A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses
A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses
复制标题
DOI：
10.3851/imp2350
复制
发表时间：
2012-01-01
影响因子：
1.2
通讯作者：
Alam, Rafeul
中科院分区：
文献类型：
--
作者：
Lichtenstein, Kenneth A.;Armon, Carl;Alam, Rafeul
背景：尽管HAART成功地抑制了HIV-1，但一些患者的免疫功能并没有得到很好的恢复。持续免疫激活引起的慢性炎症可能导致这种不良反应，导致HIV-1疾病的进展和一些非HIV-1合并症的发展。方法：我们对30名HIV-1感染患者进行了一项试验性研究，这些患者在长期稳定的HAART中进行了无法检测到的病毒载量和低的CD4(+)T细胞反应，以评估加入雷替格雷是否会对慢性炎症的生物标志物产生影响。对26例患者进行了为期1年的强化治疗随访。除了T细胞反应外，我们还观察了活化的CD4(+)和CD8(+)T细胞、几种促炎细胞因子和趋化因子以及记忆细胞对HIV-1相关肽的反应的变化。结果：尽管CD4(+)T细胞计数没有改善，但CD4(+)%、CD4(+)/CD8(+)比值和RANTES(受激活的正常T细胞表达和分泌的调节)的百分比变化显著增加，CD8(+)T细胞计数和CD8(+)%的百分比变化显著，活化的CD4(+)T细胞和几种促炎趋化因子和细胞因子明显减少。HIV-1特异性NEF、POL SET 1、GAG和env记忆T细胞的百分比变化也有所下降。结论：在免疫应答较差的HAART方案中，加入Raltegravir后，几种促炎生物标志物减少；RANTES水平和CD4(+)/CD8(+)T细胞比率上升。这些观察的临床相关性超出了本研究的范围。
Background: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities.Methods: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4(+) T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation. A total of 26 patients were followed for 1 year on the intensified regimen. In addition to T-cell responses, we evaluated changes in activated CD4(+) and CD8(+) T-cells, several pro-inflammatory cytokines and chemokines and memory cell responses to HIV-1-associated peptides.Results: Although there was no improvement in CD4(+) T-cell counts, the percentage change in CD4(+)%, CD4(+)/CD8(+) ratios and RANTES (regulated on activation normal T-cells expressed and secreted) increased significantly while the percentage change in CD8(+) T-cell counts and CD8(+)%, activated CD4(+) T-cells and several pro-inflammatory chemokines and cytokines decreased significantly. The percentage change in HIV-1-specific nef, pol set 1, gag and env memory T-cells also declined.Conclusions: The addition of raltegravir to a virologically suppressive HAART regimen in patients with poor immunological responses resulted in the reduction of several pro-inflammatory biomarkers; increases were seen in RANTES levels and CD4(+)/CD8(+) T-cell ratios. The clinical relevance of these observations is beyond the scope of this study.