Mendoza, DanielaJohnson, Sherry A.Peterson, Brenda A.Natarajan, VanithaSalgado, MarcelaDewar, Rebecca L.Burbelo, Peter D.Doria-Rose, Nicole A.Graf, Erin H.Greenwald, Jamieson H.Hodge, Jessica N.Thompson, William L.Cogliano, Nancy A.Chairez, Cheryl L.Rehm, Catherine A.Jones, SaraHallahan, Claire W.Kovacs, Joseph A.Sereti, IriniSued, OmarPeel, Sheila A.O'Connell, Robert J.O'Doherty, UnaChun, Tae-WookConnors, MarkMigueles, Stephen A.2024-05-232024-05-232012Mendoza, D., Johnson, S. A., Peterson, B. A., Natarajan, V., Salgado, M., Dewar, R. L., Burbelo, P. D., Doria-Rose, N. A., Graf, E. H., Hodge, J. N., Thompson, W. L., Cogliano, N. A., Chairez, C. L., Rehm, C. A., Jones, S., Hallahan, C. W., Kovacs, J. A., Sereti, I., Sued, O., Peel, S. A., O’Connell, R. J., O’Doherty, U., Chun, T.-W., Connors, M., & Migueles, S. A. (2012). Comprehensive analysis of unique cases with extraordinary control over HIV replication. Blood.DOI: 10.1182/blood-2011-10-381996https://repositorio.huesped.org.ar/handle/123456789/1084True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8+ T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8+ T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.Extraordinary controlHIV replicationComprehensive analysis