A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

作者：Stein James H^*; Ribaudo Heather J; Hodis Howard N; Brown Todd T; Tran Thuy Tien T; Yan Mingzhu; Brodell Elizabeth Lauer; Kelesidis Theodore; McComsey Grace A; Dube Michael P; Murphy Robert L; Currier Judith S

来源：AIDS, 2015, 29(14): 1775-1783.

DOI：10.1097/QAD.0000000000000762

• antiretroviral therapy
• atherosclerosis
• cardiovascular disease
• carotid arteries
• HIV

Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years.
Design: Randomized clinical trial.
Setting: Multicenter (26 institutions).
Patients: ART-naive HIV-infected individuals (n=328) without known cardiovascular disease or diabetes mellitus.
Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).
Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression.
Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8)m/year] than DRV/r [12.9 (10.3, 15.5)m/year, P=0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2)m/year, P=0.15 vs. ATV/r; P=0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates.
Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.

• 出版日期2015-9-10
• 单位西北大学