Defining Total Body AIDS Virus Burden: Implications for Curative Strategies

• Published in: Nature medicine Vol. 23; no. 11; pp. 1271 - 1276
• Main Authors: Estes, Jacob D., Kityo, Cissy, Ssali, Francis, Swainson, Louise, Makamdop, Krystelle Nganou, Del Prete, Gregory Q., Deeks, Steven G., Luciw, Paul, Chipman, Jeffrey, Beilman, Gregory, Hoskuldsson, Torfi, Khoruts, Alexander, Anderson, Jodi, Deleage, Claire, Jasurda, Jacob, Schmidt, Thomas, Hafertepe, Michael, Callisto, Samuel, Pearson, Hope, Reimann, Thomas, Schuster, Jared, Schoephoerster, Jordan, Southern, Peter, Perkey, Katherine, Shang, Liang, Wietgrefe, Steve, Fletcher, Courtney V., Lifson, Jeffrey D., Douek, Daniel C., McCune, Joseph M., Haase, Ashley T., Schacker, Timothy W.
• Format: Journal Article
• Language: English
• Published: 02.10.2017
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.4411

In the quest for a functional cure or eradication of HIV infection, we need to know how large the reservoirs are from which infection rebounds when treatment is interrupted. To that end, we quantified SIV and HIV tissue burdens in tissues of infected non-human primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs harbor more than 98 percent of the SIV RNA+ and DNA+ cells. While ART substantially reduced their numbers, vRNA+ cells were still detectable and their persistence was associated with relatively low drug concentrations in LT compared to peripheral blood. Prolonged ART also reduced the level of SIV and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 10 8 vDNA+ cells that potentially harbor replication competent proviruses, along with the evidence for continuing virus production in LT despite ART, identify two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore the challenges in developing “HIV cure” strategies that target multiple sources of virus production.