Selenium supplementation induces changes in body composition, increases CD4+ T cells frequency and is associated with the expression of genes responsible of naïve and memory CD8+ T cells function on treated HIV-infected individuals.
Background & aim: Micronutrient deficiencies, particularly those of zinc and selenium, are common in persons living with human immunodeficiency virus (PLWHIV), and have been associated with the development of non-AIDS related comorbidities, impaired immune system function, HIV disease progression and mortality. The implementation of intervention strategies on clinically stable long-term-treated PLWHIV could bring potential benefits on impeding or delaying the onset of non-AIDS associated comorbidities, improving their health status and overall quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density (BMD), lipids profile, glucose and immune system activation and function on PLWHIV on antiretroviral therapy (ART) without metabolic diseases. Methods: This pilot trial was composed of 60 PLWHIV on ART who were randomly assigned to either zinc, selenium, zinc + selenium supplementation or to a control group. Daily supplementation was prescribed during 6 months as follows: the zinc group received 30 mg of zinc gluconate, the selenium group received 200 mcg of selenium yeast and the zinc + selenium group received both micronutrients at the same doses and presentations. Individuals in the control group were followed during the same time without any nutritional supplementation. Body composition (weight, body mass index [BMI], fat mass and muscle mass), BMD, blood pressure, blood biochemical parameters (cholesterol, glucose and triglycerides), serum zinc and selenium concentrations, CD4+ T cell count and CD4+ and CD8+ T cells immune activation were assessed before and after supplementation. One individual of each supplementation group and one of the control group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p=0.03), fat mass in kg (p=0.03) and percentage (p=0.02), as well as trunk fat (p=0.01), were significantly decreased after selenium supplementation. No changes were observed for body composition, BMD, biochemical determinations or blood pressure on the other intervention groups after supplementation (p>0.05 in all cases). The CD4+ T cells frequency and count significantly increased after selenium and zinc supplementation (p=0.03, p=0.05 respectively). CD4+ and CD8+ T-cell immune activation did not change after supplementation (p>0.05 in both cases). On the single cell transcriptome analysis, zinc and selenium supplementation significantly change de expression of genes associated with the function of naive and memory CD8+ T cells (adjusted p<0.05 in all cases). Conclusions: Selenium supplementation have beneficial effects on the body composition, while zinc and selenium supplementation increased CD4+ T cell replenishment of PLWHIV on long-term ART without metabolic diseases. Additionally, zinc and selenium supplementation modified the expression of genes associated with the function of naive and memory CD8+ T cells. Zinc and selenium supplementation are a simple, low-cost, and safe nutritional treatment that represents a complementary intervention to improve the health status and increase the quality of life of clinically stable PLWHIV  without metabolic diseases. Registered: Under ClinicalTrails.gov identifier NCT03421314 Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from EDTA-anticoagulated peripheral blood by density gradient centrifugation. Vials with 25 million PBMCs were cryopreserved until used. Blood samples taken at baseline and after six months of treatment were used for targeted scRNA-seq library preparation; the samples came from a control patient (with no supplementation) and three patients that had received zinc, selenium, or zinc plus selenium supplementation, respectively.