Comprehensive analysis of unique cases with extraordinary control over HIV replication

Daniel Mendoza, Sarah A. Johnson, Bennett A. Peterson, Ven Natarajan, Maria Salgado, Robin L. Dewar, Peter D. Burbelo, Nicole A. Doria-Rose, Erin H. Graf, Jamieson H. Greenwald, Jessica N. Hodge, William L. Thompson, Nancy A. Cogliano, Cheryl L. Chairez, Catherine A. Rehm, Sara Jones, Claire W. Hallahan, Joseph A. Kovacs, Irini Sereti, Omar SuedSheila A. Peel, Robert J. O'Connell, Una O'Doherty, Tae Wook Chun, Mark Connors, Stephen A. Migueles*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4645-4655
Number of pages11
JournalBlood
Volume119
Issue number20
DOIs
StatePublished - 17 May 2012
Externally publishedYes

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