Journal of Clinical Investigation · 2019 · 122 citations · 50 references
Life SciencesImmunologyInfectious DiseasesClinical ImmunologyMolecular VirologyVirologyAntiretroviral TherapyAntiviral TherapyViral InfectionsViral PersistenceViral ReplicationViral Rna BiologyCellular ProliferationEarly Antiretroviral TherapyHiv Antiretroviral TherapyProviral IntegrationViral Integration SitesViral Persistence MechanismsViral Replication Kinetics
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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Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez et al. · Proceedings of the National Academy of Sciences · 2008 · 1.9K citations · Full text
Life Sciences, Evolutionary Biology, Infectious Diseases +17
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
Ya‐Chi Ho, Liang Shan, Nina N. Hosmane et al. · Cell · 2013 · 1.5K citations · Full text