Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type 1-infected persons treated with suppressive antiretroviral therapy for five years
Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type 1-infected persons treated with suppressive antiretroviral therapy for five years
复制标题
DOI：
10.1128/jvi.77.20.11212-11219.2003
复制
发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Wong, JK
中科院分区：
文献类型：
--
作者：
Havlir, DV;Strain, MC;Wong, JK
为了深入了解抗逆转录病毒治疗成功的人类免疫缺陷病毒（HIV）患者中残留病毒血症的动力学和来源，对14例接受茚地那韦和依法韦仑治疗5年后维持HIV RNA的患者进行了研究。第5年，8名患者的治疗方案中添加了阿巴卡韦。在最初9个月的治疗后，HIV RNA水平达到了一个平台（“残留病毒血症”），持续5年以上。残留病毒血症的水平在患者之间不同，范围为3.2至23 HIV RNA拷贝/ml。在包括基线HIV RNA、CD 4计数和患者年龄的回归模型中，基线HIV DNA是残留病毒血症的唯一显著治疗前预测因子。在5年后加入阿巴卡韦的5名可检测到病毒血症的患者中，有4名患者的HIV RNA水平迅速下降。感染细胞的估计半衰期为6.7天。在ELISpot测定中观察到活化的记忆细胞减少以及针对HIV Gag和p24抗原的γ干扰素产生减少，这与HIV复制减少一致。因此，在接受依法韦仑加茚地那韦治疗的患者中，残留病毒血症水平在9个月时建立，通过基线前病毒DNA预测，并保持恒定5年。即使经过多年的高度抑制性治疗，HIV RNA水平在添加阿巴卡韦后迅速下降，这表明生产性感染有助于残留的持续病毒血症，并可通过强化治疗加以抑制。
To provide insight into the dynamics and source of residual viremia in human immunodeficiency virus (HIV) patients successfully treated with antiretroviral therapy, 14 intensely monitored patients treated with indinavir and efavirenz sustaining HIV RNA at 5 years were studied. Abacavir was added to the regimen of eight patients at year 5. After the first 9 months of therapy, HIV RNA levels had reached a plateau ("residual viremia") that persisted for over 5 years. Levels of residual viremia differed among patients and ranged from 3.2 to 23 HIV RNA copies/ml. Baseline HIV DNA was the only significant pretreatment predictor of residual viremia in regression models including baseline HIV RNA, CD4 count, and patient age. In the four of five patients with detectable viremia who added abacavir to their regimen after 5 years, HIV RNA levels declined rapidly. The estimated half-life of infected cells was 6.7 days. Decrease in activated memory cells and a reduction in gamma interferon production to HIV Gag and p24 antigen in ELISpot assays were observed, consistent with a decrease in HIV replication. Thus, in patients treated with efavirenz plus indinavir, levels of residual viremia were established by 9 months, were predicted by baseline proviral DNA, and remained constant for 5 years. Even after years of highly suppressive therapy, HIV RNA levels declined rapidly after the addition of abacavir, suggesting that productive infection contributes to residual ongoing viremia and can be inhibited with therapy intensification.