Journal Article

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Deeks, Steven G, Martinez-Picado, Javier, Autran, Brigitte, Richman, Douglas D, van Lunzen, Jan, Vella, Stefano, Schmitz, Joern E, Ahlers, Jeffrey, Katlama, Christine, Rouzioux, Christine, Miller, Michael, Sekaly, Rafick P

2013

Overview

Antiretroviral therapy for HIV infection needs lifelong access and strict adherence to regimens that are both expensive and associated with toxic effects. A curative intervention will be needed to fully stop the epidemic. The failure to eradicate HIV infection during long-term antiretroviral therapy shows the intrinsic stability of the viral genome in latently infected CD4T cells and other cells, and possibly a sustained low-level viral replication. Heterogeneity in latently infected cell populations and homoeostatic proliferation of infected cells might affect the dynamics of virus production and persistence. Despite potent antiretroviral therapy, chronic immune activation, inflammation, and immune dysfunction persist, and are likely to have important effects on the size and distribution of the viral reservoir. The inability of the immune system to recognise cells harbouring latent virus and to eliminate cells actively producing virus is the biggest challenge to finding a cure. We look at new approaches to unravelling the complex virus–host interactions that lead to persistent infection and latency, and discuss the rationale for combination of novel treatment strategies with available antiretroviral treatment options to cure HIV.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Acquired immune deficiency syndrome / AIDS / Anti-HIV Agents - pharmacology / Antiretroviral agents / Apoptosis / Biological and medical sciences / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - virology / CD8-Positive T-Lymphocytes - drug effects / CD8-Positive T-Lymphocytes - virology / Cell cycle / Cytokines / Deoxyribonucleic acid / DNA / DNA methylation / Drug Therapy, Combination - methods / Epigenetics / General aspects / genome / Heterogeneity / HIV / HIV infections / HIV Infections - drug therapy / HIV Infections - virology / HIV-1 - drug effects / HIV-1 - physiology / Human immunodeficiency virus / Human immunodeficiency virus 1 / Human viral diseases / Humans / Immune system / Infectious diseases / inflammation / Internal Medicine / Kinases / Lymphocytes / Medical sciences / Miscellaneous / Patients / Public health. Hygiene / Public health. Hygiene-occupational medicine / Receptors, CCR5 - drug effects / RNA, Viral - drug effects / RNA, Viral - physiology / therapeutics / toxicity / Transplants & implants / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Virus Latency - drug effects / virus replication / Virus Replication - drug effects / viruses