Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals.
Some individuals remain inexplicably seronegative and lack evidence for human immunodeficiency virus type 1 (HIV-1) infection by conventional serologic or virologic testing despite repeated high-risk virus exposures. Here, we examined 10 exposed seronegative (ES) individuals exhibiting HIV-1-specific cytotoxicity for the presence of HIV-1. We discovered HIV-1 DNA in resting CD4(+) T cells (mean, 0.05 +/- 0.01 copies per million cells) at multiple visits spanning 69 to 130 weeks in two ES individuals at levels that were on average 10(4)- to 10(6)-fold lower than those of other HIV-1-infected populations reported. Sequences of HIV-1 envelope and gag genes remained markedly homogeneous, indicating little to undetectable virus replication. These results provide the evidence for HIV-1 infection in ES individuals below the detection limit of standard assays, suggesting that extraordinary control of infection can occur. The two HIV-infected ES individuals remained healthy and were not superinfected with other HIV-1 strains despite continued high-risk sexual exposures to multiple HIV-infected partners. Understanding the mechanisms that confer diminished replicative capacity of HIV-1 in these hosts is paramount to developing strategies for protection against and control of HIV-1 infection.
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle 98195, USA. tzhu@u.washington.edu
Tuofu
T
Zhu
Lawrence
L
Corey
Yon
Y
Hwangbo
Jean M
JM
Lee
Gerald H
GH
Learn
James I
JI
Mullins
M Juliana
MJ
McElrath
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D020276:HIV Long-Term Survivors; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D010802:Phylogeny; D012309:Risk-Taking; D017422:Sequence Analysis, DNA; D012747:Sexual Partners; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments