Precocious immunosenescence in HIV infection: effect of chronic viral persistence or antirretroviral therapy?




Immunosenescence; HIV; Aging; Antiretroviral therapy highly.


Antiretroviral therapies have increased the life expectancy of people living with HIV, however a major concern is the increase in comorbidities,  such as cardiovascular, metabolic bone and neurodegenerative diseases, which are the result of an immunosensitivity phenomenon associated with the cellular aging of the system immunological, called immunossenescence. This article aims to analyze the main factors promoting this event in HIV infection, discussing whether it is the result of chronic viral persistence or antiretroviral therapy. This is a review of the literature developed from consultation with the Virtual Health Library, using the MEDLINE and LILACS databases. The results showed that the HIV virus has the potential to influence the senescence of immune cells by reducing the number of CD4+ T lymphocytes, increasing CD8+ T lymphocytes, with shorter telomeres, and with a low rate of renewal due to deficiency in the production of its precursors. In addition, treatment with antiretrovirals also has the ability to accelerate the senescence of immune cells, either by the action of NRTIs on the enzyme telomerase or on the polymerase of mitochondria or by producing oxidative stress. Therefore, the evidence suggests that both processes can contribute to the accelerated establishment of a low-grade chronic inflammatory phenotype resulting in significant early immune remodeling in HIV infection.


Alejos, B., Stella-Ascariz, N., Montejano, R., Rodriguez-Centeno, J., Schwimmer, C., Bernardino, J. I., Rodes, B., Esser, S., Goujard, C., Sarmento-Castro, R., De Miguel, R., Esteban-Cantos, A., Wallet, C., Raffi, F., Arribas, J. R., & NEAT 001/ANRS 143 Study Group (2019). Determinants of blood telomere length in antiretroviral treatment-naïve HIV-positive participants enrolled in the NEAT 001/ANRS 143 clinical trial. HIV medicine, 20(10), 691–698.

Appay, V., & Sauce, D. (2017). Assessing immune aging in HIV-infected patients. Virulence, 8(5), 529–538.

Bauer, M. E., Wieck, A., Petersen, L. E., & Baptista, T. S. (2015). Neuroendocrine and viral correlates of premature immunosenescence. Annals of the New York Academy of Sciences, 1351, 11–21.

Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2017). Human T cell immunosenescence and inflammation in aging. Journal of leukocyte biology, 102(4), 977–988.

Bellon, M., & Nicot, C. (2017). Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection. Viruses, 9(10), 289.

Buggert, M., Japp, A. S., & Betts, M. R. (2019). Everything in its right place: resident memory CD8+ T cell immunosurveillance of HIV infection. Current opinion in HIV and AIDS, 14(2), 93–99.

Côté, H. C., Soudeyns, H., Thorne, A., Alimenti, A., Lamarre, V., Maan, E. J., Sattha, B., Singer, J., Lapointe, N., Money, D. M., Forbes, J., CIHR Emerging Team in HIV therapy, aging (CARMA), Wong, J., Bitnun, A., Samson, L., Brophy, J., Burdge, D., Pick, N., van Schalkwyk, J., Montaner, J., … Janssen, P. (2012). Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia. PloS one, 7(7), e39266.

Deeks S. G. (2011). HIV infection, inflammation, immunosenescence, and aging. Annual review of medicine, 62, 141–155.

Deeks, S. G., Overbaugh, J., Phillips, A., & Buchbinder, S. (2015). HIV infection. Nature reviews. Disease primers, 1, 15035.

Desai, S., & Landay, A. (2010). Early immune senescence in HIV disease. Current HIV/AIDS reports, 7(1), 4–10.

Effros R. B. (2016). The silent war of CMV in aging and HIV infection. Mechanisms of ageing and development, 158, 46–52.

Erlandson, K. M., Allshouse, A. A., Jankowski, C. M., Lee, E. J., Rufner, K. M., Palmer, B. E., Wilson, C. C., MaWhinney, S., Kohrt, W. M., & Campbell, T. B. (2013). Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. The Journal of infectious diseases, 208(2), 249–259.

Fastenackels, S., Sauce, D., Vigouroux, C., Avettand-Fènoël, V., Bastard, J. P., Fellahi, S., Nailler, L., Arezes, E., Rouzioux, C., Warszawski, J., Viard, J. P., Appay, V., & ANRS Co19 COVERTE Study Group (2019). HIV-mediated immune aging in young adults infected perinatally or during childhood. AIDS (London, England), 33(11), 1705–1710.

