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130 Correlation between Lymphoid Dendritic Cell Recovery and Better Infection Control in Primary HIV Infection: Immunotherapy Needed in Addition to Therapeutic Vaccines?
S. Kahi1, J. Pacanowski1, M. Baillet1, P. Lebon2, C. Deveau3, C. Goujard3, L. Meyer3, E. Oksenhendler4, M. Sinet3, and A. Hosmalin*1
1Inst. Cochin de Génétique Moléculaire, Paris, France; 2Hosp. St-Vincent de Paul, Paris, France; 3PRIMO Cohort Study Group, Hosp. de Bicêtre, Le Kremlin-Bicêtre, Paris, France; and 4Hosp. St Louis, Paris, France
Background: Successful immunological control of HIV infection is only achieved in rare individuals. Dendritic cells (DC) are absolutely required to activate naive T cells. Two major blood precursor populations are found: myeloid DC, which express CD11c+ and the GM-CSF receptor and secrete IL-12, and lymphoid DC, which express the IL-3 receptor (CD123) and secrete type I interferons (IFNs). These IFNs are strong effectors of the innate antiviral immunity. We had previously found decreased blood CD11c+ DC in HIV chronically infected patients.
Methods: In this study, we have used rare event analysis of 3- or 4-colour flow-cytometry data. We have longitudinally studied 13 patients during primary infection, 26 to 57 days after contamination, before initiation of highly active antiretroviral therapy (HAART), and then after 6(12 months of HAART.
Results: Before treatment, lymphoid and myeloid DC numbers were dramatically reduced in the 13 HIV+ patients compared with 13 controls (p = 0.0002 and 0.001, respectively). After 6(12 months of highly active antiretroviral therapy, DC subpopulation average numbers remained low, but lymphoid DC numbers increased again in 5/13 patients. A strong correlation was found between this increase and CD4 T-cell count increase (p = 0.0009) and plasmatic viral load decrease (p = 0.009).
Conclusions: Current therapeutic vaccination protocols aim at stimulating naive T cells still able to recognize HIV epitopes in patients treated by HAART, but immunocompromised by HIV infection. DC restoration by immunotherapy (such as GM-CSF, IFN-alpha) may be necessary to obtain efficient antigen presentation of these therapeutic vaccines. Successful immunological control of HIV infection might then be obtained under HAART and allow treatment interruption.
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