., Alós L., León A. et al. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients // AIDS. 2010. Vol. 24, No. 13. Р. 2029–2039. doi: https://doi.org/10.1097/QAD.0b013e32833c3268.Diaz A., Alós L., León A. et al. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients // AIDS. 2010. Vol. 24, No. 13. Р. 2029–2039. doi: https://doi.org/10.1097/QAD.0b013e32833c3268.Шмагель К.В., Шмагель Н.Г., Черешнев В.А. Активация иммунитета при ВИЧ-инфекции // Медицинская иммунология. 2017. Т. 19, № 5. С. 489–504.Shmagel K.V., Shmagel N.G., Chereshnev V.A. Activation of immunity in HIV infection. Medical immunology, 2017, Vol. 19, No. 5, pp. 489–504 (In Russ.).Massanella M., Negredo E., Pérez-Álvarez N. et al. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART // AIDS. 2010. Vol. 24, No. 7. Р. 959–968. doi: https://doi.org/10.1097/QAD.0b013e328337b957.Massanella M., Negredo E., Pérez-Álvarez N. et al. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART // AIDS. 2010. Vol. 24, No. 7. Р. 959–968. doi: https://doi.org/10.1097/QAD.0b013e328337b957.Massanella M., Gómez-Mora E., Carrillo J. et al. Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery // Journal of translational medicine. 2015. Vol. 13, No. 1. Р. 1–11. doi: https://doi.org/10.1186/s12967-015-0601-2.Massanella M., Gómez-Mora E., Carrillo J. et al. Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery // Journal of translational medicine. 2015. Vol. 13, No. 1. Р. 1–11. doi: https://doi.org/10.1186/s12967-015-0601-2.Бобкова М. Латентность ВИЧ. М.: Человек, 2021. 228 с.: ил.Bobkova M. HIV latency. Moscow: Рublishing house Man, 2021. 228 p., ill. (In Russ.).Xie Y., Sun J., Wei L. et al. Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals // BMC microbiology. 2021. Vol. 21, Nо. 1. Р. 1–12. doi: https://doi.org/10.1186/s12866-020-02074-1.Xie Y., Sun J., Wei L. et al. Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals // BMC microbiology. 2021. Vol. 21, Nо. 1. Р. 1–12. doi: https://doi.org/10.1186/s12866-020-02074-1.Lu W., Feng Y., Jing F. et al. Association between gut microbiota and CD4 recovery in HIV-1 infected patients // Frontiers in microbiology. 2018. Vol. 9. Р. 1451. doi: https://doi.org/10.3389/fmicb.2018.01451Lu W., Feng Y., Jing F. et al. Association between gut microbiota and CD4 recovery in HIV-1 infected patients // Frontiers in microbiology. 2018. Vol. 9. Р. 1451. doi: https://doi.org/10.3389/fmicb.2018.01451Ahn M.Y., Jiamsakul A., Khusuwan S. et al. The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV // Journal of the International AIDS Society. 2019. Vol. 22, No. 2. Р. e25228. doi: https://doi.org/10.1002/jia2.25228.Ahn M.Y., Jiamsakul A., Khusuwan S. et al. The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV // Journal of the International AIDS Society. 2019. Vol. 22, No. 2. Р. e25228. doi: https://doi.org/10.1002/jia2.25228.Boatman J.A., Baker J.V., Emery S. et al. Risk factors for low CD4+ count recovery despite viral suppression among participants initiating antiretroviral treatment with CD4+ Counts> 500 cells/mm3: findings from the strategic timing of antiretroviral treatment (START) trial // Journal of acquired immune deficiency syndromes (1999). 2019. Vol. 81, No. 1. Р. 10. doi: https://doi.org/10.1097/QAI.0000000000001967.Boatman J.A., Baker J.V., Emery S. et al. Risk factors for low CD4+ count recovery despite viral suppression among participants initiating antiretroviral treatment with CD4+ Counts> 500 cells/mm3: findings from the strategic timing of antiretroviral treatment (START) trial // Journal of acquired immune deficiency syndromes (1999). 2019. Vol. 81, No. 1. Р. 10. doi: https://doi.org/10.1097/QAI.0000000000001967.Hoffmann C., Rockstroh J.K., HIV 2014/2015. Hamburg: Medizin Focus Verlag, 2015. Р. 906.Hoffmann C., Rockstroh J.K., HIV 2014/2015. Hamburg: Medizin Focus Verlag, 2015. Р. 906.Ignacio R.B., Ddungu H., Uldrick T.S. Untangling the Effects of Chemotherapy and HIV on CD4 Counts — Implications for Immunotherapy in HIV and Cancer // JAMA oncology. 2020. Vol. 6, No. 2. Р. 235–236. doi: https://doi.org/10.1001/jamaoncol.2019.4634.Ignacio R.B., Ddungu H., Uldrick T.S. Untangling the Effects of Chemotherapy and HIV on CD4 Counts — Implications for Immunotherapy in HIV and Cancer // JAMA oncology. 