14th International AIDS Conference Barcelona, Spain - July 7-12, 2002

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1345)

Sousa AE, Carneiro J, Grossman Z, Victorino R
Faculty of Medicine of Lisbon, Lisbon, Portugal

BACKGROUND: The causal relationships among CD4 cell depletion, HIV replication and immune activation are not well understood. HIV-2 infection, "nature's experiment" with inherently attenuated HIV disease, provides additional insights into this issue. METHODS AND

RESULTS: We stratified and paired groups of HIV-1 and HIV-2 infected patients whose levels of CD4 depletion fell in the same range and found that the two infections exhibited a similar imbalance in the naïve/memory-effector population ratios with comparable up-regulation of CD4 and CD8 cell-activation markers (HLADR, CD38, CD69, Fas molecule). Moreover, there was a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers, and a similar level of anergy, as assessed by the in-vitro lymphoproliferative responses to CD3 stimulation and to a panel of microbial antigens.

CONCLUSIONS: These findings are surprising considering that HIV2-infected patients at a given stage of CD4 depletion bear plasma viral loads two orders of magnitude lower than HIV1 viremia, and are known to have slower rates of CD4 T-cell decline and a better clinical prognosis. Our data are consistent with a direct causal relation between immune activation and CD4 cell depletion in HIV disease and only an indirect relation of these parameters to the virus replication rate.

020707
WeOrA1345

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