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Highly active antiretroviral therapy corrects hematopoiesis in HIV-1 infected patients: interest for peripheral blood stem cell-based gene therapy

Baillou, Claude; Simon, Anne; Leclercq, Virginie; Azar, Nabih; Rosenzwajg, Michele; Herson, Serge; Klatzmann, David; Lemoine, François M

Clinical Science

Objectives: To study, in asymptomatic HIV-1-infected (HIV+) patients, whether peripheral blood hematopoietic progenitor/stem cells (PBPC) mobilized by granulocyte colony stimulating factor (G-CSF), can be used as a source of cells for retroviral gene therapy.

Design: PBPC from two groups of HIV+ patients (treated or untreated by highly active antiretroviral therapy) and from seronegative donors were mobilized with G-CSF.

Methods: PBPC collected by leukapheresis were enriched for CD34 cells, immunophenotypically and functionally characterized, cultured and infected with retroviral vectors. HIV proviral integration was studied on fresh and cultured cells.

Results: G-CSF moderately and transiently increased the viral load in untreated patients only, and induced in both groups of HIV+ patients mobilization of percentages and numbers of CD34 cells comparable to those of seronegative volunteers. The most immature CD34 cell subset, the clonogenic progenitor and long-term culture initiating cells were significantly decreased in leukapheresis products and CD34-enriched fractions from untreated HIV+ patients but not in those from treated HIV+ patients. Cell cycle activation and growth factor responses of CD34 cells from both groups of HIV+ patients were not different from those of the control group. Culture and retroviral infection of CD34 cells from HIV+ patients did not enhance HIV replication, and yielded transduction levels similar to those obtained using CD34 cells from seronegative donors.

Conclusions: G-CSF-mobilized PBPC can be safely used for HIV retroviral gene therapy in asymptomatic treated patients while highly active antiretroviral therapy would control the G-CSF-induced increase in viral load and correct the defective hematopoiesis observed in untreated patients, without inhibiting the retroviral transduction of PBPC.

From the Biologie et Thérapeutique des Pathologies Immunitaires, UMR CNRS 7087 C.E.R.V.I. and Internal Medicine Department, UPMC, Hospital Pitié Salpêtrière, Paris, France.

Correspondence to F. M. Lemoine, Biologie et Thérapeutique des Pathologies Immunitaires, UMR CNRS 7087-C.E.R.V.I.-UPMC-Groupe hospitalier Pitié Salpêtrière, 83, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.

Received: 9 August 2002; revised: 25 October 2002; accepted: 5 November 2002.

© 2003 Lippincott Williams & Wilkins, Inc.