TY - JOUR
T1 - Comprehensive analysis of unique cases with extraordinary control over HIV replication
AU - Mendoza, Daniel
AU - Johnson, Sarah A.
AU - Peterson, Bennett A.
AU - Natarajan, Ven
AU - Salgado, Maria
AU - Dewar, Robin L.
AU - Burbelo, Peter D.
AU - Doria-Rose, Nicole A.
AU - Graf, Erin H.
AU - Greenwald, Jamieson H.
AU - Hodge, Jessica N.
AU - Thompson, William L.
AU - Cogliano, Nancy A.
AU - Chairez, Cheryl L.
AU - Rehm, Catherine A.
AU - Jones, Sara
AU - Hallahan, Claire W.
AU - Kovacs, Joseph A.
AU - Sereti, Irini
AU - Sued, Omar
AU - Peel, Sheila A.
AU - O'Connell, Robert J.
AU - O'Doherty, Una
AU - Chun, Tae Wook
AU - Connors, Mark
AU - Migueles, Stephen A.
PY - 2012/5/17
Y1 - 2012/5/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84861203962&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-10-381996
DO - 10.1182/blood-2011-10-381996
M3 - Article
C2 - 22490332
AN - SCOPUS:84861203962
SN - 0006-4971
VL - 119
SP - 4645
EP - 4655
JO - Blood
JF - Blood
IS - 20
ER -