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

TitleA prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness.
Publication TypeJournal Article
Year of Publication2015
AuthorsStein JH, Ribaudo HJ, Hodis HN, Brown TT, Tran TTien T, Yan M, Brodell ELauer, Kelesidis T, McComsey GA, Dubé MP, Murphy RL, Currier JS
JournalAIDS
Volume29
Issue14
Pagination1775-83
Date Published2015 Sep 10
ISSN1473-5571
KeywordsAdult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Carotid Arteries, Carotid Artery Diseases, Carotid Intima-Media Thickness, Female, HIV Infections, HIV-1, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies
Abstract

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) μm/year] than DRV/r [12.9 (10.3, 15.5) μm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) μm/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.

DOI10.1097/QAD.0000000000000762
Alternate JournalAIDS
PubMed ID26372383
PubMed Central IDPMC4571277
Grant ListK24 AI056933 / AI / NIAID NIH HHS / United States
R01 HL095132 / HL / NHLBI NIH HHS / United States
S10 OD010569 / OD / NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States