Figueirêdo Júnior, E. C., Ribeiro, A. D. ., Cruz , J. H. de A. ., Marques, M. H. V. P. ., Marinho, S. A. ., & Pereira, J. V. . (2020). Epidemiological profile of Aids cases reported in Brazil from 2009 to 2019. Research, Society and Development, 9(9), e302997233.

Franzese, O., Barbaccia, M. L., Bonmassar, E., & Graziani, G. (2018). Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence. Chemotherapy, 63(2), 64–75. Advance online publication.

Fülöp, T., Herbein, G., Cossarizza, A., Witkowski, J. M., Frost, E., Dupuis, G., Pawelec, G., & Larbi, A. (2017). Cellular Senescence, Immunosenescence and HIV. Interdisciplinary topics in gerontology and geriatrics, 42, 28–46.

Gianesin, K., Noguera-Julian, A., Zanchetta, M., Del Bianco, P., Petrara, M. R., Freguja, R., Rampon, O., Fortuny, C., Camós, M., Mozzo, E., Giaquinto, C., & De Rossi, A. (2016). Premature aging and immune senescence in HIV-infected children. AIDS (London, England), 30(9), 1363–1373.

Guaraldi, G., Franconi, I., Milic, J., Besutti, G., Pintassilgo, I., Scaglioni, R., Ligabue, G., Riva, N., Raimondi, A., Menozzi, M., Carli, F., Zona, S., Santoro, A., Malagoli, A., Borghi, V., Torricelli, P., Cossarizza, A., & Mussini, C. (2019). Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV. Open forum infectious diseases, 6(10), ofz435.

Johnson, A. A., Shokhirev, M. N., & Shoshitaishvili, B. (2019). Revamping the evolutionary theories of aging. Ageing research reviews, 55, 100947.

Kaplan-Lewis, E., Aberg, J. A., & Lee, M. (2017). Aging with HIV in the ART era. Seminars in diagnostic pathology, 34(4), 384–397.

Law, K. M., Satija, N., Esposito, A. M., & Chen, B. K. (2016). Cell-to-Cell Spread of HIV and Viral Pathogenesis. Advances in virus research, 95, 43–85.

Lee, S. A., Sinclair, E., Hatano, H., Hsue, P. Y., Epling, L., Hecht, F. M., Bangsberg, D. R., Martin, J. N., McCune, J. M., Deeks, S. G., & Hunt, P. W. (2014). Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging. PloS one, 9(2), e89444.

Leeansyah, E., Cameron, P. U., Solomon, A., Tennakoon, S., Velayudham, P., Gouillou, M., Spelman, T., Hearps, A., Fairley, C., Smit, d., Pierce, A. B., Armishaw, J., Crowe, S. M., Cooper, D. A., Koelsch, K. K., Liu, J. P., Chuah, J., & Lewin, S. R. (2013). Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. The Journal of infectious diseases, 207(7), 1157–1165.

Lori F. (2008). Treating HIV/AIDS by reducing immune system activation: the paradox of immune deficiency and immune hyperactivation. Current opinion in HIV and AIDS, 3(2), 99–103.

Maeda, K., Das, D., Kobayakawa, T., Tamamura, H., & Takeuchi, H. (2019). Descoberta e desenvolvimento de agentes terapêuticos anti-HIV: progresso em direção a medicamentos para HIV aprimorados. Tópicos atuais em química medicinal , 19 (18), 1621-1649.

McHugh, D., & Gil, J. (2018). Senescence and aging: Causes, consequences, and therapeutic avenues. The Journal of cell biology, 217(1), 65–77.

Nagai, S., & Azuma, M. (2019). The CD28-B7 Family of Co-signaling Molecules. Advances in experimental medicine and biology, 1189, 25–51.

Nasi, M., De Biasi, S., Gibellini, L., Bianchini, E., Pecorini, S., Bacca, V., Guaraldi, G., Mussini, C., Pinti, M., & Cossarizza, A. (2017). Ageing and inflammation in patients with HIV infection. Clinical and experimental immunology, 187(1), 44–52.

Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017). Interleukin-7 and Immunosenescence. Journal of immunology research, 2017, 4807853.

Paghera, S., Quiros-Roldan, E., Sottini, A., Properzi, M., Castelli, F., & Imberti, L. (2019). Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life. Immunity & ageing : I & A, 16, 26.

Pathai, S., Lawn, S. D., Gilbert, C. E., McGuinness, D., McGlynn, L., Weiss, H. A., Port, J., Christ, T., Barclay, K., Wood, R., Bekker, L. G., & Shiels, P. G. (2013). Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study. AIDS (London, England), 27(15), 2375–2384.

Payne, B. A., Wilson, I. J., Hateley, C. A., Horvath, R., Santibanez-Koref, M., Samuels, D. C., Price, D. A., & Chinnery, P. F. (2011). Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature genetics, 43(8), 806–810.

Phetsouphanh, C., Aldridge, D., Marchi, E., Munier, C., Meyerowitz, J., Murray, L., Van Vuuren, C., Goedhals, D., Fidler, S., Kelleher, A., Klenerman, P., & Frater, J. (2019). Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers. Frontiers in immunology, 10, 1844.

Quiros-Roldan, E., Properzi, M., Paghera, S., Raffetti, E., Castelli, F., & Imberti, L. (2020). Factors associated with immunosenescence during early adulthood in HIV-infected patients after durable efficient combination antiretroviral therapy. Scientific reports, 10(1), 10057.

Sharp, P. M., & Hahn, B. H. (2011). Origins of HIV and the AIDS pandemic. Cold Spring Harbor perspectives in medicine, 1(1), a006841.

Singh, M. V., Kotla, S., Le, N. T., Ae Ko, K., Heo, K. S., Wang, Y., Fujii, Y., Thi Vu, H., McBeath, E., Thomas, T. N., Jin Gi, Y., Tao, Y., Medina, J. L., Taunton, J., Carson, N., Dogra, V., Doyley, M. M., Tyrell, A., Lu, W., Qiu, X., … Abe, J. I. (2019). Senescent Phenotype Induced by p90RSK-NRF2 Signaling Sensitizes Monocytes and Macrophages to Oxidative Stress in HIV-Positive Individuals. Circulation, 139(9), 1199–1216.

Smith, R. L., de Boer, R., Brul, S., Budovskaya, Y., & van Spek, H. (2013). Premature and accelerated aging: HIV or HAART?. Frontiers in genetics, 3, 328.

Sokoya, T., Steel, H. C., Nieuwoudt, M., & Rossouw, T. M. (2017). HIV as a Cause of Immune Activation and Immunosenescence. Mediators of inflammation, 2017, 6825493.

Solomon, A., Tennakoon, S., Leeansyah, E., Arribas, J., Hill, A., Van Delft, Y., Moecklinghoff, C., & Lewin, S. R. (2014). No difference in the rate of change in telomere length or telomerase activity in HIV-infected patients after three years of darunavir/ritonavir with and without nucleoside analogues in the MONET trial. PloS one, 9(11), e109718.

Tonet, A. C., & de Tolêdo Nóbrega, O. (2008). Imunossenescência: a relação entre leucócitos, citocinas e doenças crônicas. Revista Brasileira de Geriatria e Gerontologia, 11(2), 259-273.

Tsoukas C. (2014). Immunosenescence and aging in HIV. Current opinion in HIV and AIDS, 9(4), 398–404.

van Marle, G., Church, D. L., van der Meer, F., & Gill, M. J. (2018). Combating the HIV reservoirs. Biotechnology & genetic engineering reviews, 34(1), 76–89.

Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and molecular allergy : CMA, 15, 21.

Vosgerau, D. S. A. R., & Romanowski, J. P. (2014). Estudos de revisão: implicações conceituais e metodológicas. Revista diálogo educacional, 14(41), 165-189.

Yoshimura K. (2017). Current status of HIV/AIDS in the ART era. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 23(1), 12–16.

Zhang, H., Puleston, D. J., & Simon, A. K. (2016). Autophagy and Immune Senescence. Trends in molecular medicine, 22(8), 671–686.



How to Cite

Meireles, J. V. C. ., & Brito, M. de V. (2020). Precocious immunosenescence in HIV infection: effect of chronic viral persistence or antirretroviral therapy?. Research, Society and Development, 9(9), e592997436.



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