HIV-1 is able to persist in the face of potent antiretroviral therapy (ART). A number of strategies are being explored to allow ART-free viral remission or viral eradication. In order to gauge the progress of these strategies, assays with which to measure viral reservoir size and activity are needed. In a large percentage of aviremic individuals on suppressive ART, viral transcripts can be detected in peripheral blood CD4⁺ T cells. While this cell-associated RNA has been considered as a marker of viral reservoir activity, it is unclear whether cell-associated viral transcripts in aviremic individuals originate from biologically competent proviruses as opposed to being a product of abortive transcription from defective proviruses. We assessed whether cell-associated viral RNA in peripheral blood CD4⁺ T cells from aviremic individuals on ART originated from biologically competent proviruses. We demonstrate that cell-associated viral RNA transcripts were highly related to viral sequences obtained by ex vivo outgrowth. This relationship was also observed when viral transcription in the outgrowth cultures was limited to donor CD4⁺ T cells. Our study indicates that cell-associated viral RNA warrants further consideration as a viral reservoir surrogate in individuals on suppressive ART.

面对有效的抗逆转录病毒疗法 (ART)，HIV-1 能够持续存在。正在探索多种策略以实现无 ART 病毒缓解或病毒根除。为了衡量这些策略的进展，需要用于测量病毒库大小和活性的分析。在接受抑制性 ART 的大部分无病毒血症个体中，可以在外周血 CD4 ⁺ T 细胞中检测到病毒转录物。虽然这种与细胞相关的 RNA 被认为是病毒库活动的标志物，但尚不清楚无病毒血症个体中细胞相关的病毒转录物是否源自具有生物活性的原病毒，而不是来自有缺陷的原病毒的中止转录的产物。我们评估了外周血 CD4 中的细胞相关病毒 RNA⁺来自接受 ART 的无病毒血症个体的 T 细胞源自具有生物活性的原病毒。我们证明细胞相关的病毒 RNA 转录本与通过体外生长获得的病毒序列高度相关。当生长培养物中的病毒转录仅限于供体 CD4 ⁺ T 细胞时，也观察到了这种关系。我们的研究表明，细胞相关病毒 RNA 值得进一步考虑作为接受抑制性 ART 个体的病毒库替代物。