Exploring an alternative explanation for the second phase of viral decay: infection of short-lived cells in a drug-limited compartment during HAART

Most HIV-infected patients who initiate combination antiretroviral therapy experience a viral load decline in several phases. These phases are characterized by different rates of viral load decay that decrease when transitioning from one phase to the next. There is no consensus as to the origin of these phases. One hypothesis put forward is that short- and long-lived infected cells are responsible for the first and second phases of decay, respectively. However, significant differences in drug concentrations are observed in monocytes from various tissues, suggesting the first two phases of decay in viral loads could instead be attributed to short-lived cells being differently exposed to drugs. Compared to a well-exposed compartment, new cell infection can be expected in a compartment with limited drug exposure, thus leading to a slower viral load decay with potential virologic failure and drug resistance. In the current study, the latter hypothesis was investigated using a model of viral...

大多数启动联合抗逆转录病毒治疗（combination antiretroviral therapy）的人类免疫缺陷病毒（HIV）感染患者，其病毒载量会经历多个阶段的下降。这些阶段的特征是病毒载量衰减速率不同，且从一个阶段过渡到下一个阶段时衰减速率会降低。目前对于这些阶段的成因尚未达成共识。一种假说认为，短寿命和长寿命受感染细胞分别是第一和第二衰减阶段的原因。然而，在来自不同组织的单核细胞（monocytes）中观察到药物浓度存在显著差异，这表明病毒载量的前两个衰减阶段可能反而归因于短寿命细胞暴露于药物的程度不同。与药物充分暴露的区域相比，药物暴露有限的区域可能会发生新的细胞感染，从而导致病毒载量衰减更慢，并可能出现病毒学失败和耐药性。在本研究中，使用病毒模型对后一种假说进行了研究……