Guidelines for the Evaluation and Management of Dyslipidemia in Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group

Abstract

Dyslipidemia is a common problem affecting HIV-infected patients receiving antiretroviral therapy. Since publication of preliminary guidelines in 2000 [1], numerous studies have addressed the risk of cardiovascular disease, the mechanisms of dyslipidemia, drug interactions, and the treatment of lipid disorders in HIV-infected patients. In addition, updated recommendations from the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) have been published [2] that materially affect the clinical approach to lipid disorders in the general population. A working group of clinical scientists, consisting of members of the Cardiovascular Subcommittee of the AIDS Clinical Trials Group, updated the preliminary recommendations to assist clinicians in the evaluation and treatment of lipid disorders among HIV-infected adults. Data regarding the prevalence and incidence of dyslipidemia and cardiovascular disease in HIV-infected patients, pharmacokinetic profiles for hypolipidemic agents, and treatment trials of dyslipidemia in HIV-infected patients were considered. Although the implications of dyslipidemia in this population are not fully known, preliminary data indicate increased cardiovascular morbidity among HIV-infected individuals, suggesting that measures to reduce cardiovascular risk should be provided. We recommend that HIV-infected adults undergo evaluation and treatment on the basis of NCEP ATP III guidelines for dyslipidemia, with particular attention to potential drug interactions with antiretroviral agents and maintenance of virologic control of HIV infection. When drugs become necessary, we recommend as initial therapy pravastatin or atorvastatin for elevated low-density lipoprotein cholesterol levels and gemfibrozil or fenofibrate when triglyceride concentrations exceed 500 mg/dL. Cardiovascular disease and stroke are by far the leading causes of death and morbidity in the United States [3]. As the prognosis for HIV-infected persons steadily improves, these individuals will incur an increased risk for other major causes of morbidity and mortality, independent of any specific HIV- or treatment-related issue. Cardiovascular disease occurs earlier and at a higher rate in certain populations, such as black persons, that increasingly overlap with the epidemiology of HIV infection. It is reasonable to anticipate that this problem will worsen in the midst of the epidemic of obesity and diabetes in the United States [4] and elsewhere [5], an epidemic that disproportionately affects Hispanic and non-Hispanic black persons [6]. The close relationship between HIV care providers and their patients affords a major opportunity for primary and secondary prevention of non-HIV-related conditions, such as cardiovascular disease. These recommendations will assist the HIV clinician's efforts to broaden the health benefits associated with ongoing clinical care for adults in the HIV clinic. A comprehensive approach for evaluation and treatment of dyslipidemia in HIV-infected adults receiving antiretroviral therapy is outlined in figure 1. For particular recommendations and statements, the strength of the supporting evidence and quality of the data are rated by use of an Infectious Diseases Society of America-United States Public Health Service grading system [7] (table 1). A rating of A–E indicates the strength of a recommendation, and the Roman numerals I–III indicate the quality of the supporting evidence. These ratings are presented in parentheses after specific recommendations. General approach to lipid disorders and cardiovascular risk in HIV-infected patients receiving HAART. See text for additional explanation. CHD, coronary heart disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Infectious Diseases Society of America-United States Public Health Service grading system for rating recommendations in clinical guidelines. Abnormalities of lipid metabolism in HIV-infected patients were described before the advent of HAART [8–13]. Increased serum triglyceride [8] and reduced total cholesterol [13] concentrations were associated with advanced HIV disease. Patients with AIDS have also had lower levels of high-density lipoprotein (HDL) cholesterol (HDL-C) and low-density lipoprotein (LDL) cholesterol (LDL-C), decreased triglyceride clearance, and a predominance of small, dense LDL particles, compared with controls [9, 11]. Therapy with zidovudine alone was associated with reduced cytokine activation and a decrease in serum triglyceride levels [14]. Protease inhibitors (PIs). Use of HIV PIs has been associated with hyperlipidemia that is more common and more severe than what was observed before the advent of HAART [1, 15–22]. Sixty-two (47%) of 133 PI recipients at one clinic [20] had lipid abnormalities that met the 1994 NCEP intervention criteria [23]. In the Swiss HIV Cohort, hypercholesterol