By Liz Highleyman

Pedro Cahn and colleagues with the international BITE study aimed to determine whether a combination nutritional formula could reduce CD4 cells loss in people on ART.

The randomized controlled trial was designed to include 800 HIV positive participants in Argentina, Australia, Brazil, Italy, the Netherlands, Thailand, the U.K., and the U.S. Half were randomly assigned to take the nutritional formula, known as NR100157, for 1 year, while the other half received a control product containing the same amount of calories and protein, but without the active ingredients.

NR100157 contains several components that individually have demonstrated beneficial effects on immune function in previous studies:

	Prebiotic oligosaccharides: chains of simple sugars that help maintain healthy flora, or balance of bacteria in the gut;
	N-acetyl cysteine: a modified amino acid that helps maintain the body's supply of glutathione, a key antioxidant;
	Bovine colostrum: nutrient- and antibody-rich fluid produced prior to milk;
	Omega-3 long-chain polyunsaturated fatty acids: molecules shown to improve the integrity of the gut, which prevents bacteria from leaking out and triggering systemic immune activation;
	Micronutrients including vitamins and minerals.

The study was stopped early after a planned interim analysis showed significant immunological benefit in the NR100157 arm and no notable safety concerns.

The 340 participants enrolled up to that point (168 in the NR100157 arm, 172 in the control arm) were about 80% men with an average age of 40 years. The average duration of HIV infection was about 420 days, the median CD4 count was about 420 cells/mm3, and viral load was about 32,000 copies/mL.

Based on their CD4 count, the participants did not yet need to be on ART at the time of enrollment; if site investigators determined they needed to start, they discontinued the nutrition study.

Results

	Participants in the NR100157 arm lost significantly fewer CD4 cells per year than those in the control arm (-28 vs -68 cells/mm3, respectively; expected loss for untreated people with HIV 50-70 cells/mm3 annually).
	There were no significant differences between the 2 arms with regard to CD4 percentage, CD8 cell count, or CD4/CD8 ratio.
	Plasma viral load remained stable, and similar, in both groups.
	Adherence was high in both arms, at 85%.
	About 60% of participants discontinued the study early for various reasons:
	Adverse events: 30 patients in NR100157 arm vs 14 in control arm; Needed to start ART: 25 vs 29, respectively; Lost to follow-up: 20 vs 17, respectively; Withdrew consent: 17 vs 20, respectively; Other reasons: 16 vs 9 respectively.
	Most withdrawals for adverse events were due to gastrointestinal symptoms (mainly bloating and gas), which were more common in the NR100157 arm.
	There were no differences between arms in the rates of other types of adverse events.
	No product-related serious adverse events or grade 3-4 laboratory abnormalities were observed.

Based on these results, the investigators concluded, "NR10057 significantly slows down the decline in CD4+ T-cell count in HIV-infected patients not on HAART."

"These findings show the potential for nutritional based strategies to become an integral part of disease management," they added. "Further studies are needed in order to establish clinical relevance of this approach."

AMC, Amsterdam, Netherlands; Chelsea Westminster Hosp. NHS Fndn. Trust, London, UK; Federal Univ. of San Paulo, San Paulo, Brazil; Univ. of Milan, Milan, Italy; Utrecht Inst. Pharma. Sc., Utrecht, Netherlands; Nutricia Advanced Med. Nutrition, Wageningen, Netherlands; St Lukes-Roosevelt Hosp. Ctr., New York, NY; Fundación Huésped, Buenos Aires, Argentina.

9/22/09

References
J Lange, B Gazzard, R Diaz, and others. Reduced CD4+ T cell decline and immune activation by NR100157, a specific multi-targeted nutritional intervention, in HIV-1 positive adults not on antiretroviral therapy (BITE). 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract H-1230b.