Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.
Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.
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DOI：
10.1111/hiv.12128
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发表时间：
2014-08
期刊：
影响因子：
3
通讯作者：
Currier JS
中科院分区：
文献类型：
--
作者：
Lake JE;McComsey GA;Hulgan T;Wanke CA;Mangili A;Walmsley SL;Stramotas SA;Tracy R;Currier JS
可溶性CD 14（sCD 14）是一种单核细胞活化标志物，与HIV死亡率增加相关。我们评估了从PI或NNRTI转换为雷特格韦（RAL）的病毒学抑制的HIV感染女性中sCD 14和其他炎症生物标志物的48周变化。中心性肥胖和HIV-1 RNA <50拷贝/mL的HIV感染女性继续其保留胸腺嘧啶的NRTI骨架，并在第0周（立即）或第24周（延迟）随机转换为开放标签RAL。在探索性分析中，对储存的空腹血浆测量炎症生物标志物。37例可评价受试者中78%为非白人，中位年龄43岁，BMI 32 kg/m2，CD 4 + T细胞计数558个细胞/µL。基线时，两组间的生物标志物值相似。24周后，转换为RAL的受试者中位sCD 14显著下降（−21%（p<0.001）vs. PI/NNRTI −5%（p=0.49），两组之间p<0.01）。48周后，立即转换的受试者保持了这种下降，延迟转换的受试者在转换为RAL后经历了类似的下降（-10%，组内p<0.01）。立即转换受试者的TNF-α也出现初始升高，但在48周后未维持，在延迟转换受试者中也未观察到。在调整多次测试后，只有sCD 14的下降仍然显著。在这项中心性肥胖女性的随机试验中，从PI或NNRTI转换为RAL与sCD 14的统计学显著性下降相关。需要进一步研究以确定整合酶抑制剂与PI和/或NNRTI相比是否改善了单核细胞活化特征，以及抗逆转录病毒药物之间的测量差异是否转化为可证实的临床获益。
Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from PI or NNRTI. HIV-infected women with central adiposity and HIV-1 RNA <50 copies/mL continued their thymidine-sparing NRTI backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. Thirty-seven evaluable subjects were 78% non-White and had median age 43 years, BMI 32 kg/m2 and CD4+ T cell count 558 cells/µL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL (−21% (p<0.001) vs. PI/NNRTI −5% (p=0.49), between group p<0.01). After 48 weeks, immediate switch subjects maintained this decline and delayed switch subjects experienced a similar decline following switch to RAL (−10%, within-group p<0.01). Immediate switch subjects also experienced an initial increase in TNF-α that was neither maintained after 48 weeks nor seen in delayed switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. In this randomized trial of women with central adiposity, switch to RAL from PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared to PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.
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