Current use of statins reduces risk of HIV rebound on suppressive HAART.
Current use of statins reduces risk of HIV rebound on suppressive HAART.
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DOI：
10.1371/journal.pone.0172175
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Bedimo R
中科院分区：
文献类型：
--
作者：
Drechsler H;Ayers C;Cutrell J;Maalouf N;Tebas P;Bedimo R
尽管有令人信服的证据表明他汀类药物在体外具有抗HIV-1的活性，但在临床研究中尚未显示他汀类药物的病毒学效应。鉴于它们的等离子体半衰期短，这种影响可能是短暂的，只有在持续暴露时才会明显。我们研究了1995-2011年开始HAART治疗的所有HIV感染的美国退伍军人，他们有记录的HIV病毒载量（VL）为1000拷贝/mL，在HAART治疗中达到不可检测的VL，并且在13个月内随访VL≥1。我们将病毒学失败（VF）定义为第一次VL >1,000拷贝/mL或第一次连续2次VL >200拷贝/mL。我们建立了抗逆转录病毒药物（ARVs）、他汀类药物和其他心血管药物（cvm）的时间更新药物暴露模型，调查了当前使用情况（是/否）、最近使用情况（使用天数比例）和分类使用情况（曾经/从未）。我们使用多重调整和逆概率加权（IPW） Cox模型来探讨他汀类药物、CVM使用和VF之间的关系。符合入选标准的退役军人19,324人。中位随访13个月（IQR: 5-32个月）；63%的患者在中位时间9个月（IQR 4-21个月）后出现VF。近1/3的患者曾使用过他汀类药物，但在初始处方后的随访时间中，暴露时间仅占41%。未经调整，目前他汀类药物的使用与VF的风险比（HR）为0.60相关（CI: 0.56-0.65）。在人口统计学、HIV和HAART参数的多变量调整（MVA）后，这一结果仍然具有统计学意义[HR 0.81 (CI: 0.75-0.88), p<0.001]和IPW（截断<1%/>99%）HR: 0.83 (CI: 0.75-0.92), p<0.001]。其他cvm无独立关联。他汀类药物的使用与MVA后VF的相关性要弱得多：HR 0.94 （CI: 0.88-1.00, p = 0.04）。在单变量、多变量和反概率加权模型中，当前他汀类药物暴露与VF风险降低相关。我们的结果强调了时间更新的药物暴露模型对观察性研究的重要性。
Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure. We studied all HIV infected US-Veterans who started HAART 1995–2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF. 19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5–32 months); 63% experienced VF after a median time of 9 months (IQR 4–21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56–0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75–0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75–0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88–1.00, p = 0.04). Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.