Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller.
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 <100copies/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 9months 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.
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Victoria E
VE
Walker-Sperling
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher W
CW
Pohlmeyer
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rebecca T
RT
Veenhuis
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Megan
M
May
Department of Medicine, University of Texas MD Anderson Cancer Center, Austin, TX, USA.
Krystle A
KA
Luna
Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD, USA.
Allison R
AR
Kirkpatrick
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD, USA.
Oliver
O
Laeyendecker
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Andrea L
AL
Cox
Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Mary
M
Carrington
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Justin R
JR
Bailey
Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Roberto C
RC
Arduino
Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jblanks@jhmi.edu.
Joel N
JN
Blankson
D000483:Alleles; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D019562:Viral Load / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D006680:HLA Antigens
CD8+ T cells; HIV controllers; HIV-1; NK cells; Transmission pair