2020. Vol. 6, No. 2. Р. 235–236. doi: https://doi.org/10.1001/jamaoncol.2019.4634.Calkins K.L., Chander G., Joshu C.E. et al. Immune status and associated mortality after cancer treatment among individuals with HIV in the antiretroviral therapy era // JAMA oncology. 2020. Vol. 6, No. 2. Р. 227–235. doi: https://doi.org/10.1001/jamaoncol.2019.4648.Calkins K.L., Chander G., Joshu C.E. et al. Immune status and associated mortality after cancer treatment among individuals with HIV in the antiretroviral therapy era // JAMA oncology. 2020. Vol. 6, No. 2. Р. 227–235. doi: https://doi.org/10.1001/jamaoncol.2019.4648.Attallah M.A., Jara M.D.J., Gautam A.S. et al. A review of the use of biological agents in human immunodeficiency virus positive patients with rheumatological diseases // Cureus. 2020. Vol. 12, No. 10. doi: https://doi.org/10.7759/cureus.10970.Attallah M.A., Jara M.D.J., Gautam A.S. et al. A review of the use of biological agents in human immunodeficiency virus positive patients with rheumatological diseases // Cureus. 2020. Vol. 12, No. 10. doi: https://doi.org/10.7759/cureus.10970.Dussauze H., Bourgault I., Doleris L.M. et al. Systemic corticosteroid treatment and risk of infectious diseases // La Revue de Médecine Interne. 2007. Vol. 28, No. 12. Р. 841–851. doi: https://doi.org/10.1016/j.revmed.2007.05.030.Dussauze H., Bourgault I., Doleris L.M. et al. Systemic corticosteroid treatment and risk of infectious diseases // La Revue de Médecine Interne. 2007. Vol. 28, No. 12. Р. 841–851. doi: https://doi.org/10.1016/j.revmed.2007.05.030.So-Armah K., Benjamin L.A., Bloomfield G.S. et al. HIV and cardiovascular disease // The lancet HIV. 2020. Vol. 7, No. 4. Р. e279-e293. doi: https://doi.org/10.1016/S2352-3018(20)30036-9.So-Armah K., Benjamin L.A., Bloomfield G.S. et al. HIV and cardiovascular disease // The lancet HIV. 2020. Vol. 7, No. 4. Р. e279-e293. doi: https://doi.org/10.1016/S2352-3018(20)30036-9.Brown T.T., Tassiopoulos K., Bosch R.J. et al. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy // Diabetes care. 2010. Vol. 33, No. 10. Р. 2244–2249. doi: https://doi.org/10.2337/dc10-0633.Brown T.T., Tassiopoulos K., Bosch R.J. et al. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy // Diabetes care. 2010. Vol. 33, No. 10. Р. 2244–2249. doi: https://doi.org/10.2337/dc10-0633.Virot E., Duclos A., Adelaide L. et al. Autoimmune diseases and HIV infection: a cross-sectional study // Medicine. 2017. Vol. 96, No. 4. doi: https://doi.org/10.1097/MD.0000000000005769.Virot E., Duclos A., Adelaide L. et al. Autoimmune diseases and HIV infection: a cross-sectional study // Medicine. 2017. Vol. 96, No. 4. doi: https://doi.org/10.1097/MD.0000000000005769.Marcus J.L., Leyden W.A., Chao C.R. et al. Differences in response to antiretroviral therapy by sex and hepatitis C infection status // AIDS patient care and STDs. 2015. Vol. 29, No. 7. Р. 370–378. doi: https://doi.org/10.1089/apc.2015.0040.Marcus J.L., Leyden W.A., Chao C.R. et al. Differences in response to antiretroviral therapy by sex and hepatitis C infection status // AIDS patient care and STDs. 2015. Vol. 29, No. 7. Р. 370–378. doi: https://doi.org/10.1089/apc.2015.0040.Van Griensven J., Phirum L., Choun K. et al. Hepatitis B and C co-infection among HIV-infected adults while on antiretroviral treatment: long-term survival, CD4 cell count recovery and antiretroviral toxicity in Cambodia // PloS Оne. 2014. Vol. 9, No. 2. Р. e88552. doi: https://doi.org/10.1371/journal.pone.0088552.Van Griensven J., Phirum L., Choun K. et al. Hepatitis B and C co-infection among HIV-infected adults while on antiretroviral treatment: long-term survival, CD4 cell count recovery and antiretroviral toxicity in Cambodia // PloS Оne. 2014. Vol. 9, No. 2. Р. e88552. doi: https://doi.org/10.1371/journal.pone.0088552.Chen M., Wong W.W., Law M.G. et al. Hepatitis B and C co-infection in HIV patients from the TREAT Asia HIV observational database: analysis of risk factors and survival // PLoS One. 2016. Vol. 11, No. 3. e0150512. doi: https://doi.org/10.1371/journal.pone.0150512.Chen M., Wong W.W., Law M.G. et al. Hepatitis B and C co-infection in HIV patients from the TREAT Asia HIV observational database: analysis of risk factors and survival // PLoS One. 2016. Vol. 11, No. 3. e0150512. doi: https://doi.org/10.1371/journal.pone.0150512.Peters L., Mocroft A., Soriano V. et al. Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2009. Vol. 50, No. 5. Р. 457–463. doi: https://doi.org/10.1097/QAI.0b013e318198a0e1.Peters L., Mocroft A., Soriano V. et al. Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression // JAIDS Journal of Acquired Immune Deficiency Syndromes. 2009. Vol. 50, No. 5. Р. 457–463. doi: https://doi.org/10.1097/QAI.0b013e318198a0e1.Nuñez J.A.P., Gonzalez-Garcia J., Berenguer J. et al. Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients // Medicine. 2018. Vol. 97, No. 38. doi: https://doi.org/10.1097/MD.0000000000012238.Nuñez J.A.P., Gonzalez-Garcia J., Berenguer J. et al. Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients // Medicine. 2018. Vol. 97, No. 38. doi: https://doi.org/10.1097/MD.0000000000012238.Wandeler G., Gsponer T., Bihl F. et al. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study // The Journal of infectious diseases. 2013. Vol. 208, No. 9. Р. 1454–1458. doi: https://doi.org/10.1093/infdis/jit351.Wandeler G., Gsponer T., Bihl F. et al. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study // The Journal of infectious diseases. 2013. Vol. 208, No. 9. Р. 1454–1458. doi: https://doi.org/10.1093/infdis/jit351.Chun H.M., Mesner O., Thio C. L. et al. HIV outcomes in Hepatitis B virus coinfected individuals on HAART // Journal of acquired immune deficiency syndromes (1999). 2014. Vol. 66, No. 2. Р. 197. doi: https://doi.org/10.1097/QAI.0000000000000142.Chun H.M., Mesner O., Thio C. L. et al. HIV outcomes in Hepatitis B virus coinfected individuals on HAART // Journal of acquired immune deficiency syndromes (1999). 2014. Vol. 66, No. 2. Р. 197. doi: https://doi.org/10.1097/QAI.0000000000000142.Smeaton L., Saulynas M., Hwang H. et al. Characterization of HIV-HBV co-infection in a multi-national HIV-infected cohort // AIDS (London, England). 2013. Vol. 27, No. 2. Р. 191. doi: https://doi.org/10.1097/QAD.0b013e32835a9984.Smeaton L., Saulynas M., Hwang H. et al. Characterization of HIV-HBV co-infection in a multi-national HIV-infected cohort // AIDS (London, England). 2013. Vol. 27, No. 2. Р. 191. doi: https://doi.org/10.1097/QAD.0b013e32835a9984.Wang H., Li Y., Zhang C. et al. Immunological and virological responses to cART in HIV/HBV co-infected patients from a multicenter cohort // AIDS (London, England). 2012. Vol. 26, No. 14. Р. 1755–1763. doi: https://doi.org/10.1097/qad.0b013e328355ced2.Wang H., Li Y., Zhang C. et al. Immunological and virological responses to cART in HIV/HBV co-infected patients from a multicenter cohort // AIDS (London, England). 2012. Vol. 26, No. 14. Р. 1755–1763. doi: https://doi.org/10.1097/qad.0b013e328355ced2.Gomez-Mora E., Massanella M., Garcia E. et al. Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery // PloS Оne. 2017. Vol. 12, No. 9. Р. e0184433. doi: https://doi.org/10.1371/journal.pone.0184433.Gomez-Mora E., Massanella M., Garcia E. et al. Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery // PloS Оne. 2017. Vol. 12, No. 9. Р. e0184433. doi: https://doi.org/10.1371/journal.pone.0184433.Cingolani A., Cozzi Lepri A., Castagna A. et al. Impaired CD4 T-cell count response to combined antiretroviral therapy in antiretroviral-naive HIV-infected patients presenting with tuberculosis as AIDS-defining condition // Clinical infectious diseases. 2012. Vol. 54, No. 6. Р. 853–861. doi: https://doi.org/10.1097/01.aids.0000434936.57880.cd.Cingolani A., Cozzi Lepri A., Castagna A. et al. Impaired CD4 T-cell count response to combined antiretroviral therapy in antiretroviral-naive HIV-infected patients presenting with tuberculosis as AIDS-defining condition // Clinical infectious diseases. 