Limited durability of viral control following treated acute HIV infection.
Limited durability of viral control following treated acute HIV infection.
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DOI：
10.1371/journal.pmed.0010036
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发表时间：
2004-11
期刊：
影响因子：
15.8
通讯作者：
Walker BD
中科院分区：
文献类型：
--
作者：
Kaufmann DE;Lichterfeld M;Altfeld M;Addo MM;Johnston MN;Lee PK;Wagner BS;Kalife ET;Strick D;Rosenberg ES;Walker BD
在急性人类免疫缺陷病毒（HIV）感染早期采用高效抗逆转录病毒疗法治疗，随后进行有监督的治疗中断（STI），这至少与病毒血症的短暂控制有关。然而，这种控制的持久性仍不明确。在此我们对一项单臂、开放标签研究进行纵向随访，该研究评估了在急性HIV - 1感染情况下治疗中断的影响。
14名患者在急性HIV - 1感染期间接受了治疗，随后遵循一项治疗中断方案，如果病毒载量超过每毫升血浆50,000个RNA拷贝或连续三周以上保持在每毫升5,000拷贝以上，则需要重新治疗。14名患者中有11名（79%）在一次、两次或三次治疗中断后，能够在至少90天内使病毒载量达到低于每毫升5,000个RNA拷贝。然而，在大多数个体中观察到病毒血症逐渐增加以及CD4 + T细胞计数下降。通过意向性治疗分析，14名患者中有8名（57%）、6名（43%）和3名（21%）分别实现了最长为180天、360天和720天的控制期，尽管HIV特异性CD4 +和CD8 + T细胞反应有所增强。治疗中断前HIV - 1特异性细胞免疫反应的强度并不能预测病毒血症控制的持续时间。由于样本量小且缺乏同期未治疗的对照组，尽管按照研究标准未能控制病毒血症，但无法评估可能的临床益处。
这些数据表明，尽管最初对病毒血症有控制作用，但在急性HIV - 1感染治疗后的患者中，很少能将病毒持久控制在每毫升血浆低于5,000个RNA拷贝。确定早期治疗是否能带来整体临床益处将需要一项更大规模的随机临床试验。这些数据可能与当前开发旨在延缓疾病进展而非预防感染的HIV - 1疫苗的努力相关，因为它们表明可能难以实现对低水平病毒血症的持久维持。
对14名在急性感染期间接受高效抗逆转录病毒疗法（HAART）随后进行有监督的治疗中断的患者的长期随访表明，大多数患者未能实现对病毒血症的持久控制。
Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection. Fourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria. These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve. Long-term follow-up of 14 patients on HAART during acute infection followed by supervised treatment interruptions shows that most failed to achieve lasting control of viremia.
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