Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4(+) T cells.
Research paper by
Anwesha A Sanyal, Robbie B RB Mailliard, Charles R CR Rinaldo, Deena D Ratner, Ming M Ding, Yue Y Chen, Jennifer M JM Zerbato, Nicholas S NS Giacobbi, Narasimhan J NJ Venkatachari, Bruce K BK Patterson, Amanda A Chargin, Nicolas N Sluis-Cremer, Phalguni P Gupta
Although antiretroviral therapy can suppress HIV-1 infection to undetectable levels of plasma viremia, integrated latent HIV-1 genomes that encode replication-competent virus persist in resting CD4(+) T cells. This latent HIV-1 reservoir represents a major barrier to a cure. Currently, there are substantial efforts to identify therapeutic approaches that will eliminate or reduce the size of this latent HIV-1 reservoir. In this regard, a sensitive assay that can accurately and rapidly quantify inducible, replication-competent latent HIV-1 from resting CD4(+) T cells is essential for HIV-1 eradication studies. Here we describe a reporter cell-based assay to quantify inducible, replication-competent latent HIV-1. This assay has several advantages over existing technology in that it (i) is sensitive; (ii) requires only a small blood volume; (iii) is faster, less labor intensive, and less expensive; and (iv) can be readily adapted into a high-throughput format. Using this assay, we show that the size of the inducible latent HIV-1 reservoir in aviremic participants on therapy is approximately 70-fold larger than previous estimates.