Cardiometabolic risk factors among HIV patients on antiretroviral therapy

Kiage et al. Lipids in Health and Disease 2013, 12:50 http://www.lipidworld.com/content/12/1/50 RESEARCH Open Access Cardiometabolic risk factors among HIV patients on antiretroviral therapy James N Kiage1, Douglas C Heimburger1,4,5, Christopher K Nyirenda6, Melissa F Wellons2, Shashwatee Bagchi7, Benjamin H Chi8,9, John R Koethe3,8, Donna K Arnett10 and Edmond K Kabagambe1,10* Abstract Background: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. Results: From baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. Conclusion: Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen. Keywords: Lipids, cART, Cardiometabolic risk, Zambia Introduction HIV/AIDS patients have increased risk for adverse cardiovascular outcomes and diabetes [1-3]. Both the HIV infection and combination antiretroviral therapy (cART) are independently associated with increased cardiometabolic risk [4,5]. Studies, mainly from developed countries, have shown that certain cART regimens, particularly combinations containing protease inhibitors, are associated with increased serum triglycerides (TG), low-density lipoprotein cholesterol (LDL-c) and total cholesterol (TC) as well as insulin resistance, while little or no effect is seen on high* Correspondence: 1 Department of Medicine, Division of Epidemiology, Vanderbilt University, Nashville, TN 37203, USA 10 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA Full list of author information is available at the end of the article density lipoprotein cholesterol (HDL-c) [6-8]. This constellation of dyslipidemia, especially elevation of TC:HDL-c ratio, and insulin resistance is thought to enhance the process of atherosclerosis, thus partly explaining the link between cART and adverse cardiometabolic outcomes [9-11]. Although protease inhibitor sparing combinations have also been associated with similar lipid changes, they result in substantial HDL-c elevation and relatively lower elevations of TG and LDL-c [6]. This lipid profile, especially the elevation of HDL-c, is thought to be beneficial to cardiovascular health [6,11,12]. However, few studies have explored the association between cART and cardiovascular health within resourceconstrained settings where the majority of HIV/AIDS cases reside and where the prevalence of traditional cardiovascular risk factors, such as excess adiposity, a high fat diet, and smoking, may be lower [13-15]. Findings © 2013 Kiage et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Kiage et al. Lipids in Health and Disease 2013, 12:50 http://www.lipidworld.com/content/12/1/50 from developed countries may not hold in resource-poor settings due to factors that could potentially modify cardiovascular risk e.g., age of the population, differences in HIV subtypes, diet, lifestyle as well as genetics [14]. The ongoing expansion of the cART programs within resource-limited settings highlights the need to quantify cardiometabolic risk associated with different antiretroviral combinations in these settings [15,16]. Using serum lipids and markers of insulin resistance as cardiometabolic risk markers, we investigated changes in cardiometabolic risk following cART among treatmentnaïve HIV positive patients initiating therapy in Zambia. We also tested whether the changes in cardiometabolic risk markers varied by cART regimen. Methods Ethics statement The study was approved by the Institutional Review Board of the University of Alabama at Birmingham (UAB) and the Research Ethics Committee of the University of Zambia. All participants gave written informed consent. Study design and population The current analysis is based on data from the Diet, Genetic Polymorphisms in Lipid-Metabolizing Enzyme genes, and Antiretroviral Therapy-Related Dyslipidemia (DGPLEAD) study which was carried out in Chawama Clinic, Lusaka, Zambia. The study has been described elsewhere [17]. In brief, 210 cART-naïve HIV/AIDS patients were recruited between January and December 2007. Men and women aged 16.5-60 years who were eligible to begin cART according to the Zambia HIV national guidelines and had BMI ≥16 kg/m2 and CD4+ lymphocyte count ≥50 cells/μL were invited into the study. All participants who gave consent were enrolled. The aforementioned BMI and CD4+ criteria were used because another study in the same clinic simultaneously recruited participants with BMI and CD4+ levels below these thresholds [18]. cART was prescribed according to the Zambian national guidelines at the time. Regimens comprised 2 nucleoside reverse transcriptase inhibitors (NRTI), for example zidovudine [AZT] and lamivudine [3TC] or stavudine [D4T] and lamivudine [3TC], and a non-nucleoside reverse transcriptase inhibitor, for example efavirenz [EFV] or nevirapine [NVP]. Tenofovir [TDF] and emtricitabine [FTC] were introduced into the first-line NRTI backbone in July 2007, while the study was underway [19]. No protease inhibitors were included in the regimens. Data collection At the initial visit, data on smoking, physical activity and alcohol intake were collected using standardized Page 2 of 9 questionnaires. In addition, dietary intake was assessed using 24-hour dietary recalls; the Nutrition Data System for Research software was used to determine dietary nutrient content. Zambian foods not in the dat (...truncated)