2012. Vol. 54, No. 6. Р. 853–861. doi: https://doi.org/10.1097/01.aids.0000434936.57880.cd.Skogmar S., Schön T., Balcha T.T. et al. CD4 cell levels during treatment for tuberculosis (TB) in Ethiopian adults and clinical markers associated with CD4 lymphocytopenia // PloS One. 2013. Vol. 8, No. 12. Р. e83270. doi: https://doi.org/10.1371/journal.pone.0083270.Skogmar S., Schön T., Balcha T.T. et al. CD4 cell levels during treatment for tuberculosis (TB) in Ethiopian adults and clinical markers associated with CD4 lymphocytopenia // PloS One. 2013. Vol. 8, No. 12. Р. e83270. doi: https://doi.org/10.1371/journal.pone.0083270.Reepalu A., Balcha T.T., Sturegård E. et al. Long-term outcome of antiretroviral treatment in patients with and without concomitant tuberculosis receiving health center–based care — results from a prospective cohort study // Open forum infectious diseases. US: Oxford University Press, 2017. Vol. 4, No. 4. Р. ofx219. doi: https://doi.org/10.1093/ofid/ofx219.Reepalu A., Balcha T.T., Sturegård E. et al. Long-term outcome of antiretroviral treatment in patients with and without concomitant tuberculosis receiving health center–based care — results from a prospective cohort study // Open forum infectious diseases. US: Oxford University Press, 2017. Vol. 4, No. 4. Р. ofx219. doi: https://doi.org/10.1093/ofid/ofx219.Gupta R.K., Brown A.E., Zenner D. et al. CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection // AIDS. 2015. Vol. 29, No. 11. Р. 1363–1368. doi: https://doi.org/10.1097/QAD.0000000000000685.Gupta R.K., Brown A.E., Zenner D. et al. CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection // AIDS. 2015. Vol. 29, No. 11. Р. 1363–1368. doi: https://doi.org/10.1097/QAD.0000000000000685.Jiang W., Luo Z., Martin L. et al. Drug use is associated with anti-CD4 IgG-mediated CD4+ T cell death and poor CD4+ T cell recovery in viral-suppressive HIV-infected individuals under antiretroviral therapy // Current HIV research. 2018. Vol. 16, No. 2. Р. 143–150. doi: https://doi.org/10.2174/1570162X16666180703151208.Jiang W., Luo Z., Martin L. et al. Drug use is associated with anti-CD4 IgG-mediated CD4+ T cell death and poor CD4+ T cell recovery in viral-suppressive HIV-infected individuals under antiretroviral therapy // Current HIV research. 2018. Vol. 16, No. 2. Р. 143–150. doi: https://doi.org/10.2174/1570162X16666180703151208.Li X., He W., Wen Y. et al. The Impact of Addictive Drugs on HIV Immunopathogenesis // Journal of Drug and Alcohol Research. 2021. Vol. 10, No. 11. Р. 1–8. https://www.ashdin.com/abstract/the-impact-of-addictive-drugs-on-hiv-immunopathogenesis-88397.html.Li X., He W., Wen Y. et al. The Impact of Addictive Drugs on HIV Immunopathogenesis // Journal of Drug and Alcohol Research. 2021. Vol. 10, No. 11. Р. 1–8. https://www.ashdin.com/abstract/the-impact-of-addictive-drugs-on-hiv-immunopathogenesis-88397.html.Banerjee S., Sindberg G., Wang F. et al. Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation // Mucosal immunology. 2016. Vol. 9, No. 6. Р. 1418–1428. doi: https://doi.org/10.1038/mi.2016.9.Banerjee S., Sindberg G., Wang F. et al. Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation // Mucosal immunology. 2016. Vol. 9, No. 6. Р. 1418–1428. doi: https://doi.org/10.1038/mi.2016.9.Koethe J.R., Jenkins C.A., Lau B. et al. Higher time-updated body mass index: association with improved CD4+ cell recovery on HIV treatment // Journal of acquired immune deficiency syndromes (1999). 2016. Vol. 73, No. 2. Р. 197. doi: https://doi.org/10.1097/QAI.0000000000001035.Koethe J.R., Jenkins C.A., Lau B. et al. Higher time-updated body mass index: association with improved CD4+ cell recovery on HIV treatment // Journal of acquired immune deficiency syndromes (1999). 2016. Vol. 73, No. 2. Р. 197. doi: https://doi.org/10.1097/QAI.0000000000001035.Li X., Ding H., Geng W. et al. Predictive effects of body mass index on immune reconstitution among HIV-infected HAART users in China // BMC infectious diseases. 2019. Vol. 19, No. 1. Р. 1–9. doi: https://doi.org/10.1186/s12879-019-3991-6.Li X., Ding H., Geng W. et al. Predictive effects of body mass index on immune reconstitution among HIV-infected HAART users in China // BMC infectious diseases. 2019. Vol. 19, No. 1. Р. 1–9. doi: https://doi.org/10.1186/s12879-019-3991-6.Palmer C.S., Ostrowski M., Gouillou M. et al. Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection // AIDS (London, England). 2014. Vol. 28, No. 3. Р. 297. doi: https://doi.org/10.1097/QAD.0000000000000128Palmer C.S., Ostrowski M., Gouillou M. et al. Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection // AIDS (London, England). 2014. Vol. 28, No. 3. Р. 297. doi: https://doi.org/10.1097/QAD.0000000000000128Kołodziej J. Effects of stress on HIV infection progression // HIV & AIDS Review. 2016. Vol. 15, No. 1. Р. 13–16. doi: https://doi.org/10.1016/j.hivar.2015.07.003.Kołodziej J. Effects of stress on HIV infection progression // HIV & AIDS Review. 2016. Vol. 15, No. 1. Р. 13–16. doi: https://doi.org/10.1016/j.hivar.2015.07.003.Zefferino R., Di Gioia S., Conese M. Molecular links between endocrine, nervous and immune system during chronic stress // Вrain and Behavior. 2021. Vol. 11, No. 2. Р. e01960. doi: https://doi.org/10.1002/brb3.1960.Zefferino R., Di Gioia S., Conese M. Molecular links between endocrine, nervous and immune system during chronic stress // Вrain and Behavior. 2021. Vol. 11, No. 2. Р. e01960. doi: https://doi.org/10.1002/brb3.1960.Patterson S., Moran P., Epel E. et al. Cortisol patterns are associated with T cell activation in HIV // PloS Оne. 2013. Vol. 8, No. 7. Р. e63429. doi: https://doi.org/10.1371/journal.pone.0063429.Patterson S., Moran P., Epel E. et al. Cortisol patterns are associated with T cell activation in HIV // PloS Оne. 2013. Vol. 8, No. 7. Р. e63429. doi: https://doi.org/10.1371/journal.pone.0063429.Zhang F., Sun M., Sun J. et al. The risk factors for suboptimal CD4 recovery in HIV infected population: an observational and retrospective study in Shanghai, China // Bioscience trends. 2015. Vol. 9, No. 5. Р. 335–341. doi: https://doi.org/10.5582/bst.2015.01107.Zhang F., Sun M., Sun J. et al. The risk factors for suboptimal CD4 recovery in HIV infected population: an observational and retrospective study in Shanghai, China // Bioscience trends. 2015. Vol. 9, No. 5. Р. 335–341. doi: https://doi.org/10.5582/bst.2015.01107.Tanuma J., Matsumoto S., Haneuse S. et al. Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam // Journal of the International AIDS Society. 2017. Vol. 20, No. 4. Р. e25030. doi: https://doi.org/10.1002/jia2.25030.Tanuma J., Matsumoto S., Haneuse S. et al. Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam // Journal of the International AIDS Society. 2017. Vol. 20, No. 4. Р. e25030. doi: https://doi.org/10.1002/jia2.25030.Edwards J.K., Hall H.I., Mathews W.C. et al. Virologic suppression and CD4 cell count recovery after initiation of raltegravir-or efavirenz-containing HIV treatment regimens // AIDS (London, England). 2018. Vol. 32, No. 2. Р. 261. doi: https://doi.org/10.1097/QAD.0000000000001668.Edwards J.K., Hall H.I., Mathews W.C. et al. Virologic suppression and CD4 cell count recovery after initiation of raltegravir-or efavirenz-containing HIV treatment regimens // AIDS (London, England). 2018. Vol. 32, No. 2. Р. 261. doi: https://doi.org/10.1097/QAD.0000000000001668.Blanco J.R., Alejos B., Moreno S. Impact of dolutegravir and efavirenz on immune recovery markers: results from a randomized clinical trial // Clinical Microbiology and Infection. 2018. Vol. 24, No. 8. Р. 900–907. doi: https://doi.org/10.1016/j.cmi.2017.11.016.Blanco J.R., Alejos B., Moreno S. Impact of dolutegravir and efavirenz on immune recovery markers: results from a randomized clinical trial // Clinical Microbiology and Infection. 2018. Vol. 24, No. 8. Р. 900–907. doi: https://doi.org/10.1016/j.cmi.2017.11.016.Gatell J.M., Assoumou L., Moyle G. et al. Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk // AIDS (London, England). 2017. Vol. 31, No. 18. Р. 2503. doi: https://doi.org/10.1097/QAD.0000000000001675Gatell J.M., Assoumou L., Moyle G. et al. Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk // AIDS (London, England). 2017. Vol. 31, No. 18. Р. 2503. doi: https://doi.org/10.1097/QAD.0000000000001675Asundi A., Robles Y., Starr T. et al. Immunological and neurometabolite changes associated with switch from efavirenz to an integrase inhibitor // Journal of acquired immune deficiency syndromes (1999). 