Journal Article

Defining total-body AIDS-virus burden with implications for curative strategies

Khoruts, Alexander, Douek, Daniel C, Deeks, Steven G, Hoskuldsson, Torfi, Luciw, Paul A, Swainson, Louise, Makamdop, Krystelle Nganou, Fletcher, Courtney V, Ssali, Francis, Beilman, Gregory J, Hafertepe, Michael, McCune, Joseph M, Haase, Ashley T, Schmidt, Thomas E, Del Prete, Gregory Q, Lifson, Jeffrey D, Reimann, Thomas, Estes, Jacob D, Shang, Liang, Schoephoerster, Jordan, Schacker, Timothy W, Callisto, Samuel P, Perkey, Katherine, Pearson, Hope, Jasurda, Jacob, Schuster, Jared, Deleage, Claire, Southern, Peter, Anderson, Jodi, Chipman, Jeffrey G, Kityo, Cissy, Wietgrefe, Stephen W

2017

Overview

Quantifying the total-body virus burden in HIV-infected individuals is necessary to understand viral persistence and guide development of cure strategies. Here, Estes et al . find a high burden of residual virus in tissues of SIV-infected monkeys and HIV-infected humans, and evidence of low-level viral replication, even under antiretroviral therapy. In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA + and DNA + cells. With ART, the numbers of virus (v) RNA+ cells substantially decreased but remained detectable, and their persistence was associated with relatively lower drug concentrations in LT than in peripheral blood. Prolonged ART also decreased the levels of SIV- and HIV-DNA + cells, but the estimated size of the residual tissue burden of 10 8 vDNA + cells potentially containing replication-competent proviruses, along with evidence of continuing virus production in LT despite ART, indicated two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore challenges in developing 'HIV cure' strategies targeting multiple sources of virus production.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/420/254 / 692/699/255/1901 / Acquired immune deficiency syndrome / AIDS / Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral therapy / Biomedicine / Cancer Research / Care and treatment / Deoxyribonucleic acid / Diagnosis / DNA / DNA, Viral - analysis / Highly active antiretroviral therapy / HIV / HIV - genetics / HIV - isolation & purification / HIV infection / HIV Infections - blood / HIV Infections - drug therapy / HIV Infections - virology / Human immunodeficiency virus / Humans / Infectious Diseases / Interruption / Lymph nodes / Lymphoid tissue / Lymphoid Tissue - virology / Metabolic Diseases / Molecular Medicine / Neurosciences / Peripheral blood / Primates / Proviruses / Ribonucleic acid / RNA / RNA viruses / RNA, Viral - analysis / Tissues / Viral Load / Viruses