How to Define the Latent Reservoir: Tools of the Trade

Abstract

HIV is a devastating worldwide epidemic that has had substantial social and economic impacts throughout the globe. Due to the presence of a small pool of latently infected cells that persists during antiretroviral therapy (ART), HIV is not curable. Because of the high cost of ART and the lack of reliable accessibility across the globe, life-long ART is unfortunately not a feasible solution for the epidemic. Therefore, new strategies need to be developed and implemented to address HIV-1 infection. Several approaches toward this end are currently under investigation (Ebina et al. in Sci Rep 3:2510, 2013; Archin et al. in Nature 487:482-5, 2012; Elliott et al. in PLoS Pathog 10:e1004473, 2014; Rasmussen et al. in Lancet HIV 1:e13-e21, 2014; Tebas et al. in N Engl J Med 370:901-10, 2014; Archin et al. in Nat Rev Microbiol 12:750-64, 2014; Barton et al. in PLoS One 9:e102684, 2014; Sogaard et al. in PLoS Pathog 11:e1005142, 2015). Initial studies have proven promising, but have highlighted the need for sensitive and accurate assays to detect changes in very low concentrations of virus to allow confident interpretation of the success of curative approaches. This review will focus on assays that are currently available and the advantages and limitations of each.

Keywords: HIV biomarkers; HIV pathogenesis; Human immunodeficiency virus; Latent HIV; Persistent HIV; Review; Single-copy assay; Viral outgrowth assay.

Fig. 1

The many different stages of the HIV replication cycle and the response of the host’s immune system can be detected with sensitive assays to quantitate HIV in HIV-infected individuals on effective long-term antiretroviral therapy