Nutritional formula linked to reduced CD4 cell loss in untreated people

A complex nutritional formula may help slow CD4 cell decline and reduce immune activation in people with HIV who have not yet started antiretroviral therapy, according to an international study presented this week at the 49^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.

Nutrition clearly contributes to good health, but the multiple ways in which various types of nutrients affect immune function and other biological processes are not fully understood.

To explore this issue, Pedro Cahn and fellow investigators with the BITE study looked at whether a nutritional formula called NR100157 could reduce loss of CD4 cells in HIV-positive people who are not on antiretroviral treatment.

The NR100157 formula contains multiple ingredients individually shown to have beneficial effects on immune function:

• Prebiotic oligosaccharides, or chains of simple sugars, help maintain healthy flora (natural bacteria) in the gut.
• Bovine colostrum (breast fluid produced prior to milk) and long-chain poly-unsaturated fatty acids improve the integrity and decrease the permeability of the gut lining. This helps prevent bacteria from leaking out and triggering systemic immune activation, thought to be one mechanism of CD4 cell loss.
• N-acetyl cysteine helps maintain the body's supply of glutathione, an important antioxidant. The product also includes an array of micronutrients including vitamins and minerals.

This controlled clinical trial was designed to include 800 HIV-positive adults in Argentina, Australia, Brazil, Italy, the Netherlands, Thailand, the UK and the US. Half the participants would be randomly assigned to take the NR100157 formula for one year, whilst the remainder received a control product with the same amount of calories and protein but without the active ingredients.

The study was stopped early with only 340 enrollees after a planned interim analysis showed a significant benefit in the NR100157 group and no safety concerns.

The participants enrolled up to that point were mostly men (just over 80%), were about 40 years old on average, and had been infected with HIV for a little over a year. The median CD4 count was approximately 400 cells/mm³ and viral load was about 32,000 copies/ml. Participants did not yet require antiretroviral therapy at study entry; if investigators determined they needed to go on treatment, they were dropped from the nutrition study.

Participants receiving NR100157 lost significantly fewer CD4 cells over the follow-up period. Those taking the inactive product experienced a decrease of 68 cells/mm³ per year (within the expected range of 50 to 70 cells annually), compared with 28 cells/mm³ per year for NR100157 recipients. There were no significant differences in CD4 percentage, CD8 cell count, or CD4/CD8 ratio. Plasma viral load remained stable and similar in both groups.

NR100157 was well tolerated overall and reported adherence was high, at 85%. However, about 60% discontinued therapy early, often due to adverse events (about 13%) or because they needed to start antiretroviral therapy (about 16%). Gastrointestinal symptoms - mainly bloating and gas - were the most frequent reason for adverse events drop-outs, and were more common in the NR100157 arm.

The BITE investigators concluded that NR100157 significantly slows down the decline in CD4 count in HIV positive people not taking antiretroviral therapy. "These findings show the potential for nutritional based strategies to become an integral part of disease management," they suggested.

The product’s developer, Danone, better known as a market leader in dairy foods, said today that it plans to develop NR100157 into a nutritional product which can be marketed within several years.