Longitudinal evaluation of regulatory T-cell dynamics on HIV-infected individuals during the first 2 years of therapy

Objectives: A sizeable percentage of individuals infected by HIV and on antiretroviral therapy (ART) fail to increase their CD4+ T-cells to satisfactory levels. The percentage of regulatory T-cells (Tregs) has been suggested to contribute to this impairment. This study aimed to address this question and to expand the analysis of Tregs subpopulations during ART. Design: Longitudinal follow-up of 81 HIV-infected individuals during the first 24 months on ART. Methods: CD4+ T-cell counts, Tregs percentages, and specific Tregs subpopulations were evaluated at ART onset, 2, 6, 9, 12, 16, 20, and 24 months of ART (five individuals had no Tregs information at baseline). Results: The slope of CD4+ T-cell recovery was similar for individuals with moderate and with severe lymphopenia at ART onset. No evidence was found for a contribution of the baseline Tregs percentages on the CD4+ T-cell counts recovery throughout ART. In comparison to uninfected individuals, Tregs percentages were higher at ART onset only for patients with less than 200?cells/µl at baseline and decreased afterwards reaching normal values. Within Tregs, the percentage of naive cells remained low in these patients. Reduced thymic export and increased proliferation of Tregs vs. conventional CD4+ T cells might explain these persistent alterations. Conclusion: No effect of Tregs percentages at baseline was detected on CD4+ T-cell recovery. However, profound alterations on Tregs subpopulations were consistently observed throughout ART for patients with severe lymphopenia at ART onset.The work was funded by the Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and cofinanced by the Programa Operacional Novo Norte (ON.2 – O Novo Norte) under the Quadro de Referencia Estratégica Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER). A FCT fellowship, under the Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE), was given to C.N. (SFRH/BPD/65380/2009) and to R.Rb-S. (PD/BD/106047/2015; fellowship in the context of the Inter-University Doctoral Programme in Ageing and Chronic Disease, a FCT PhD Program