Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4+ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders

Abstract

AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4⁺ T and CD8⁺ T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1β level was significantly decreased, while TNF-β was significantly increased (P < 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly (P < 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased (P < 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4⁺ T cell count with levels of DAO (r = -0.343, P = 0.004), D-lactate (r = -0.250, P = 0.037), respectively, and a significantly positive correlation of IL-1β level with levels of DAO (r = 0.445, P < 0.001), D-lactate (r = 0.523, P < 0.001), and LPS (r = 0.622, P < 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.

Keywords: HIV/AIDS; enteral nutrition; immunological non-response; inflammation; intestinal barrier function.

Figure 1

Workflow of the patient recruitment and nutrition intervention procedure. (A) Flow diagram of patient recruitment in the trial. (B) The procedures of nutritional intervention, sampling, and analyses.

Figure 2

Changes in immune cells after the nutritional intervention. (A) CD4⁺ T cell count, (B) CD8⁺ T cell count, (D) WBC, and (F) neutrophils were significantly increased, while (C) CD4/CD8 ratio, (E) TCL, and (G) NLR did not change significantly. Statistically significant differences are indicated as *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 3

Changes in serum levels of cytokines after the nutritional intervention. After nutritional treatment, only the IL-1β (E) level decreased significantly, and the serum TNF-β (B) level was significantly higher than that before nutritional intervention. Serum levels of (A) TNF-α, (C) IP-10, (D) IL-1α, (F) MCP-1, (G) IL-6, (H) CD14, (I) D-dimer, and (J) CRP, were not significantly changed. Statistically significant differences are indicated as **P < 0.01, and ***P < 0.001.

Figure 4

Changes in intestinal barrier function after the nutritional intervention. The serum levels of DAO (A), D-lactate (B), and LPS (C) were significantly decreased in AIDS patients with poor immune reconstitution after three months of nutritional treatment. Statistically significant differences are indicated as ***P < 0.001.

Figure 5

Changes in nutritional status after the nutritional intervention. After pre-digested enteral nutritional supplements were given, the nutritional indicators of patients, including W (A), BMI (B), ALB (D), Hb (F), were significantly increased. TP (C) and PA (E) were not significantly changed. Statistically significant differences are indicated *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 6

Correlation between intestinal barrier function markers and CD4⁺ T cell count or IL-1β level. CD4⁺ T cell counts were significantly negatively correlated with the serum levels of DAO (A) and D-lactate (B), but not significantly negatively correlated with the serum level of LPS (C). The IL-1β level was significantly positively correlated with the serum levels of DAO (D), D-lactate (E), and LPS (F).