A Widely-Distributed Hiv-1 Provirus Elimination Assay to Evaluate Latency-Reversing Agents in Vitro

Authors:
Preprint
Publisher website
Google Scholar
Abstract
Persistence of HIV-1 latent reservoir cells during antiretroviral therapy is a major obstacle for curing HIV-1. Latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells; however, there are few useful models for evaluating LRA activity in vitro . Here we established a long-term cell culture system harboring thousands of different HIV-1-infected cell clones with a wide distribution of HIV-1 provirus similar to that observed in vivo . A combination of an LRA and antiretroviral therapy (ART) significantly reduced viral rebound upon treatment interruption. Experimental results and mathematical modeling demonstrated that addition of LRA to ART showed latency-reversing effect and contributed to the eradication of replication competent HIV-1. The widely distributed intact provirus elimination (WIPE) assay can be used to optimize therapeutic against HIV-1 latency and investigate mechanistic insights into the clonal selection of heterogeneous HIV-1-infected cells.

This publication has 32 references indexed in Scilit: