HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression
HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression
复制标题
DOI：
10.1073/pnas.96.26.15109
复制
发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Lane, HC
中科院分区：
文献类型：
--
作者：
Davey, RT;Bhat, N;Lane, HC
确定hiv感染患者停止抗逆转录病毒治疗的免疫学和病毒学后果对于制定HIV-1感染患者的长期治疗策略具有重要意义。我们设计了一项试验，在中断高活性抗逆转录病毒治疗（HAART）后，对抗逆转录病毒药物长期维持病毒抑制的患者进行这些参数的表征。18例CD4(+) T细胞计数大于或等于350个细胞/ μ l，病毒载量低于检测限大于或等于1年的患者在HAART治疗期间被前瞻性纳入一项停止HAART治疗的试验。这些患者中有12人先前接受过IL-2治疗，并且静止的潜伏感染CD4细胞的频率很低。在所有18例独立于既往IL-2治疗的患者中，病毒载量复发至bb50拷贝/ml，最常见的是在HAART停止后2-3周开始。平均复发率常数为0.45 (0.20 log(10) copies) day(-1)，与药物恢复后的平均病毒清除率常数0.35 (0.15 log(10) copies) day（-1）非常相似（P = 0.28）， 1例患者复发延迟至第7周。除1名患者外，所有患者的复发负担均达到50 000 RNA拷贝/ml。BrdUrd体外标记显示，HAART停药后CD4和CD8细胞周转增加，并与病毒载量相关，而淋巴细胞周转在重新开始药物治疗后下降。停止抑制药物治疗的患者病毒学复发迅速发生，即使在休眠、潜伏感染的CD4(+) T细胞池明显减少的患者中也是如此。
Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection, We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4(+) T cell counts greater than or equal to 350 cells/mu l and viral load below the limits of detection for greater than or equal to 1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies/ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2-3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log(10) copies) day(-1), which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log(10) copies) day(-1) (P = 0.28), One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to > 5,000 RNA copies/ml, Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4(+) T cells.