Effect of a nutritional intervention on CD4+ T cell decline in HIV-1-positive adults not on antiretroviral therapy: A multicentre, randomized, controlled, double-blind clinical trial (BITE), with 52 weeks of follow-up

Objective: Based upon proof-of-concept studies with different nutritional modules, we developed a nutritional formulation targeting immune status, gut integrity, oxidative stress, and nutritional status. Here, we tested whether the complete formulation positively affects CD4+decline in early HIV infection. Methods: In a randomized, controlled, double-blind, clinical trial, executed at 31 sites worldwide, we enrolled 340 HIV-1 positive adults with CD4+count <800/mm3and not anticipated to start HAART within the next 6 months. Subjects were assigned to the formulation, containing specific oligosaccharides, n3-PUFAs, colostrum, NAC and a vitamin/ mineral mix or an isocaloric/isonitrogenous control for one year. Primary outcome was change from baseline in CD4+count. Secondary parameters included plasma viral load (pVL), safety and tolerability. All analyses (repeated mixed model) were by ITT. Results: At 52 weeks, CD4+decline showed a significant difference of 40 cells/mm3 (p=0.030) in favor of the nutritional formulation (68 versus 28 cells/mm3/year). Furthermore, a significantly improved slope (p=0.025) of CD4+decline was shown in this group compared to control. pVL was not different in both groups (p=0.811). Compliance of both formulations was over 80% of prescribed dose. 143 subjects completed the study (60 nutritional formulation, 83 control); most common reason for discontinuation was start HAART (protocol-defined end point). Other reasons were 'lost to follow-up', 'withdrew informed consent' and 'adverse events'. The formulation led to temporary mild to moderate GI complaints without clinically relevant safety concerns. Conclusions: This study shows a significant positive effect of the nutritional formulation on reduction in CD4+decline in HIV-1 infection. No clinically relevant safety issues occurred, including adverse events and blood parameters. Administration of this nutritional formulation may be a beneficial approach for HIV-1 infected individuals not on HAART, which warrants further investigation.