Journal Article

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

Anderson, Elizabeth M., Wells, Daria, Bale, Michael J., Sobolewski, Michele D., Kearney, Mary F., Wiegand, Ann, Keele, Brandon F., Hughes, Stephen H., Deeks, Steven G., Shao, Wei, Coffin, John M., Patro, Sean C., McManus, William R., Spindler, Jonathan, Wu, Xiaolin, Mellors, John W., Musick, Andrew, Musick, Victoria K., Milush, Jeffrey M., Halvas, Elias K., Hoh, Rebecca, Cyktor, Joshua C.

2019

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Adult / Anti-Retroviral Agents - administration & dosage / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Biomedical research / Blood cells / Cell proliferation / Cell Proliferation - drug effects / Dolutegravir / Drug resistance / Female / Follow-Up Studies / Gene Expression Regulation, Viral - drug effects / Health aspects / Highly active antiretroviral therapy / HIV / HIV Infections - drug therapy / HIV Infections - metabolism / HIV Infections - pathology / HIV Infections - virology / HIV-1 - physiology / Human immunodeficiency virus / Humans / Integration / Lymph nodes / Lymph Nodes - metabolism / Lymph Nodes - pathology / Lymph Nodes - virology / Male / Mutation / Peripheral blood / Proviruses / Replication / Ribonucleic acid / RNA / RNA, Viral - biosynthesis / RNA, Viral - genetics / Virus replication / Virus Replication - drug effects