The effects of nutrient supplementation on CD4 T Cell subsets in Zambian adults

Abstract

Background: Although human immunodeficiency virus (HIV) infection is characterized by the progressive depletion of CD4+ T cells, information on the prognostic value of T cell subsets and their response to nutritional intervention is scarce. Objective: To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), to assess the impact of nutritional interventions on T-cell subsets in in vitro and in vivo and to establish the pattern of T-cell distribution in a healthy population. Methods: Five studies were conducted that is, cross-section (HIV-negative adults), retrospective (NUSTART HIV-infected adults), randomised double blind (NUSTART HIV-infected adults), case-control (HIV-infected and HIV-negative adults) and the in vitro selenium dose response study (HIV-negative adults) between April 2013 and May 2015. Immunophenotyping was undertaken to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, 47, Ki67, CD25 and HLA-DR. Results: In the cross section study of 51 healthy adults, the majority of the CD4+ T- cells were naïve and least being cells expressing proliferating marker (Ki67). Retrospective results for the 267 records reviewed showed that there was a significant increase in total CD4 count at p<0.0001 from baseline to twelve weeks of receiving ART plus nutritional support. For the randomised double blind study, among 181 adults enrolled, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group. Case-control results for 50 healthy adults and 50 HIV-infected adults receiving ART treatment plus nutritional intervention for three months showed that by three months T-cells were not comparable to the healthy population. And lastly, in the in vitro selenium dose response study, most of CD4 and CD8 T cell subsets showed significant response to selenium. These results mean that selenium might have transcriptional effects. Conclusions: Although we found that high naïve CD4+ and high senescent CD8+ T cells were not protective against early mortality in HIV-infected adults, most of the T cells in the healthy population equally were naïve. Thus, measuring specific CD4+ T-cell subsets should be considered for prognostic significance in patients initiating ART in Zambia. Furthermore, although there was some good response in the in vitro study, only thymic output responded to this nutritional intervention.