Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller

Victoria E. Walker-Sperling, Christopher W. Pohlmeyer, Rebecca T. Veenhuis, Megan May, Krystle A. Luna, Allison R. Kirkpatrick, Oliver Laeyendecker, Andrea L. Cox, Mary Carrington, Justin R. Bailey, Roberto C. Arduino, Joel N. Blankson

Research output: Research - peer-reviewArticle

Abstract

HIV-1 controllers are patients who control HIV-1 viral replication without antiretroviral therapy. Control is achieved very early in the course of infection, but the mechanisms through which viral replication is restricted are not fully understood. We describe a patient who presented with acute HIV-1 infection and was found to have an HIV-1 RNA level of <. 100. copies/mL. She did not have any known protective HLA alleles, but significant immune activation of CD8. + T cells and natural killer (NK) cells was present, and both cell types inhibited viral replication. Virus cultured from this patient replicated as well in vitro as virus isolated from her partner, a patient with AIDS who was the source of transmission. Virologic breakthrough occurred 9. months after her initial presentation and was associated with an increase in CD4. + T cell activation levels and a significant decrease in NK cell inhibitory capacity. Remarkably, CD8. + T cell inhibitory capacity was preserved and there were no new escape mutations in targeted Gag epitopes. These findings suggest that fully replication-competent virus can be controlled in acute HIV-1 infection in some patients without protective HLA alleles and that NK cell responses may contribute to this early control of viral replication.

LanguageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Jul 6 2016

Fingerprint

HIV-1
T-cells
Viruses
Controllers
Chemical activation
Natural Killer Cells
T-Lymphocytes
HIV Infections
Alleles
Epitopes
RNA
Virus Replication
Acquired Immunodeficiency Syndrome
Mutation
Infection
Therapeutics
In Vitro Techniques

Keywords

  • CD8+ T cells
  • HIV controllers
  • HIV-1
  • NK cells
  • Transmission pair

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller. / Walker-Sperling, Victoria E.; Pohlmeyer, Christopher W.; Veenhuis, Rebecca T.; May, Megan; Luna, Krystle A.; Kirkpatrick, Allison R.; Laeyendecker, Oliver; Cox, Andrea L.; Carrington, Mary; Bailey, Justin R.; Arduino, Roberto C.; Blankson, Joel N.

In: EBioMedicine, 06.07.2016.

Research output: Research - peer-reviewArticle

Walker-Sperling VE, Pohlmeyer CW, Veenhuis RT, May M, Luna KA, Kirkpatrick AR et al. Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller. EBioMedicine. 2016 Jul 6. Available from, DOI: 10.1016/j.ebiom.2017.01.034
Walker-Sperling, Victoria E. ; Pohlmeyer, Christopher W. ; Veenhuis, Rebecca T. ; May, Megan ; Luna, Krystle A. ; Kirkpatrick, Allison R. ; Laeyendecker, Oliver ; Cox, Andrea L. ; Carrington, Mary ; Bailey, Justin R. ; Arduino, Roberto C. ; Blankson, Joel N./ Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller. In: EBioMedicine. 2016
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