ORIGINAL RESEARCH Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naı ¨ve cohort WM El-Sadr, 1 CM Mullin, 2 A Carr, 3 C Gibert, 4 C Rappoport, 5 F Visnegarwala, 6 C Grunfeld 7 and SS Raghavan 1 1 Harlem Hospital and Columbia University, New York, NY, 2 School of Public Health, University of Minnesota, Minneapolis, MN, 3 St Vincent’s Hospital, Sydney, Australia, 4 Veterans Affairs Medical Center and George Washington University Medical Center, Washington, DC, 5 University of California, San Francisco, CA, 6 Houston AIDS Research Team and Baylor College of Medicine, Houston, TX, and 7 San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Objectives With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. Methods Demographic information and fasting blood samples were collected from 419 antiretroviral-naı ¨ve HIV-1-infected patients. Results The average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/mL, the mean baseline log 10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. Conclusions Both HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied. Keywords: lipids, glucose, insulin, HIV infection, antiretroviral naive Received: 11 April 2004, accepted 28 October 2004 Introduction Since the early days of the HIV epidemic, the effects of HIV disease on serum lipids have been described. Studies Correspondence: Dr Wafaa El-Sadr, Harlem Hospital Center, Division of Infectious Diseases, Room 3101A, 506 Lenox Avenue, New York, NY 10037, USA. Tel: 212 9392936; fax: 212 9392968; e-mail: wme1@columbia.edu HIV Medicine (2005), 6, 114–121 r 2005 British HIV Association 114