Background Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies. Methods Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA >1,000 copies/mL). Results Late ART initiation was associated with higher rebound risk (shorter time to rebound), as compared to early ART. Higher pre-ART HIV RNA, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Less CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T Cells appeared to be the most relevant risk factors for time to rebound. Conclusion These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression.

中文翻译：

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中断抗逆转录病毒治疗后 HIV 反弹的病毒和免疫危险因素


背景 确定治疗中断后 HIV 反弹的危险因素对于设计有效的缓解策略至关重要。方法 在中断 ART 之前，分析苏黎世 HIV 原发感染队列 （ZPHI， N=73） 和 ACTG 研究 A5345 （N=44） 参与者的外周血单核细胞。我们测量了细胞相关 HIV RNA 、 总 HIV DNA 和前病毒多样性 （env 基因）。通过流式细胞术进行免疫表型分析。具有适应性 LASSO 惩罚的 Cox 比例风险 （PH） 模型和惩罚 Cox PH 模型确定了反弹时间的危险因素（HIV RNA >1,000 拷贝/mL）。结果 与早期 ART 相比，较晚开始 ART 与更高的反弹风险 （更短的反弹时间） 相关。ART 中断时 ART 前 HIV RNA 、 HIV 总 DNA 和细胞 HIV 转录增加与更高的反弹风险相关。较高的前病毒多样性与较高的反弹风险相关，但仅限于男性参与者和 ZPHI 队列中的参与者。ART 中断时 CD4+ T 细胞较少，效应细胞和终末分化 T 细胞比例较高，活化和耗竭的 T 细胞较多与较高的反弹风险相关，主要发生在早期治疗的参与者中。在慢性 HIV 治疗期间接受治疗的参与者中没有发现显著的免疫危险因素。在联合队列中，总 HIV DNA 和终末分化的 CD8+ T 细胞似乎是影响反弹时间的最相关危险因素。结论这些发现强调了早期 ART 开始的重要性，并表明基于病毒学、免疫学和人口学因素的定制干预措施可能有助于实现持续的病毒抑制。