Effect of IL-2 on the pool of latently infected, resting CD4+ T cells in HIV-1

尽管HAART成功地将相当比例的HIV感染者的血浆病毒血症降低到可检测水平以下，但在HAART治疗的个体中，静止CD4+ T细胞中HIV潜伏库的持续存在被认为是HIV感染长期控制的主要障碍。为了减少或消除接受HAART治疗的感染者体内潜伏的CD4+ T细胞，我们研究了白细胞介素-2在清除接受IL-2 + HAART治疗的患者体内潜伏的CD4+ T细胞中的可能作用。我们对接受间歇IL-2 +连续HAART治疗的HIV-1感染患者中潜伏感染的静止CD4+ T细胞池进行了非随机、横断面分析，与单独接受连续HAART治疗的患者进行了比较。IL-2联合HAART患者血液中CD4+ T细胞携带复制能力HIV的频率显著低于单独HAART患者（p=0.01）。在接受IL-2 + HAART治疗的14名患者中，有6名患者的标准共培养试验未发现复制能力HIV，而单独接受HAART治疗的12名患者的静息CD4+ T细胞中均携带感染性HIV。在接受IL-2 + HAART治疗的6例标准共培养阴性患者中，尽管培养了大量静息CD4+ T细胞，但仍有3例患者外周血CD4+ T细胞中无法分离到病毒。3例患者中2例进行了淋巴结活检，病毒未分离。这些结果表明，间歇给药IL-2和持续HAART可能导致携带复制能力HIV的静止CD4+ T细胞池的大量减少。——艾滋病毒;病毒水库;延迟;静息CD4+ T细胞；高效抗逆转录病毒治疗；白介素2。-人体实验对象

Despite the success of HAART in driving plasma viremia to below the levels of detectability in a substantial proportion of HIV-infected individuals, the persistence of a latent reservoir of HIV in resting CD4+ T cells in HAART-treated individuals is considered to be a major impediment to the long-term control of HIV infection. In our attempts to diminish or eliminate latently infected, resting CD4+ T cells in infected individuals receiving HAART, we investigated a possible role of interleukin-2 in purging of latent HIV in resting CD4+ T cells in patients receiving IL-2 plus HAART. We conducted a non-randomized, cross-sectional analysis of this pool of latently infected, resting CD4+ T cells in HIV-1 infected patients receiving intermittent IL-2 plus continuous HAART compared to those receiving continuous HAART alone. The frequency of resting CD4+ T cells carrying replication- competent HIV in the blood of patients receiving IL-2 plus HAART was significantly lower than that of patients receiving HAART alone (p=0.01). Replication-competent HIV was not demonstrated by standard co-culture assays in 6 of 14 patients receiving IL-2 plus HAART, whereas all 12 patients receiving HAART alone carried infectious HIV in their resting CD4+ T cells. Of the 6 standard co-culture-negative patients receiving IL-2 plus HAART, virus could not be isolated from the peripheral blood CD4+ T cells in 3 patients despite the fact that large numbers of resting CD4+ T cells were cultured. Lymph node biopsies were then performed in 2 of these 3 patients and virus could not be isolated. These results suggest that the intermittent administration of IL-2 together with continuous HAART may lead to a substantial reduction in the pool of resting CD4+ T cells that harbor replication-competent HIV. - HIV; viral reservoir; latency; resting CD4+ T cells; highly active antiretroviral therapy; interleukin-2. - Human Subjects