Browsing by Author "Greenwald, Jamieson H."

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    Comprehensive analysis of unique cases with extraordinary control over HIV replication
    (2012) Mendoza, Daniela; Johnson, Sherry A.; Peterson, Brenda A.; Natarajan, Vanitha; Salgado, Marcela; Dewar, 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, Sara; Hallahan, Claire W.; Kovacs, Joseph A.; Sereti, Irini; Sued, Omar; Peel, Sheila A.; O'Connell, Robert J.; O'Doherty, Una; Chun, Tae-Wook; Connors, Mark; Migueles, Stephen A.
    True 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.