2019. Vol. 81, No. 5. doi: https://doi.org/10.1097/QAI.0000000000002079.Asundi A., Robles Y., Starr T. et al. Immunological and neurometabolite changes associated with switch from efavirenz to an integrase inhibitor // Journal of acquired immune deficiency syndromes (1999). 2019. Vol. 81, No. 5. doi: https://doi.org/10.1097/QAI.0000000000002079.Rusconi S., Vitiello P., Adorni F. et al. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial // PloS Оne. 2013. Vol. 8, No. 11. Р. e80157. doi: https://doi.org/10.1371/journal.pone.0080157.Rusconi S., Vitiello P., Adorni F. et al. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial // PloS Оne. 2013. Vol. 8, No. 11. Р. e80157. doi: https://doi.org/10.1371/journal.pone.0080157.Massanella M., Negredo E., Puig J. et al. Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery // AIDS. 2012. Vol. 26, No. 18. Р. 2285–2293. doi: https://doi.org/10.1097/QAD.0b013e328359f20f.Massanella M., Negredo E., Puig J. et al. Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery // AIDS. 2012. Vol. 26, No. 18. Р. 2285–2293. doi: https://doi.org/10.1097/QAD.0b013e328359f20f.Lafeuillade A., Assi A., Poggi C. et al. Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial // AIDS Research and Therapy. 2014. Vol. 11, No. 1. Р. 1–6. doi: https://doi.org/10.1186/1742-6405-11-33.Lafeuillade A., Assi A., Poggi C. et al. Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial // AIDS Research and Therapy. 2014. Vol. 11, No. 1. Р. 1–6. doi: https://doi.org/10.1186/1742-6405-11-33.Joly V., Fagard C., Grondin C. et al. Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo) // Antimicrobial agents and chemotherapy. 2013. Vol. 57, No. 2. Р. 758–765. doi: https://doi.org/10.1128/AAC.01662-12.Joly V., Fagard C., Grondin C. et al. Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo) // Antimicrobial agents and chemotherapy. 2013. Vol. 57, No. 2. Р. 758–765. doi: https://doi.org/10.1128/AAC.01662-12.Onwumeh J., Okwundu C. I., Kredo T. Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults // Cochrane Database of Systematic Reviews. 2017. No. 5. doi: https://doi.org/10.1002/14651858.CD009818.pub2.Onwumeh J., Okwundu C. I., Kredo T. Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults // Cochrane Database of Systematic Reviews. 2017. No. 5. doi: https://doi.org/10.1002/14651858.CD009818.pub2.Katlama C., Lambert-Niclot S., Assoumou L. et al. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial // AIDS. 2016. Vol. 30, No. 2. Р. 221–230. doi: https://doi.org/10.1097/QAD.0000000000000894.Katlama C., Lambert-Niclot S., Assoumou L. et al. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial // AIDS. 2016. Vol. 30, No. 2. Р. 221–230. doi: https://doi.org/10.1097/QAD.0000000000000894.Bandera A., Lorenzini P., Taramasso L. et al. The impact of DAA-mediated HCV eradication on CD4+ and CD8+ T lymphocyte trajectories in HIV/HCV coinfected patients: Data from the ICONA Foundation Cohort // Journal of Viral Hepatitis. 2021. Vol. 28, No. 5. Р. 779–786. doi: https://doi.org/10.1111/jvh.13488.Bandera A., Lorenzini P., Taramasso L. et al. The impact of DAA-mediated HCV eradication on CD4+ and CD8+ T lymphocyte trajectories in HIV/HCV coinfected patients: Data from the ICONA Foundation Cohort // Journal of Viral Hepatitis. 2021. Vol. 28, No. 5. Р. 779–786. doi: https://doi.org/10.1111/jvh.13488.Marino A., Zafarana G., Ceccarelli M. et al. Immunological and clinical impact of DAA-Mediated HCV eradication in a cohort of HIV/HCV coinfected patients: Monocentric Italian experience // Diagnostics. 2021. Vol. 11, No. 12. Р. 2336. doi: https://doi.org/10.3390/diagnostics11122336.Marino A., Zafarana G., Ceccarelli M. et al. Immunological and clinical impact of DAA-Mediated HCV eradication in a cohort of HIV/HCV coinfected patients: Monocentric Italian experience // Diagnostics. 2021. Vol. 11, No. 12. Р. 2336. doi: https://doi.org/10.3390/diagnostics11122336.Hunt P.W., Martin J.N., Sinclair E. et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy // Journal of Infectious Diseases. 2011. Vol. 203, No. 10. Р. 1474–1483. doi: https://doi.org/10.1093/infdis/jir060.Hunt P.W., Martin J.N., Sinclair E. et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy // Journal of Infectious Diseases. 