Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells.
Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells.
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DOI：
10.1186/s13287-022-02775-6
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发表时间：
2022-03-07
影响因子：
7.5
通讯作者：
Sen S
中科院分区：
文献类型：
--
作者：
Elzarki AF;Nandula SR;Awal H;Simon GL;Sen S
确定整合酶抑制剂（INSTI）与非基于ini的方案（如基于非核苷逆转录酶抑制剂（NNRTIs）的方案）对无明显CVD或糖尿病史、CD4:CD8计数正常的HIV+患者心血管疾病（CVD）风险的影响。对于心血管疾病风险评估，我们主要使用造血CD34+祖细胞作为生物标志物。19名男性受试者，年龄32-61岁，BMI 21.0-36.0。这是一个单时间点，横断面，观察性研究。受试者被分为两组（13名受试者采用以insti为基础的方案，6名受试者采用以NNRTI（非insti）为基础的方案），均服用稳定剂量的HAART。药物治疗方案是一种NRTI（通常是替诺福韦-恩曲他滨）加一种INSTI或NNRTI的组合。我们的结局指标集中在心血管和内皮细胞功能以及全身性炎症。我们的主要结局指标是外周血源性造血祖细胞数量（CD34和CD133阳性）、CD34+细胞功能和基因表达研究。我们的次要结果是动脉硬度测量和基于血清的炎症标志物。流式细胞术发现，与NNRTI组相比，INSTI组的CD133+祖细胞百分比显著增加（p = 0.004），双祖细胞标记阳性CD133+/CD34+祖细胞群也明显增加。与NNRTI组相比，抗氧化基因过氧化氢酶的mRNA基因表达与炎症标志物il - 6的基因表达呈下降趋势（p = 0.06）。血浆IL-6和CRP水平在两组间无明显变化。中性粒细胞-淋巴细胞比率（NLR）是炎症的重要标志，在INSTI组被注意到较低。与NNRTI组相比，INSTI组的平均空腹血糖水平也较低（p = 0.03）。有趣的是，与NNRTI组相比，INSTI组的尿微量白蛋白水平更高（p = 0.08），而INSTI组的eGFR水平明显较低（p = 0.002）。动脉硬度测量在两组之间没有统计学上的显著差异。我们得出结论，与基于nnrti的HAART方案相比，INSTI方案可能提供更好的心血管疾病风险状况；然而，在INSTI组中，蛋白尿增加和eGFR降低值得关注。由于规模小，在改变临床实践之前，这些结果还需要在其他研究中进行复制。临床试验注册https://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1。ClinicalTrials.gov标识符：NCT03782142。
To determine the effects of integrase inhibitor (INSTI) in comparison with non-INSTI-based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker. Nineteen male subjects, ages 32–61 years with BMI 21.0–36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI-based regimen with 13 subjects or NNRTI (non-INSTI)-based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir–emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood-derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation. A significant increase in percentage number of progenitor cells, CD133+ cells (p = 0.004), was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population being observed in INSTI group as compared to NNRTI group, by flow cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend toward a decrease in gene expression of inflammatory marker IL6 (p = 0.06) being observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil–Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p = 0.03). Interestingly, urine microalbumin levels were higher in the INSTI group compared to NNRTI group (p = 0.08), while eGFR levels were significantly lower in the INSTI group (p = 0.002). The arterial stiffness measures did not show statistically significant differences between the two groups. We conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI-based HAART regimen; however, the increased albuminuria along with lower eGFR, noted in INSTI group, is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT03782142.
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影响因子：
9.3
作者：
Nandula SR;Kundu N;Awal HB;Brichacek B;Fakhri M;Aimalla N;Elzarki A;Amdur RL;Sen S
通讯作者：
Sen S
DOI：
10.1016/s2352-3018(21)00274-5
发表时间：
2022-01
期刊：
The lancet. HIV
影响因子：
--
作者：
Ward Z;Stone J;Bishop C;Ivakin V;Eritsyan K;Deryabina A;Low A;Cepeda J;Kelly SL;Heimer R;Cook R;Altice FL;Litz T;Terlikbayeva A;El-Bassel N;Havarkov D;Fisenka A;Boshnakova A;Klepikov A;Saliuk T;Deshko T;Vickerman P
通讯作者：
Vickerman P
影响因子：
37.8
作者：
Feinstein MJ;Hsue PY;Benjamin LA;Bloomfield GS;Currier JS;Freiberg MS;Grinspoon SK;Levin J;Longenecker CT;Post WS
通讯作者：
Post WS
影响因子：
4.3
作者：
Blassel L;Tostevin A;Villabona-Arenas CJ;Peeters M;Hué S;Gascuel O;UK HIV Drug Resistance Database
通讯作者：
UK HIV Drug Resistance Database
影响因子：
2.1
作者：
Khiyami, Anamil M.;Dore, Fiona J.;Sen, Sabyasachi
通讯作者：
Sen, Sabyasachi