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)
P Cahn, K Ruxrungtham, B Gazzard, R S Diaz, A Gori, D P Kotler, A Vriesema, N A Georgiou, J Garssen, M Clerici, J M A Lange, (BTE) Blinded Nutritional Study for Immunity and Tolerance Evaluation Study Team, I Cassetti, G Reboredo, W Vasen, P Cahn, J Anderson, N Bodsworth, T Read, N Roth, C Workman, C Arns da Cunha, M Caseiro, Guilherme Álvaro, J Suleiman, Brasilmed Assistência Médica, R S Diaz, G Rizzardini, T Quirino, Busto Arsizio, A Gori, M Clerici, A van Eeden, M van der Ende, J Prins, C Richter, J Lange, M Fisher, A Winston, D Bray, K Chahour, B Gazzard, K Ruxrungtham, C Brinson, S Brown, C Cohen, A LaMarca, V Sharp, D P Kotler, L Sloan, K Ben Amor, J van de Berg, H Bouritius, B Draijer, J Garthoff, A van Hees, A van Helvoort, M Hoijer, J Knol, B Van't Land, B Mourmans, K van Norren, J Raijmakers, S Ringler, F Sieders, J van der Mooren, E Sliwinski, S Swinkels, C Verduyn, C Verhaart, A P Vos, G van Wijhe, H van der Woude, Christine Wanke, Renger Witkamp, Jos Twisk, P Cahn, K Ruxrungtham, B Gazzard, R S Diaz, A Gori, D P Kotler, A Vriesema, N A Georgiou, J Garssen, M Clerici, J M A Lange, (BTE) Blinded Nutritional Study for Immunity and Tolerance Evaluation Study Team, I Cassetti, G Reboredo, W Vasen, P Cahn, J Anderson, N Bodsworth, T Read, N Roth, C Workman, C Arns da Cunha, M Caseiro, Guilherme Álvaro, J Suleiman, Brasilmed Assistência Médica, R S Diaz, G Rizzardini, T Quirino, Busto Arsizio, A Gori, M Clerici, A van Eeden, M van der Ende, J Prins, C Richter, J Lange, M Fisher, A Winston, D Bray, K Chahour, B Gazzard, K Ruxrungtham, C Brinson, S Brown, C Cohen, A LaMarca, V Sharp, D P Kotler, L Sloan, K Ben Amor, J van de Berg, H Bouritius, B Draijer, J Garthoff, A van Hees, A van Helvoort, M Hoijer, J Knol, B Van't Land, B Mourmans, K van Norren, J Raijmakers, S Ringler, F Sieders, J van der Mooren, E Sliwinski, S Swinkels, C Verduyn, C Verhaart, A P Vos, G van Wijhe, H van der Woude, Christine Wanke, Renger Witkamp, Jos Twisk
Abstract
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/µL, 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/µL difference (P = .03) in the intention-to-treat population in favor of the immunomodulatory NR100157 (control vs active, -68 ± 15 vs -28 ± 16 cells/µL/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 HIV-1-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.) Clinical Trials Registration. ISRCTN81868024.
Keywords: CD4 decline; NR100157; immune activation; immunonutrition.
Source: PubMed