provided) Studies in patients with HIV infection have revealed that serum micronutrient levels are often below normal levels particularly for vitamins A, B12, E and for selenium. Some studies have correlated low micronutrient levels with more rapid progression of HIV infection. Intervention trials with micronutrients are extremely difficult to carry out in persons with HIV for the following reasons : a large percentage of HIV/AIDS patients are already taking nutritional supplements in an uncontrolled manner, some in large doses; intake of micronutrients in food varies greatly among persons with HIV infection; there are complex ethical issues surrounding a placebo controlled trial of micronutrients in the HIV/AIDS population; it would be difficult to maintain a micronutrient intervention study during the years of progression of HIV infection; and current and rapidly changing anti-retroviral therapies will alter the natural history of HIV, making it complex to separate out the effects of micronutrient intervention. Yet, micronutrient supplements might play an important role in improving overall nutritional status and slowing the progression of HIV infection. The Simian immunodeficiency virus (SIV) produces an infection in juvenile rhesus monkeys that is remarkably similar to that caused by HIV in humans including, as we have found recently, serum micronutrient deficiencies despite an apparently adequate intake. SIV also causes a wasting condition similar to that seen in young persons with HIV. Because of the rapid progression in SIV, and the clear end points of nutritional parameters, biological markers, and survival, as well as a controlled dietary intake, the SIV-infected rhesus monkey is an ideal model to examine the potential benefit of micronutrient supplementation. To this end we plan to: 1) document the course of micronutrient deficiency and weight loss in SIV-infected juvenile rhesus macaques compared to age matched uninfected control animals; and 2) conduct 3 interventions with micronutrients in SIV infected macaques, including a high supplementation with vitamins and trace minerals; single supplementation with vitamin B12 intramuscularly; and a single supplementation selenium. End points include time of death; body weight and lean body mass; serum micronutrients; viral load; CD4 cell count; and development of opportunistic infections. These studies will allow the evaluation of the efficacy of micronutrient supplements in the monkey SIV model without the confounding factors involved in a study in human HIV infection. In addition, the natural history of nutritional deficits and wasting would be defined in this model, which would provide a basis for further studies on nutritional interventions.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR013843-03
Application #
6330639
Study Section
Special Emphasis Panel (ZRG5-AARR-6 (01))
Program Officer
Robinson, Jerry
Project Start
1998-12-01
Project End
2002-02-28
Budget Start
2000-12-01
Budget End
2002-02-28
Support Year
3
Fiscal Year
2001
Total Cost
$376,880
Indirect Cost
Name
Tufts University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Goldin, Barry R; Li, Wenjun; Mansfield, Keith et al. (2005) The effect of micronutrient supplementation on disease progression and death in simian immunodeficiency virus-infected juvenile male rhesus macaques. J Infect Dis 192:311-8
Freeman, Lisa M; Mansfield, Keith G; Goldin, Barry et al. (2004) Body-composition changes in the simian immunodeficiency virus-infected juvenile rhesus macaque. J Infect Dis 189:2010-5