2011. Vol. 203, No. 10. Р. 1474–1483. doi: https://doi.org/10.1093/infdis/jir060.Jiménez-Sousa M.Á., Martínez I., Medrano L.M., Fernández-Rodríguez A. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease // Frontiers in immunology. 2018. Vol. 9. Р. 458. doi: https://doi.org/10.3389/fimmu.2018.00458.Jiménez-Sousa M.Á., Martínez I., Medrano L.M., Fernández-Rodríguez A. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease // Frontiers in immunology. 2018. Vol. 9. Р. 458. doi: https://doi.org/10.3389/fimmu.2018.00458.Coelho L., Cardoso S.W., Luz P.M. et al. Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy // Nutrition journal. 2015. Vol. 14, No. 1. Р. 1–9. doi: https://doi.org/10.1186/s12937-015-0072-6.Coelho L., Cardoso S.W., Luz P.M. et al. Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy // Nutrition journal. 2015. Vol. 14, No. 1. Р. 1–9. doi: https://doi.org/10.1186/s12937-015-0072-6.Abraham A.G., Zhang L., Calkins K. et al. Vitamin D status and immune function reconstitution in HIV-infected men initiating therapy in the Multicenter AIDS Cohort Study // AIDS (London, England). 2018. Vol. 32, No. 8. Р. 1069. doi: https://doi.org/10.1097/QAD.0000000000001782.Abraham A.G., Zhang L., Calkins K. et al. Vitamin D status and immune function reconstitution in HIV-infected men initiating therapy in the Multicenter AIDS Cohort Study // AIDS (London, England). 2018. Vol. 32, No. 8. Р. 1069. doi: https://doi.org/10.1097/QAD.0000000000001782.Ancona G., Merlini E., Tincati C. et al. Long-term suppressive cART is not sufficient to restore intestinal permeability and gut microbiota compositional changes // Frontiers in immunology. 2021. Vol. 12. Р. 639291. doi: https://doi.org/10.3389/fimmu.2021.639291.Ancona G., Merlini E., Tincati C. et al. Long-term suppressive cART is not sufficient to restore intestinal permeability and gut microbiota compositional changes // Frontiers in immunology. 2021. Vol. 12. Р. 639291. doi: https://doi.org/10.3389/fimmu.2021.639291.D’Ettorre G., Rossi G., Scagnolari C. et al. Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients // Immunity, inflammation and disease. 2017. Vol. 5, No. 3. Р. 244–260. doi: https://doi.org/10.1002/iid3.160.D’Ettorre G., Rossi G., Scagnolari C. et al. Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients // Immunity, inflammation and disease. 2017. Vol. 5, No. 3. Р. 244–260. doi: https://doi.org/10.1002/iid3.160.Kazemi A., Soltani S., Ghorabi S. et al. Effect of probiotic and synbiotic supplementation on inflammatory markers in health and disease status: A systematic review and meta-analysis of clinical trials // Clinical Nutrition. 2020. Vol. 39, No. 3. Р. 789–819. doi: https://doi.org/10.1016/j.clnu.2019.04.004.Kazemi A., Soltani S., Ghorabi S. et al. Effect of probiotic and synbiotic supplementation on inflammatory markers in health and disease status: A systematic review and meta-analysis of clinical trials // Clinical Nutrition. 2020. Vol. 39, No. 3. Р. 789–819. doi: https://doi.org/10.1016/j.clnu.2019.04.004.Wang J.W., Kuo C.H., Kuo F.C. et al. Fecal microbiota transplantation: Review and update // Journal of the Formosan Medical Association. 2019. Vol. 118. Р. S23-S31. doi: https://doi.org/10.1016/j.jfma.2018.08.011.Wang J.W., Kuo C.H., Kuo F.C. et al. Fecal microbiota transplantation: Review and update // Journal of the Formosan Medical Association. 2019. Vol. 118. Р. S23-S31. doi: https://doi.org/10.1016/j.jfma.2018.08.011.Vujkovic-Cvijin I., Rutishauser R.L., Pao M. et al. Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals // Gut microbes. 2017. Vol. 8, No. 5. Р. 440–450. doi: https://doi.org/10.1080/19490976.2017.1334034.Vujkovic-Cvijin I., Rutishauser R.L., Pao M. et al. Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals // Gut microbes. 2017. Vol. 8, No. 5. Р. 440–450. doi: https://doi.org/10.1080/19490976.2017.1334034.Kang Y., Cai Y. Altered gut microbiota in HIV infection: future perspective of fecal microbiota transplantation therapy // AIDS research and human retroviruses. 