Zoufaly A, Kiepe J G, Hertling S, Hüfner A, Degen O, Feldt T, Schmiedel S, Kurowski M, van Lunzen J
Department of Medicine 1/Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
HIV Med. 2014 Sep;15(8):449-57. doi: 10.1111/hiv.12134. Epub 2014 Feb 24.
Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips.
HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients.
Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/μL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46).
The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.
病毒载量波动被认为代表了残余HIV病毒血症稳态周围的随机生物学变异，且缺乏临床意义。我们旨在评估免疫激活与病毒载量波动发生之间的关联。
从我们的门诊队列中选取在接受至少180天完全抑制性高效抗逆转录病毒疗法（HAART）后出现病毒载量波动的HIV感染患者，根据完全病毒抑制（CVS）持续时间、年龄、性别和疾病控制与预防中心（CDC）分期，与未出现病毒载量波动的患者进行匹配。将CD3(+)、CD3(+) CD4(+)、CD3(+) CD8(+)、CD3(+) HLA-DR(+)、CD4(+) CD45RA(+)、CD16(+) CD56(+) CD3(-)和CD19(+)细胞的频率，以及C反应蛋白（CRP）水平和临床参数纳入条件逻辑回归模型。通过测量57例患者样本中规定的非核苷类逆转录酶抑制剂（NNRTI）或蛋白酶抑制剂（PI）的血浆水平来评估对HAART的依从性。
82例出现病毒载量波动的患者与同一队列中的82例对照进行了匹配。平均年龄为47.2岁[标准差（SD）12.1岁]，80.5%的患者为男性，42.7%的患者患有CDC C期疾病。病毒载量波动发生在CVS中位数为14个月[四分位间距（IQR）8 - 34个月]之后。在逻辑回归中，活化的CD3(+) HLA-DR(+)淋巴细胞[比值比（OR）每100个细胞/μL为1.25；95%置信区间（CI）1.02 - 1.54；P = 0.03]与病毒载量波动显著相关，且HAART治疗时间较长与病毒载量波动存在关联趋势（OR每年1.31；95% CI 0.96 - 1.78；P = 0.09）。未发现亚治疗药物水平的组间差异（P = 0.46）。
抑制性HAART治疗后病毒载量波动的发生与T细胞激活标志物升高有关。病毒载量波动可能识别出免疫激活较高且HIV疾病进展风险增加的患者亚组。
