Targeting the Latent Reservoir for HIV-1

• Published in: Immunity (Cambridge, Mass.) Vol. 48; no. 5; pp. 872 - 895
• Main Authors: Sengupta, Srona, Siliciano, Robert F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-05-2018; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; AIDS; Anti-Retroviral Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell proliferation; Decay rate; Deoxyribonucleic acid; DNA; Drug resistance; Genomes; Hepatitis; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunodeficiency; Immunological memory; Infections; Lymphocytes; Lymphocytes T; Memory cells; Models, Immunological; Pharmacology; Proviruses; Proviruses - drug effects; Proviruses - immunology; Replication; Viral Load - drug effects; Viral Load - immunology; Virus Latency - drug effects; Virus Latency - immunology; Virus Replication - drug effects; Virus Replication - immunology
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2018.04.030

Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir. The development of a successful cure strategy will most likely require understanding the mechanisms that maintain HIV-1 proviruses in a latent state and pathways that drive the proliferation of infected cells, which slows reservoir decay. In addition, a cure will require the development of effective immunologic approaches to eliminating infected cells. There is renewed optimism about the prospect of a cure, and the interventions discussed here could pave the way.
Developing a cure for HIV-1 requires understanding the mechanisms of HIV-1 persistence in the latent reservoir. In this review, we discuss historical and recent paradigms in the HIV-1 persistence field as well as novel immunologic and pharmacologic strategies for eliminating this reservoir.