Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals

J Virol. 2003 Jun;77(11):6108-16. doi: 10.1128/jvi.77.11.6108-6116.2003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • CD4-Positive T-Lymphocytes / virology*
  • DNA, Viral / blood*
  • HIV Envelope Protein gp120 / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Long-Term Survivors*
  • HIV Seronegativity / immunology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • HIV-1 / isolation & purification
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Phylogeny
  • Risk-Taking
  • Sequence Analysis, DNA
  • Sexual Partners
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Load

Substances

  • DNA, Viral
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments

Associated data

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