Preventative cardiologyImpact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy*
Section snippets
Methods
We used data from a recently completed, phase 2, randomized trial that compared atazanavir with nelfinavir.3 Study AI 424-008 was a multinational, randomized, active-controlled, 3-arm study that was designed to evaluate and compare the safety, tolerability, and antiviral activity of the HIV protease inhibitor atazanavir at 2 different doses (400 or 600 mg/day) with those of nelfinavir (1,250 mg twice daily), each in combination with stavudine and lamivudine, over 48 weeks. Study drug was
Results
The baseline characteristics of patients enrolled in study AI 424-008 are presented in Table 1. At baseline, the median blood lipid levels were similar in the 2 treatment arms. After 32 weeks of triple therapy, changes in total cholesterol and low-density lipoprotein cholesterol among patients who received nelfinavir (+24% and +28%) were significantly greater (p <0.05) than among patients who received atazanavir (+4% and +1%). The percent change in triglycerides was also significantly different
Discussion
There is strong evidence that multidrug antiretroviral therapy, including the use of protease inhibitors, is associated with dyslipidemia.1, 2, 19, 20, 21 In a recently completed randomized trial of triple therapy that compared atazanavir with nelfinavir and described in this report, nelfinavir was associated with significant increases in triglycerides, total cholesterol, and low-density lipoprotein cholesterol.3 Patients who received atazanavir did not demonstrate any significant change in
References (30)
- et al.
Severe premature coronary artery disease with protease inhibitors
Lancet
(1998) - et al.
Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor–associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study
Lancet
(1999) - et al.
Vascular complications associated with use of HIV protease inhibitors
Lancet
(1998) - et al.
Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results
AIDS
(2003) - et al.
Estimating the benefits of modifying risk factors of cardiovascular diseaseA comparison of primary vs secondary prevention
Arch Intern Med
(1998) - et al.
An updated coronary risk profileA statement for health professionals
Circulation
(1991) - et al.
Lipoprotein-cholesterol distributions in selected North American populations: the Lipid Research Clinics Program Prevalence Study
Circulation
(1980) The Lipid Research Clinics Coronary Primary Prevention Trial resultsII. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering
JAMA
(1984)- et al.
Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study
JAMA
(1988) - et al.
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
N Engl J Med
(1990)
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Lancet
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels
N Engl J Med
Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia
N Engl J Med
Prevention of stroke antihypertensive drug treatment in older persons with isolated systolic hypertension
JAMA
Primary prevention with metoprolol in patients with hypertension
JAMA
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This study was supported by Bristol-Meyers Squibb Company, Wallingford, Connecticut.*
- *
The sponsor provided the principal investigator with the results of study AI 424-008 before the study's subsequent publication but did not participate in the data analysis presented in this report. A draft of the manuscript was submitted to the sponsor before submission with the understanding that the final manuscript remained under the complete control of the principal investigator.