Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus.
Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during anti-retroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.
van Lunzen
Jan
J
Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. v.lunzen@uke.uni-hamburg.de
Glaunsinger
Tobias
T
Stahmer
Ingrid
I
von Baehr
Volker
V
Baum
Christopher
C
Schilz
Andrea
A
Kuehlcke
Klaus
K
Naundorf
Sonja
S
Martinius
Holger
H
Hermann
Felix
F
Giroglou
Tsanan
T
Newrzela
Sebastian
S
Müller
Ingrid
I
Brauer
Francis
F
Brandenburg
Gunda
G
Alexandrov
Alexander
A
von Laer
Dorothee
D
D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000276:immunology; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load
C515020:C46 HIV-1 fusion inhibitory peptide; D011993:Recombinant Fusion Proteins