HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy

Author:

McManus, William R

Bale, Michael J

Spindler,Jon

Wiegand,Ann

Musick,Andrew

Patro,Sean

Sobolewski, Michele D

Musick, Victoria K

Anderson, Elizabeth M

Cyktor, Joshua C

Halvas, Elias K

Shao,Wei

Wells,Daria

Wu,Xiaolin

Keele,Brandon

Milush, Jeffrey M

Hoh, Rebecca

Mellors, John W

Hughes,Stephen

Deeks, Steven G

Coffin, John M

Kearney,Mary
Author Address

HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA., Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Department of Medicine, UCSF, San Francisco, California, USA., Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, USA.,

Abstract:

To investigate the possibility that HIV-1 replication in lymph nodes sustains the reservoir during ART, we looked for evidence of viral replication in 5 donors after up to 13 years of viral suppression. We characterized proviral populations in lymph nodes and peripheral blood before and during ART, evaluated the levels of viral RNA expression in single lymph node and blood cells, and characterized the proviral integration sites in paired lymph node and blood samples. Proviruses with identical sequences, identical integration sites, and similar levels of RNA expression were found in lymph nodes and blood samples collected during ART, and no single sequence with significant divergence from the pretherapy population was present in either blood or lymph nodes. These findings show that all detectable persistent HIV-1 infection is consistent with maintenance in lymph nodes by clonal proliferation of cells infected before ART and not by ongoing viral replication during ART.

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Author Address