The independent effect of drug resistance on T cell activation in HIV infection
The independent effect of drug resistance on T cell activation in HIV infection
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DOI：
10.1097/01.aids.0000216369.30948.18
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发表时间：
2006-03-21
期刊：
影响因子：
3.8
通讯作者：
Martin, JN
中科院分区：
文献类型：
--
作者：
Hunt, PW;Deeks, SG;Martin, JN
目的：抗逆转录病毒治疗的耐药HIV患者与未治疗的患者相比，其CD4细胞计数下降的速度较慢，与病毒血症的程度无关。由于免疫激活独立地预测疾病的进展，我们假设抗药性病毒血症患者的免疫激活程度低于野生型病毒血症患者，与血浆HIV RNA水平无关，这些差异不能用蛋白酶抑制剂的直接药效来解释。方法：在调整血浆HIV RNA水平和其他与T细胞激活相关的因素后，比较未治疗的野生型病毒血症患者和抗逆转录病毒治疗患者的(CD38/HLA-DR)T细胞激活百分比。结果：21名未接受治疗的野生型病毒血症患者和70名抗逆转录病毒治疗患者的抗药性病毒血症患者接受了评估。与未经治疗的参与者相比，那些患有抗药性病毒血症的患者在调整了血浆HIVRNA水平等因素后，活化的CD_4(P=0.051)和CD_8(P=0.012)T细胞减少了29%。13例耐药病毒血症患者在继续服用其他抗逆转录病毒药物的同时，T细胞活化没有早期改变的证据，但T细胞活化显著增加，蛋白中完全或部分出现野生型序列。结论：抗逆转录病毒治疗的耐药病毒血症患者T细胞活化程度低于未治疗患者，与血浆HIV RNA水平无关。耐药变异体导致T细胞活化的能力降低可能是耐药病毒血症患者中CD4细胞数量下降较慢的原因之一。(C)2006年，Lippincott Williams&Wilkins。
Objective: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors.Methods: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and anti retroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications.Results: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 Subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease.Conclusions: Anti retroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia. (C) 2006 Lippincott Williams & Wilkins.