Comprehensive analysis of unique cases with extraordinary control over HIV replication
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 17, 2012
- Source ID
- 10.1182/blood-2011-10-381996
Entities
People
- Bennett A. Peterson
- Catherine A. Rehm
- Cheryl L. Chairez
- Claire W. Hallahan
- Daniel Mendoza
- Erin H. Graf
- Irini Sereti
- Jamieson H. Greenwald
- Jessica N. Hodge
- Joseph A. Kovacs
- Maria Salgado
- Mark Connors
- Nancy A. Cogliano
- Nicole A. Doria-rose
- Omar Sued
- Peter D. Burbelo
- Robert J. O'connell
- Robin L. Dewar
- Sara Jones
- Sarah A. Johnson
- Sheila A. Peel
- Stephen A. Migueles
- Tae-wook Chun
- Una O’doherty
- Ven Natarajan
- William L. Thompson
Organizations
- Fundación Huésped
- IrsiCaixa
- Johns Hopkins University
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- University of Pennsylvania
- Walter Reed Army Institute of Research