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Abstract
EARLY AND PERSISTENT HEMATOPOIESIS FAILURE IN SHIV INFECTED MACAQUES DESPITE EFFICIENT HAART
THIEBOT H, VASLIN B, LOUACHE F, DE REVEL T, VAINCHENKER W, DORMONT D, LE GRAND R
Background: To evaluate, in the model of macaques infected with a pathogenic simian/human chimeric virus (SHIV), the impact infection on bone marrow primitives or differentiated hematopoietic progenitor cells.
Materials and Methods: Three groups of four macaques were inoculated with 50 MID50 of SHIV89.P which expresses the env gene of the primary HIV-1 89.6 isolate in a SIVmac239 background. During primary infection, animals were treated twice a day with either placebo or with the association of AZT, 3TC and Indinavir (HAART). Virological and immunological parameters were followed during one year. Purified CD34+ bone marrow cells (over 99% pure) were used for the detection of long term culture-initiating cells (LTC-IC) or colony forming cells (CFC). A gag PCR was used for the detection of virus presence in bone marrow cells.
Results and conclusion: All the macaques were infected and exhibited a decrease of CFC, starting as early as primary infection. One year p.i., CFC decreased of approximately 56% of pre-infection values and a dramatic reduction (over 77%) of primitive long-term culture initiating cells was noticed. Virus DNA could not be evidenced in purified bone marrow cells. Hematopoietic failure could not be prevented by early HAART, although antiviral treatment during primary infection results in a significant reduction of viral load and prevention of dramatic circulating CD4+ T cell loss. No correlation could be established between impaired progenitor growth and CD4+ lymphopenia or plasma viremia. Finally, the consequences of CD34+ dysfunction on T lymphocyte production and homeostasis are under investigation.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
88
Suggested Citation
"THIEBOTH, et al.
EARLY AND PERSISTENT HEMATOPOIESIS FAILURE IN SHIV INFECTED MACAQUES DESPITE EFFICIENT HAART.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
88"
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