1. ¹Infectious Diseases Unit, University Medical Center Hamburg-, Eppendorf, Hamburg, Germany
2. ²Present address: private, practice, Berlin, Germany
3. ³Department of Immunology, Laboratory Center, Berlin, Berlin, Germany
4. ⁴Department of Pediatric Hematology and Oncology, Hannover Medical, School, Hannover, Germany
5. ⁵EUFETS AG, Idar-Oberstein, Germany
6. ⁶Georg-Speyer-Haus, Frankfurt a.M., Germany
7. ⁷Fresenius AG, Bad Homburg, Germany
8. ⁸GANYMED Pharmaceuticals, AG, Mainz, Germany

Correspondence: Dorothee von Laer, Georg-Speyer-Haus, Paul-Ehrlich-Strasse 42–44, 60596 Frankfurt a.M., Germany. E-mail: laer@em.uni-frankfurt.de

^*These authors contributed equally to this work.Correspondence may also be addressed to Jan van Lunzen, Ambulanzzentrum des UKE, Bereich Infektiologie, Universitätsklinikum Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany. E-mail: v.lunzen@uke.uni-hamburg.de

Received 22 November 2006; Accepted 24 January 2007; Published online 13 March 2007.

Abstract

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.