Effective Treatment of Patients Experiencing Primary, Acute HIV Infection Decreases Exhausted/Activated CD4+ T Cells and CD8+ T Memory Stem Cells

有效治疗原发性急性 HIV 感染患者可减少耗竭/活化的 CD4+ T 细胞和 CD8+ T 记忆干细胞。

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作者:Domenico Lo Tartaro ,Antonio Camiro-Zúñiga ,Milena Nasi ,Sara De Biasi ,Marco A Najera-Avila ,Maria Del Rocio Jaramillo-Jante ,Lara Gibellini ,Marcello Pinti ,Anita Neroni ,Cristina Mussini ,Luis E Soto-Ramírez ,Juan J Calva ,Francisco Belaunzarán-Zamudio ,Brenda Crabtree-Ramirez ,Christian Hernández-Leon ,Juan L Mosqueda-Gómez ,Samuel Navarro-Álvarez ,Santiago Perez-Patrigeon ,Andrea Cossarizza

Abstract

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.

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