The Immunomodulatory Nutritional Intervention NR100157 Reduced CD4+ T-Cell Decline and Immune Activation: A 1-Year Multicenter Randomized Controlled Double-Blind Trial in HIV-Infected Persons Not Receiving Antiretroviral Therapy (The BITE Study)

Background. The immunomodulatory nutritional product NR100157 was developed for human immunodeficiency virus (HIV)-infected individuals. We hypothesized that targeting the compromised gastrointestinal tract of HIV-infected individuals would result in systemic immunological benefits. Methods. In a multicenter, randomized, controlled, double-blind trial, 340 HIV-1-positive adults not on antiretroviral therapy, with CD4(+) T-cell counts <800/mu L, were given either NR100157 or an isocaloric and isonitrogenous control for 52 weeks. Primary outcome was CD4(+) T-cell count. Secondary outcomes included plasma viral load (pVL), safety, and tolerability. In a pilot study (n = 20), levels of CD4(+) CD25(+) and CD8(+) CD38(+) activation were measured (n = 20). The trial is registered at the Dutch Trial Register (NTR886) and ISRCTN81868024. Results. At 52 weeks, CD4(+) T-cell decline showed a 40-cell/mu L difference (P =.03) in the intention-to-treat population in favor of the immunomodulatory NR100157 (control vs active, -68 +/- 15 vs -28 +/- 16 cells/mu L/year). The change in pVL from baseline was similar between groups (P =.81). In the pilot study, the percentage of CD4(+) CD25(+) was lower in the active group (P <.05) and correlated with changes in CD4(+) T-cell count (r = -0.55, P <.05). The percentage of CD8(+) CD38(+) levels was unaffected. Conclusions. The specific immunonutritional product NR100157 significantly reduces CD4(+) decline in HIV1-infected individuals, and this is associated with decreased levels of CD4(+) CD25(+). (This nutritional intervention is likely to affect local gut integrity and gut-associated lymphoid tissue homeostasis, which in turn translates positively to systemic effects.)