This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies in patients with HIV have revealed that serum micronutrient levels are often below normal levels and may cause more rapid progression of HIV-related diseases. Other studies have documented the effects of antiretroviral treatments on changes in body composition, glucose metabolism and lipid metabolism. Intervention trails with micronutrients and single antiretrovirals are difficult to carry out in humans, both practically and ethically. Because the Simian Immunodeficiency Virus (SIV) produces an infection in macaques that is remarkable similar to that caused by HIV in humans, it provides an ideal model to examine the potential benefit of micronutrient supplementation and antiretroviral intervention on progression of SIV infection. In animals receiving antiretroviral therapy on low fat, high fiber chow, there were no significant changes in fasting triglycerides, HDL, LDL, total cholesterol or glucose. However, there was a statistically significant increase in insulin area-under-the curve (p=0.04) and a decrease in adiponectin (p=0.05) and changes in trunk fat approaching significance (p=0.08). A second group of juvenile animals was switched to a high fat, low fiber Western Diet (WD) after inoculation. Two months after switching to the WD, animals began six months of treatment with PMPA (tenofovir). Neither diet change nor introduction of viral control with PMPA produced any significant difference in glucose or insulin area under the curve by IVGTT. The high fat WD diet alone resulted in significant increases in LDL-cholesterol and total cholesterol. However, these lipids did not change further after treatment with PMPA, thus confirming that PMPA itself does not induce changes in lipids. Adult female macaques fed a WD not only displayed significant increases in LDL and total cholesterol, but also had significant decreases in HDL-cholesterol and significant increases in triglycerides, mirroring the lipid profile seen in HIV-infected individuals. Given these results, more studies will be conducted using individual antiretrovirals and diets to examine the effects on lipid metabolism and body composition.
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