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Kaletra Protects Mitochondria
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T-cell marker activation, and mitochondrial membrane integrity after exposure to lopinavir, ritonavir or efavirenz on HIV-negative CD4+ lymphocytes
IAS Capetown July 2009
Reported by Jules Levin
Presented by James Scott (United States).
J. Scott1, S. O'Barr1, T. Sparrow2
1Western University of Health Sciences, College of Pharmacy, Pomona, United States, 2Abbott Laboratories, Abbott Park, United States
Background: Recent data suggest that although efavirenz (EFV) has a better rate of virologic suppression compared to lopinavir/ritonavir (LPV/r), LPV/r has a better CD4+ count response. While an earlier study showed no immunologic difference with protease inhibitors (PIs), it did not look at markers of T-cell activation. This study assessed the effect of LPV, RTV, LPV/r, and EFV on immune function of activated human CD4+ lymphocytes.
Methods: 24cc of blood was drawn from 16 HIV- controls (sample lost for 1 subject). Peripheral Blood Lymphocytes were washed and sub-cultured, then activated with IL-2. Cells were then exposed to 1.0uM LPV, 1.0uM RTV, LPV and RTV together, and 1.0uM EFV for 72 hours, or unexposed for control. Cells were stained with fluorochrome-tagged monoclonal antibody to CD4, CD25, CD38, and HLD-DR. Analysis of surface marker intensity was performed by flow cytometry, gated against CD4. PBL apoptosis was assessed using a mitochondrial membrane integrity assay [MitoProbe JC-1 assay kit for flow cytometry (M34152) molecular probes]. A system hardware/software error resulted in loss of data from some samples.
Results: No significant change in CD25, CD38 or HLA-DR receptor integrity was seen between cells treated with drug and control. There was an ∼40% increase in CD4+ receptor intensity with both LPV and EFV compared to control (n=7; p=0.02 and 0.03). Mitochondrial membrane integrity increased by more than 25% in LPV/r exposed cells (n=5; p=0.017), but not in other cells; EFV had no effect (n=13; p=0.2).
Conclusions: Both LPV and EFV improved CD4 receptor intensity. The combination of LPV/r improved apoptosis markers, which may explain the improved immunologic outcomes seen in ACTG 5142. The results of the T-cell activation markers do not explain the difference in CD4 response seen in that study. Further studies should assess other antiretroviral agents, and the clinical impact of these findings.
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