Preventative cardiology
Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy*

https://doi.org/10.1016/j.amjcard.2004.11.004Get rights and content

We investigated the effect of dyslipidemia associated with highly active antiretroviral therapy on cardiovascular risk and life expectancy among patients who had the human immunodeficiency virus. Dyslipidemia estimates were based on results from a phase 2 randomized trial that compared lipid changes after 32 weeks of therapy with atazanavir with those with nelfinavir (each in combination with stavudine and lamivudine). The resultant increased coronary risk was estimated using Framingham risk equations, and change in life expectancy (after adjustment for mortality due to human immunodeficiency virus) was based on the cardiovascular life expectancy model, which is based on a published Markov's model. Levels of total cholesterol and low-density lipoprotein cholesterol increased significantly more among patients who used nelfinavir (+24% and +28%) than among those who used atazanavir (+4% and +1%). This dyslipidemia increased the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia was estimated to preserve life expectancy 0.15 to 1.53 additional years depending on a patient's age, gender, and other risk factors. There are increasing reports of dyslipidemia and cardiovascular events associated with highly active antiretroviral therapy. Significant increases in blood lipid levels observed with some protease inhibitors are associated with an increase in calculated 10-year coronary risk. Accordingly, minimizing dyslipidemia associated with highly active antiretroviral therapy may preserve life expectancy among adults who have the human immunodeficiency virus.

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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

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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.

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