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The Body PRO Covers: The 10th Conference on Retroviruses and Opportunistic Infections

Contribution of HAART to Cardiovascualr Disease

February 13, 2003

  • Carotid Intima-Media Thickness in HIV-Infected and Uninfected Adults: ACTG 5078 (Oral 131)
    Authored by J. Currier, M. Kendall, K. Henry, F. Torriani, S. Storey, C. Shikuma, K. Mickelberg, B. Alston, M. Basar, R. Zackin, H. Hodis
    View the original abstract


On behalf of the AIDS Clinical Trials Group (ACTG) 5078 team, Dr. Judith Currier, UCLA presented the baseline results of the trial evaluating "Carotid Artery Intima Thickness (IMT) in HIV-Infected and Uninfected Adults." Unlike other trials we have seen, the ACTG 5078 team carefully designed a study limiting the high-risk confounding factors and having matched HIV-seronegative controls to really focus on the contribution of HIV and its therapies.

Carotid IMT has been shown to be predictive of clinical cardiac events in individuals with and without cardiac symptoms. All seven sites were trained by a standard protocol, performed in duplicate and sent to a central reader at the Cleveland Clinic. All subjects were evaluated at baseline and at weeks 24, 48, 72 and 96. Each site enrolled a triad at a time consisting of one HIV infected individual on a protease inhibitor (PI) for at least two years, one HIV-infected individual not on a PI, and one HIV-seronegative control. All three subjects were matched for age within five years, race/ethnicity, sex, blood pressure status, smoking status and menopausal status for women. Subjects with high-risk coronary heart disease (CHD) risk factors such as diabetes, history of CHD either in the subject or a first-degree relative and uncontrolled hypertension were excluded from the study to limit the number of confounding factors.

A total of 45 triads were enrolled and one subject in the PI group of one triad discontinued prematurely. The median duration of PI use was 216 weeks. Each of the triads was well matched and the HIV groups were equally matched for CD4 and HIV viral load. The median CD4 was 530 in the PI group and 482 in the no-PI group. The nadir CD4 count was unavailable as was duration of HIV seropositivity. The cohort was predominantly male (90 percent) and white (76 percent) with a median age of 42 years and 56 percent non-smokers. All subjects were normotensive.

The ACTG 5078 team defined smokers as per the guidelines for the American Cancer Society, which are used for most cardiology studies conducted within the U.S.A. The median value of the labs were similar between the groups except for triglycerides (TG) and total cholesterol (TC) which were slightly higher in the PI group at 219 and 192 mg/dL respectively compared with 142, 107 mg/dL TG and 179, 187 mg/dL TC in the no PI and uninfected groups. There was also an increased weight-to-hip ratio among the PI group compared with the other two, however, there was no difference in body mass index or waist circumference.

The 5078 team reported that there was no significant difference in the measurements of the carotid IMT among the three groups. When one controls for the known CHD risk factors, the PI group did not have increased carotid IMT measurements compared with the no-PI or HIV-seronegative matched controls. Factors associated with an increased carotid IMT were low HDL, elevated TG (more pronounced when HDL is low), older age and increased body mass index (BMI). This by itself is very interesting as low HDL is associated with HIV infection and was among the first lipid abnormalities described prior to the introduction of HAART.

HAART, particularly ritonavir (RTV, Norvir)-containing regimens, has been implicated as a cause of hypertriglyceridemia. Although the 5078 team did not find a significant difference among the groups now, it may be too early to detect any differences. CHD may take decades to develop and it will be critical to follow this extremely well matched cohort for years, in fact longer than the team has initially planned. Although one can argue that this group is a low-risk group for CHD to start with, it is the most "pure" group currently being evaluated to diminish the contribution of the traditional risk factors and really be able to address the impact of HIV and its therapies long term. Let's hope they can get funding to follow this group for at least ten years!


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This article was provided by TheBodyPRO.com. It is a part of the publication The 10th Conference on Retroviruses and Opportunistic Infections.
 



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