2019. Vol. 35, No. 3. Р. 229–235. doi: https://doi.org/10.1089/aid.2017.0268.Kang Y., Cai Y. Altered gut microbiota in HIV infection: future perspective of fecal microbiota transplantation therapy // AIDS research and human retroviruses. 2019. Vol. 35, No. 3. Р. 229–235. doi: https://doi.org/10.1089/aid.2017.0268.Kasang C., Kalluvya S., Majinge C. et al. Effects of prednisolone on disease progression in antiretroviral-untreated HIV infection: a 2-year randomized, double-blind placebo-controlled clinical trial // PLoS One. 2016. Vol. 11, No. 1. Р. e0146678. doi: https://doi.org/10.1371/journal.pone.0146678.Kasang C., Kalluvya S., Majinge C. et al. Effects of prednisolone on disease progression in antiretroviral-untreated HIV infection: a 2-year randomized, double-blind placebo-controlled clinical trial // PLoS One. 2016. Vol. 11, No. 1. Р. e0146678. doi: https://doi.org/10.1371/journal.pone.0146678.Van Welzen B.J., de Vries T.I., Arends J.E. et al. The use of corticosteroids does not influence CD4+ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency // AIDS care. 2019. doi: 10.1080/09540121.2019.1623376.Van Welzen B.J., de Vries T.I., Arends J.E. et al. The use of corticosteroids does not influence CD4+ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency // AIDS care. 2019. doi: 10.1080/09540121.2019.1623376.Jain M.K., Ridker P.M. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms // Nature reviews Drug discovery. 2005. Vol. 4, No.12. Р. 977–987. doi: https://doi.org/10.1038/nrd1901.Jain M.K., Ridker P.M. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms // Nature reviews Drug discovery. 2005. Vol. 4, No.12. Р. 977–987. doi: https://doi.org/10.1038/nrd1901.Funderburg N.T., Jiang Y., Debanne S.M. et al. Rosuvastatin reduces vascular inflammation and T cell and monocyte activation in HIV-infected subjects on antiretroviral therapy // Journal of acquired immune deficiency syndromes. 2015. Vol. 68. No. 4. Р. 396. doi: 10.1097/QAI.000000000000047.Funderburg N.T., Jiang Y., Debanne S.M. et al. Rosuvastatin reduces vascular inflammation and T cell and monocyte activation in HIV-infected subjects on antiretroviral therapy // Journal of acquired immune deficiency syndromes. 2015. Vol. 68. No. 4. Р. 396. doi: 10.1097/QAI.000000000000047.Nakanjako D., Ssinabulya I., Nabatanzi R. et al. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected c ART-treated suboptimal immune responders in U ganda: a randomised crossover placebo-controlled trial // Tropical medicine & international health. 2015. Vol. 20, No. 3. Р. 380–390. doi: 10.1111/tmi.12442.Nakanjako D., Ssinabulya I., Nabatanzi R. et al. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected c ART-treated suboptimal immune responders in U ganda: a randomised crossover placebo-controlled trial // Tropical medicine & international health. 2015. Vol. 20, No. 3. Р. 380–390. doi: 10.1111/tmi.12442.Rizzardi G.P., Harari A., Capiluppi B. et al. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy // The Journal of clinical investigation. 2002. Vol. 109, No. 5. Р. 681–688. doi: https://doi.org/10.1172/JCI14522.Rizzardi G.P., Harari A., Capiluppi B. et al. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy // The Journal of clinical investigation. 2002. Vol. 109, No. 5. Р. 681–688. doi: https://doi.org/10.1172/JCI14522.Lederman M.M., Smeaton L., Smith K.Y. et al. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138 // The Journal of infectious diseases. 2006. Vol. 1, No. 12. Р. 1677–1685. doi: https://doi.org/10.1086/509261.Lederman M.M., Smeaton L., Smith K.Y. et al. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138 // The Journal of infectious diseases. 2006. Vol. 1, No. 12. Р. 1677–1685. doi: https://doi.org/10.1086/509261.Markowitz M., Vaida F., Hare В. et al. The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection // The Journal of infectious diseases. 2010. Vol. 201, No. 9. Р. 1298–1302. doi: https://doi.org/10.1086/651664.Markowitz M., Vaida F., Hare В. et al. The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection // The Journal of infectious diseases. 2010. Vol. 201, No. 9. Р. 1298–1302. doi: https://doi.org/10.1086/651664.

The authors declare that there are no conflicts of interest present.