HIV Molecular Research Group, School of Medicine, University College Dublin.
Cardiovascular Biology Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
AIDS. 2018 Apr 24;32(7):861-866. doi: 10.1097/QAD.0000000000001783.
Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC.
In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models.
Of 312 randomized participants, 310 were included in the analysis. Mean (SD) age 46.4 (9.3) years, 262 (85%) men and 201 (65%) white. At baseline, there was no significant between-group difference in sGPVI [tenofovir disoproxil fumarate/emtricitabine 3.75 (0.25) versus ABC/3TC 3.61 (0.22) ng/ml, P = 0.69]. Greater increases in sGPVI from baseline to week 48 occurred in those switched from ABC/3TC (effect size +0.57 ng/ml; 95% confidence interval, 0.2-0.94; P = 0.003). There was no significant baseline difference or change overtime in soluble P-selectin, soluble CD40 ligand or von Willebrand factor between groups.
The significant increases in sGPVI that occur with a switch from ABC/3TC are suggestive of changes in platelet function centred on platelet/collagen interactions and potentially represent an underlying mechanism to explain increased risk of myocardial infarction with ABC.
血小板功能改变被认为是导致接受核苷逆转录酶抑制剂阿巴卡韦（ABC）治疗的 HIV 感染者心肌梗死风险增加的潜在机制。本研究旨在观察 HIV 感染者从 ABC 转换治疗后血小板生物标志物的变化。
在一项前瞻性、48 周的研究中，对病毒抑制的 HIV-1 阳性受试者进行随机分组，一组继续使用 ABC/拉米夫定（ABC/3TC），另一组转换为替诺福韦酯/恩曲他滨，我们检测了不同时间点采集的血浆中可溶性糖蛋白 VI（sGPVI）、可溶性 P-选择素、可溶性 CD40 配体和血管性血友病因子，并使用混合效应模型评估差异。
312 名随机参与者中，310 名纳入分析。平均（标准差）年龄 46.4（9.3）岁，262 名（85%）男性和 201 名（65%）白人。基线时，替诺福韦酯/恩曲他滨组和 ABC/3TC 组的 sGPVI 无显著差异[替诺福韦酯/恩曲他滨组 3.75（0.25）ng/ml，ABC/3TC 组 3.61（0.22）ng/ml，P=0.69]。与 ABC/3TC 组相比，从基线到第 48 周 sGPVI 增加更显著（效应量+0.57ng/ml；95%置信区间，0.2-0.94；P=0.003）。两组间可溶性 P-选择素、可溶性 CD40 配体或血管性血友病因子在基线时无显著差异，且随时间无变化。
从 ABC/3TC 转换治疗后 sGPVI 的显著增加提示血小板功能改变，可能与血小板/胶原相互作用有关，这可能是 ABC 导致心肌梗死风险增加的潜在机制。
