Quantitative evaluation and optimization of co-drugging to improve anti-HIV latency therapy.

ABSTRACT: Human immunodeficiency virus 1 (HIV) latency remains a significant obstacle to curing infected patients. One promising therapeutic strategy is to purge the latent cellular reservoir by activating latent HIV with latency-reversing agents (LRAs). In some cases, co-drugging with multiple LRAs is necessary to activate latent infections, but few studies have established quantitative criteria for determining when co-drugging is required. Here we systematically quantified drug interactions between histone deacetylase inhibitors and transcriptional activators of HIV and found that the need for co-drugging is determined by the proximity of latent infections to the chromatin-regulated viral gene activation threshold at the viral promoter. Our results suggest two classes of latent viral integrations:

SUBMITTER: Wong VC 

PROVIDER: S-EPMC4501041 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature