HIV-positive individuals treated with a protease inhibitor are significantly more likely to develop lesions in their carotid arteries than HIV-positive patients treated with non-nucleoside analogues (NNRTIs), who are naïve to HAART (or who are taking dual nucleoside analogue treatment), according to a study published in the April 30th edition of AIDS.
The study investigators used Colour-Doppler ultrasound to assess the thickness of carotid vessels. Accumulations of cholesterol, called plaques, in the carotid arteries are a risk factor for vascular and cerebro-vascular disease (in particular stroke), and the study investigators recommend that HAART-treated patients have periodic assessment of the thickness of artery walls using ultrasound.
A separate study has found that HIV-positive individuals generally have an increased risk of hardening of the arteries, the common term for the process through which cholesterol accumulates in the arteries and becomes hardened over time due to deposits of calcium and other debris. The study, which was conducted in San Francisco, involved 148 HIV-positive individuals who had the thickness of their carotid arteries assessed using an ultrasound examination. Age, LDL cholesterol and smoking were all independent risk factors for atherosclerosis. The study was presented to the Tenth Conference on Retroviruses and Opportunistic Infections in 2003 and is published in the April 6th edition of Circulation.
A total of 293 HIV-positive individuals were included in the study published in AIDS. These patients were divided into three exclusive groups dependent on their HIV treatment history. Group I included 105 patients who had received a protease inhibitor. The median duration of HAART in these individuals was 26 months. Patients in group II had all received a HAART regimen including an NNRTI. The median duration of HAART in this group was 24 months. Group III included both patients who had received dual NRTI therapy and those who were naïve to antiretroviral treatment. For patients who had received dual NRTI treatment, the median duration of therapy was 23 months.
All 293 patients had a colour-Doppler ultrasound to detect plaque lesions in the carotid vessels and to measure the intima-media thickness (ITM) of arteries (an indicator of the hardening of the arteries) and the speed of blood flow.
Of the protease inhibitor-treated patients, 55 (52.4%) had plaque lesions present in their carotid vessels and 25 had increased IMT indicative of pathology. In group II, 19 patients (15.2%) had plaques detected, and ten had increased IMT. In group three, nine patients (14.3%) had plaque lesions present, including three with increased IMT.
No abnormalities in blood flow or speed were detected and no patient had any neurological symptoms indicative of stroke risk.
In further analysis, the investigators found that treatment with a protease inhibitor (p=0.0001) and elevated triglycerides (p=0.01) were both significantly associated with an increased risk of vascular damage. The investigators also found that protease inhibitors were associated with elevated cholesterol (p
The investigators also found that the odds ratio (OR) of developing carotid plaques increased with age, with a 1.09 increase in OR per year. Smoking, a well-recognised risk factor for vascular damage, was also found to be significant (OR 2.22). The investigators also found that individuals with a CD4 cell count between 200-500 cells/mm3 were more likely to have vascular damage than patients with either a CD4 cell count below 200 cells/mm3 or above 500 cells/mm3 (OR 2.45, p=0.001). However, the most significant predictor of carotid plaques was treatment with a protease inhibitor (P
“These data suggest that the risk of premature damage to the carotid wall in HIV-1 infected patients is complicated by factors such as cigarette smoking and age, but that PI-containing regimens appear to play a role,” the investigators conclude. The investigators recommend that patients receiving HAART have periodic assessments of their vascular health using ultrasound and that individuals with rapidly worsening vascular plaques should have their HAART regimens changed and receive protease-sparing therapy.
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Maggi P et al. Colour-Doppler ultrasoundography of carotid vessels in patients treated with antiretroviral therapy: a comparative study. AIDS 18: 1023-1028, 2004.
Hsue PY et al. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 109: 1603-1608, 2004.