Klastrup Vibeke, Gunst Jesper Damsgaard, Søgaard Ole Schmeltz
Department of Clinical Medicine, Aarhus University, Denmark.
Department of Infectious Diseases, Aarhus University Hospital, Denmark.
J Virus Erad. 2025 Jun 27;11(3):100604. doi: 10.1016/j.jve.2025.100604. eCollection 2025 Sep.
Analytical treatment interruption (ATI) is crucial for assessing the efficacy of HIV-1 cure strategies. Recent cure studies have implemented more flexible ART restart criteria, permitting higher plasma viral loads (pVLs) for longer periods, which could potentially impair CD4 T cell recovery even following ART resumption.
We conducted a pooled analysis of six clinical HIV cure trials that included an ATI to evaluate the impact of magnitude and duration of plasma viremia during ATI on CD4 T cell dynamics.
Wilcoxon signed-rank or rank-sum test was used to analyze differences in CD4 T cell counts from 3 time points: 1) pre-ATI, 2) ART resumption, and 3) ART-induced viral re-suppression, with analyses stratified by peak pVL (≤10,000 or >10,000 copies/mL) or by duration of viremia (0-14, 15-28, or >28 days).
Among 114 participants, we found no change in CD4 T cell counts from pre-ATI to post-ATI (at viral re-suppression, = 0.80). We also found no impact of low (≤10,000 copies/mL) versus high (>10,000 copies/mL) peak viremia on CD4 T cell counts at the time of ART resumption or viral re-suppression ( = 0.48, = 0.88, respectively). Similarly, the change in CD4 T cell count from pre-ATI to viral re-suppression did not differ significantly between individuals with viremia lasting 0-14 days versus those with >28 days.
In our pooled analysis, high peak rebound pVLs and longer duration of viremia did not impair CD4 T cell recovery following the resumption of ART, supporting the safety of more flexible ATIs in HIV-1 cure trials.
分析性治疗中断（ATI）对于评估HIV-1治愈策略的疗效至关重要。近期的治愈研究采用了更灵活的抗逆转录病毒治疗（ART）重启标准，允许更高的血浆病毒载量（pVL）持续更长时间，这可能会损害CD4 T细胞的恢复，即使在ART恢复之后。
我们对六项包含ATI的临床HIV治愈试验进行了汇总分析，以评估ATI期间血浆病毒血症的程度和持续时间对CD4 T细胞动态的影响。
采用Wilcoxon符号秩和检验或秩和检验分析三个时间点的CD4 T细胞计数差异：1）ATI前，2）ART恢复时，3）ART诱导的病毒再抑制时，分析按峰值pVL（≤10,000或>10,000拷贝/毫升）或病毒血症持续时间（0-14、15-28或>28天）分层。
在114名参与者中，我们发现从ATI前到ATI后（病毒再抑制时）CD4 T细胞计数没有变化（P = 0.80）。我们还发现，低（≤10,000拷贝/毫升）与高（>10,000拷贝/毫升）峰值病毒血症对ART恢复时或病毒再抑制时的CD4 T细胞计数没有影响（分别为P = 0.48，P = 0.88）。同样，病毒血症持续0-14天的个体与持续>28天的个体相比，从ATI前到病毒再抑制时CD4 T细胞计数的变化没有显著差异。
在我们的汇总分析中，高的峰值反弹pVL和更长的病毒血症持续时间并没有损害ART恢复后CD4 T细胞的恢复，这支持了在HIV-1治愈试验中采用更灵活的ATI的安全性。
