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What do you think?
      #43264 - 11/08/02 07:03 AM

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

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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Re: What do you think? new
      #43271 - 11/08/02 07:57 AM

It has been well known that anti-HIV as well as many other medications from various classes for various diseases/conditions have direct toxic effect on the immune system. This is in no way a new piece of information, just a study of certain drugs.

Many antibiotics also cause suppression of the immune system cells, and some have proven to lead to mitochondrial damage on a level similar to NRTI/PI/NNRTI drugs. Bactrim/Septra for example, has been well known to cause mitochondrial damage and immune suppression.

This probably just reinforces the deaths that occurred in the early days of treatment for this disease, as such (now known) toxic levels of the medications (AZT for example) used at the time. It was discovered that not only were the medications suppressing HIV replication, but also development and functioning of the immune cells and causing cellular death of many classes of cells, not just the immune cells.

This is just one more example of the difficulty of managing any long term disease or condition with medications. Other examples would include diabetes, allergies, asthma, epilepsy and a whole host of other conditions that we now provide some prolonging of quality of life with medications. They continue to refine treatment and medications as fast as possible (which seems much to slow for what we would like).

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Reged: 04/16/01
Posts: 438
Loc: Boston
WHY Would you? new
      #43287 - 11/08/02 02:56 PM

Why would you test HIV medications on healthy negative people. The same could be said for the Damage that would occur on healthy patients with no sign of cancer that were given chemo or radiation therapy. It would not have good effects on them and would probably do major damage to their health, however use chemo or radiation therapy on someone who has cancer and it can save their life.


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