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Researchers Find AIDS Drugs Cause T Cell Death in Healthy, HIV Negative
Patients!

In the June 2, 2002 issue of Journal of Virology, researchers report an
astounding discovery: The protease inhibitor drugs Crixivan (indinavir) and
Invarase (saquinavir) caused T cell death in healthy HIV negative donor
blood in three separate experiments.

Authors Estaquier et al note: 'We treated PBMC [peripheral blood cells‚Ä*cells
circulating in the blood] from HIV-seronegative healthy donors with
increasing concentrations of IDV [indinavir], SQV [saquinavir], or ddI for 3
days and monitored T-cell proliferation and cell death. Both IDV and SQV
decreased T-cell proliferation mediated by CD3 MAb in three independent
experiments performed with healthy donor cells with a mean decrease for SQV
of 53% +/- 15% and a mean decrease for IDV of 48% +/- 12%.'

In other words, three experiments showed Crixivan and Invarase decreased
T-cell proliferation in the blood of healthy HIV-negative donors‚Ä*in the case
of Invarase, by more than half.

The following Reuters article glosses over the damning data and puts a
somewhat favorable spin on the findings with an equivocal summary statement
that 'protease inhibitors have the potential for both beneficial and
detrimental effects on CD4+ T cells...' (The study abstract is found at the
end of this emailer)

Protease Inhibitors May Influence HIV-1 Associated CD4+ T-Cell Death

NEW YORK (Reuters Health) Jul 02 - Studies of factors associated with
peripheral blood T-cell apoptosis in HIV-1 infection indicate that
antiretroviral agents may influence such processes independently of their
antiretroviral effects.

Dr. Jerome Estaquier of the Institut Pasteur in Paris, France and colleagues
note that T-cell apoptosis plays an important part in the pathogenesis of
HIV infection.

To investigate, the researchers incubated CD4+ T cells from healthy donors
in the presence of HIV-1. Even without T-cell stimulation, this induced C95
expression and primed the cells for CD95- or CD3-mediated cell death.

Use of the reverse transcriptase inhibitor didanosine did not affect
CD95-mediated CD4 T-cell death, showing that such apoptosis does not depend
on CD4 T-cell infection. This suggests, say the investigators, that 'HIV-1
triggers at least two distinct death pathways.'

One pathway, they indicate, involves CD95 and does not require viral
replication, the other appears to be an independent viral-replication
mediated pathway.

In further studies, the team found that addition of the protease inhibitor
saquinavir at a concentration of 0.2 M decreased HIV-mediated CD95
expression and thus cell death. However, addition of saquinavir or indinavir
at concentrations of 10 M induced a loss of mitochondrial membrane potential
and cell death.

Thus, the investigators conclude, 'protease inhibitors have the potential
for both beneficial and detrimental effects on CD4+ T cells independent of
their antiretroviral effects.'

Journal of Virology 2002;76:5966-5973.

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