Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells

Maria J. Buzon, Enrique Martin-Gayo, Florencia Pereyra, Zhengyu Ouyang, Hong Sun, Jonathan Z. Li, Michael Piovoso, Amy Shaw, Judith Dalmau, Nadine Zangger, Javier Martinez-Picado, Ryan Zurakowski, Xu G. Yu, Amalio Telenti, Bruce D. Walker, Eric S. Rosenberg, Mathias Lichterfeld

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Abstract

© 2014, American Society for Microbiology. Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for > 10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls.Weobserved that independently of the timing of treatment initiation, HIV-1DNAin CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1DNAafter long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central- memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for > 10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure.
Original languageEnglish
Pages (from-to)10056-10065
JournalJournal of Virology
Volume88
Issue number17
DOIs
Publication statusPublished - 1 Jan 2014

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    Buzon, M. J., Martin-Gayo, E., Pereyra, F., Ouyang, Z., Sun, H., Li, J. Z., Piovoso, M., Shaw, A., Dalmau, J., Zangger, N., Martinez-Picado, J., Zurakowski, R., Yu, X. G., Telenti, A., Walker, B. D., Rosenberg, E. S., & Lichterfeld, M. (2014). Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. Journal of Virology, 88(17), 10056-10065. https://doi.org/10.1128/JVI.01046-14