. Reports of increased glucose triglyceride, and cholesterol levels in HIV-infected patients on protease inhibitors (PI) have prompter speculation that these agents have unique metabolic effects. Additionally, some HIV-infected patients have noted increased abdominal girth and buffalo humps that clinicians and patients attribute to the use of Pi's. In preliminary studies, we have observed significant increases in glucose, insulin, TG and total LDL cholesterol in a group of patients following initiation of therapy with a PI, whereas no such changes occurred in patients beginning therapy with lamivudine or maintaining constant regimen that did not include lamivudine or a PI. Because hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and central obesity are associated with increased risk of cardiovascular disease, these effects may impact on the long-term prognosis in patients whose life expectancies are extended due to effective viral suppression. As yet, these metabolic and body composition changes have not been systematically characterized, nor is it known if these changes represent one year syndrome or are unrelated findings. Therefore,, to evaluate the scope of and mechanisms underling these changes in carbohydrate and lipid metabolism and their relationship, if any, to changes in body composition, e propose to perform intensive metabolic ward studies in which we prospectively evaluate changes in glucose and lipid metabolism and body composition in separate cohorts of HIV-infected men and women before and after beginning Pi therapy. These studies are designed to: (1) test the hypothesis that PI's induce insulin resistance (as assessed by oral glucose tolerance test, hyperinsulinemic, euglycemic clamp, stable isotope studies of hepatic glucose production, gluconeogenesis and glycogenesis); 2) test the hypothesis that PI's produce an atherogenic lipid profile (plasma lipids and lipoprotein composition, intravenous fat tolerance test, stable isotope studies of whole body lipolysis, de novo hepatic lipogenesis, and cholesterolgenesis); and (3) to determine whether patients uniformly develop changes in regional fat distribution while on PI therapy and the relationship, if any, or changes in glucose and lipid metabolism to changes in body composition (dual-energy X-ray absorptiometry, computed tomography)> The role of glucoregulatory, adrenal, and gonadal hormones in mediating these effects will also be evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK054615-02
Application #
2906308
Study Section
Special Emphasis Panel (ZRG5-AARR-6 (01))
Program Officer
Smith, Philip F
Project Start
1998-09-30
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dusingize, Jean Claude; Hoover, Donald R; Shi, Qiuhu et al. (2015) Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women. AIDS Res Hum Retroviruses 31:723-30
Tumusiime, David K; Musabeyezu, Emmanuel; Mutimurah, Eugene et al. (2014) Over-reported peripheral neuropathy symptoms in a cohort of HIV infected and uninfected Rwandan women: the need for validated locally appropriate questionnaires. Afr Health Sci 14:460-7
Benning, Lorie; Golub, Elizabeth T; Anastos, Kathryn et al. (2014) Comparison of lower genital tract microbiota in HIV-infected and uninfected women from Rwanda and the US. PLoS One 9:e96844
Dusingize, Jean Claude; Hoover, Donald R; Shi, Qiuhu et al. (2013) Associations of HIV infection with insulin and glucose levels in antiretroviral-naive Rwandan women: a cross-sectional analysis. BMJ Open 3:e003879
Kemal, Kimdar S; Anastos, Kathryn; Weiser, Barbara et al. (2013) Molecular epidemiology of HIV type 1 subtypes in Rwanda. AIDS Res Hum Retroviruses 29:957-62
Gard, Tracy L; Hoover, Donald R; Shi, Qiuhu et al. (2013) The impact of HIV status, HIV disease progression, and post-traumatic stress symptoms on the health-related quality of life of Rwandan women genocide survivors. Qual Life Res 22:2073-84
Adedimeji, Adebola A; Hoover, Donald R; Shi, Qiuhu et al. (2012) Differences in the Nonuse of any Contraception and Use of Specific Contraceptive Methods in HIV Positive and HIV Negative Rwandan Women. AIDS Res Treat 2012:367604
Dusingize, Jean-Claude; Hoover, Donald R; Shi, Qiuhu et al. (2012) Association of serum albumin with markers of nutritional status among HIV-infected and uninfected Rwandan women. PLoS One 7:e35079
Wyatt, Christina M; Shi, Qiuhu; Novak, James E et al. (2011) Prevalence of kidney disease in HIV-infected and uninfected Rwandan women. PLoS One 6:e18352
Cohen, Mardge H; Shi, Qiuhu; Fabri, Mary et al. (2011) Improvement in posttraumatic stress disorder in postconflict Rwandan women. J Womens Health (Larchmt) 20:1325-32

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