Carotid Artery Thickness Is Associated With Chronic Use of Highly Active Antiretroviral Therapy in Patients Infected With Human Immunodeficiency Virus

A 3.0 Tesla Magnetic Resonance Imaging Study

TM LaBounty; WD Hardy; Z Fan; R Yumul; D Li; R Dharmakumar; A Hernandez Conte

Disclosures

HIV Medicine. 2016;17(7):516-523. 

In This Article

Discussion

This study found that HIV-infected individuals receiving HAART for > 3 years had increased carotid artery wall thickness on MRI compared with HIV-negative controls, despite similar cardiovascular risk factors. Furthermore, among these HIV-seropositive subjects, increased wall thickness was associated with lipoaccumulation, elevated Framingham risk score, longer duration of protease inhibitor therapy, and a time from HIV diagnosis of ≥ 10 years.

Several carotid artery ultrasound studies have reported an increase in carotid intimal medial thickness among subjects with HIV infection compared with controls,[11,13–15] while other studies have reported no significant differences between groups.[16,17]

These studies examined heterogeneous populations, and generally included both treated and untreated subjects. In comparison, this study examined patients with HIV infection on chronic HAART, as this represents a group of individuals more likely to survive to an older age and to have an increased risk of cardiovascular events. All of our HIV-infected subjects had undetectable viral loads and high rates of medication adherence, suggesting an optimal HAART response. We further examined a relatively young population without known cardiovascular disease but with a significant time from HIV diagnosis (mean 16.8 years) and duration of HAART therapy (mean 13.4 years), which would be expected to have a low rate of carotid atherosclerosis absent HIV infection and concomitant use of HAART. These findings suggest that, despite optimal medical management of HIV infection with contemporary HAART regimens, a relatively young cohort of individuals with HIV infection may remain at increased risk for subclinical carotid artery atherosclerosis.

This study identified a positive relationship between clinical lipodystrophy and carotid wall thickness in patients with HIV infection on chronic HAART, which may be related to metabolic alterations in this population.[27] While these results contrast with those of a prior study using ultrasound,[15] these discordant results may be explained by differences in the examined populations, imaging modality and measurement techniques. It is important to note that, in comparison to ultrasound measurement of the intima and media, MRI measurement includes the adventitial layer, which may result in larger measurements. Nevertheless, in comparison to B-mode ultrasound, which only images two opposing points of the wall, MRI permits cross-sectional imaging; this has been demonstrated to correlate highly with ultrasound but with lower variability, potentially reducing the required sample size for clinical studies.[18]

Prior studies that included individuals with untreated HIV infection have reported decreased arterial distensibility by carotid artery ultrasound.[14,15,28] In contrast, the present study observed no change in carotid distensibility using MRI. It is possible that changes in distensibility are obviated in patients with well-controlled HIV infection on chronic HAART or with no evidence of systolic hypertension, although future study may be needed to investigate this issue further.

Increased carotid artery wall thickness was associated with prolonged exposure to protease inhibitors, while no significant relationship was observed with the overall duration of HAART. This is consistent with prior studies using carotid ultrasound,[29] and reports of increased myocardial infarctions associated with exposure to protease inhibitors but not to other antiretroviral medication classes.[26] It is also possible that increased duration of protease inhibitor use may be related to a longer time from HIV diagnosis; a larger study would be needed to investigate this potential relationship.

Limitations of this study include its small size, and multivariable adjustments and comparisons between treatment regimens could not be adequately performed as a result. In addition, while observed differences in carotid artery wall thickness were statistically significant, the magnitude of these differences was small (as reported in ultrasound studies); additional study in larger populations is needed to confirm these results. Further, this study was limited to men, and future research in women may be warranted. In addition, men with HIV infection often have disproportionate rates of cardiovascular risk factors and substance abuse, and such variables may be incompletely accounted for in analyses comparing these patients with controls. Finally, lipodystrophy was diagnosed on physical examination by infectious disease physicians experienced in assessing the presence of lipodystrophy in patients with HIV infection, but was not quantitatively determined by imaging. Future studies should consider quantitative imaging measurement of lipodystrophy to validate these findings.

In conclusion, individuals with HIV infection receiving chronic HAART had increased carotid artery wall thickness on MRI as compared with a control group similar in terms of age, gender and cardiovascular risk factors. Furthermore, we demonstrated that the presence of lipoaccumulation and longer duration of exposure to protease inhibitors were associated with greater carotid wall thickness. Future studies are needed to determine whether increased carotid artery wall thickness is associated with an increased risk of stroke, and to determine the mechanism contributing to these findings.

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