Mechanisms of Lipid Elevations Associated With the Treatment of Patients With HIV Infection

Peter J. Piliero, MD

In This Article

Abstract and Introduction

Objective: Dyslipidemia and other metabolic abnormalities, which are associated with the use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection, are of concern to patients and healthcare providers. The objective of this review is to present the current understanding of the dyslipidemia associated with the protease inhibitor (PI)-component of HAART: its possible origin, potential consequences, and management techniques.
Data sources, study selection: Peer-reviewed, published literature was identified via MEDLINE. Other sources included abstracts from recent HIV-related conferences that presented data pertinent to the topic. Studies were selected based on their impact on our understanding of HIV infection and its treatment.
Data extraction, synthesis: Relevant portions of the publications considered were compiled and conclusions were drawn based on the clinical experience of the author.
Conclusion: Dyslipidemia associated with current PIs should be a serious consideration when initiating long-term treatment of HIV infection. Current management techniques that include lipid-lowering agents may be improved and streamlined by incorporating a lipid-friendly PI into HAART.

Since 1995, morbidity and mortality in patients with advanced HIV infection have declined significantly,[1] largely because of the availability of more potent antiretroviral (ARV) therapies. Introduced in late 1995, protease inhibitors (PIs) have become integral components of highly active antiretroviral therapy (HAART) regimens.[2,3] PI-containing HAART regimens have produced dramatic declines in HIV viral loads and sustained increases in CD4 lymphocyte counts, both factors associated with delayed disease progression and onset of AIDS-associated events.[4,5,6,7] The achievement of longer life spans with HAART has transformed HIV from a progressive infection that leads to death to an incurable but chronic disease that may increase patients' risk of morbidity and mortality from the consequences of hypertension and dyslipidemia.

PIs have been most strongly linked to the development of lipodystrophy and dyslipidemia ( Table 1 ), although nevirapine, efavirenz, and stavudine have also been shown to cause dyslipidemia. In the general population, hypercholesterolemia and hypertriglyceridemia are both independent risk factors for coronary heart disease (CHD) and associated acute coronary syndromes. The Multiple Risk Factor Intervention Trial (MRFIT),[8] which screened more than 350,000 middle-aged men, showed a continuous, strong, and graded relationship between serum total cholesterol (TC) levels and CHD-related death that was independent of blood pressure and smoking history. The Copenhagen Male Study, carried out in 2906 middle-aged and elderly men, demonstrated elevated fasting triglyceride (TG) levels as a strong and independent risk factor for CHD.[9] Intervention studies support the correlation between elevated lipid levels and the development of CHD and show that pharmacologic strategies aimed at lowering low-density lipoprotein (LDL) cholesterol effectively reduce major coronary events and mortality.[10,11,12,13,14,15] In the HIV-infected patient whose disease is otherwise well controlled, development of hypercholesterolemia and hypertriglyceridemia have health implications similar to, if not greater than, the presence of these same lipid abnormalities in the general population.[16] Dyslipidemia adds a new and previously unanticipated health risk to the use of ARV therapy.