Insights into the HIV-1 Latent Reservoir and Strategies to Cure HIV-1 Infection

Abstract

Since the first discovery of human immunodeficiency virus 1 (HIV-1) in 1983, the targeted treatment, antiretroviral therapy (ART), has effectively limited the detected plasma viremia below a very low level and the technique has been improved rapidly. However, due to the persistence of the latent reservoir of replication-competent HIV-1 in patients treated with ART, a sudden withdrawal of the drug inevitably results in HIV viral rebound and HIV progression. Therefore, more understanding of the HIV-1 latent reservoir (LR) is the priority before developing a cure that thoroughly eliminates the reservoir. HIV-1 spreads through both the release of cell-free particles and by cell-to-cell transmission. Mounting evidence indicates that cell-to-cell transmission is more efficient than cell-free transmission of particles and likely influences the pathogenesis of HIV-1 infection. This mode of viral transmission also influences the generation and maintenance of the latent reservoir, which represents the main obstacle for curing the infection. In this review, the definition, establishment, and maintenance of the HIV-1 LR, along with the state-of-the-art quantitative approaches that directly quantify HIV-1 intact proviruses, are elucidated. Strategies to cure HIV infection are highlighted. This review will renew hope for a better and more thorough cure of HIV infection for mankind and encourage more clinical trials to achieve ART-free HIV remission.