Treatment Issues Vol. 11, no. 2

v ISSUES
I
(U

times a day of the new, more absorbable version of saquinavir (the "soft gel capsule" containing saquinavir formulated with special
lipids which quadruple the proportion of
saquinavir absorbed by the intestines). At 12
weeks, viral loads were down 2.0 logs (99%),
with eight of 13 participants (62%) at undetectable levels (below 500 copies/ml). CD4
counts were up by 105.
There are 12 possible double protease inhibitor
combinations just counting the three protease
inhibitors on the market and nelfinavir. Many of
these may be feasible combinations in terms of
tolerability, drug-drug metabolic interactions and
lack of cross-resistance. Bear in mind that ritonavir works with saquinavir and possibly ABT-378
above all because of ritonavir's particular metabolic properties. By blocking the hepatic breakdown of the other protease inhibitors, ritonavir
raises them to highly potent levels.

Conversely, there may be interference
between protease inhibitors because they compete for the same binding sites on the protease
enzyme. By getting in each other's way, two
protease inhibitors would have a combined
effect less than the sum of their individual
effects (this is termed antagonism), never mind
the hoped for synergy, which occurs when the
combined effects are greater than the sum of the
individual ones. At the Retrovirus Conference,
Merck and Roche researchers reported preliminary results indicating that indinavir administered concurrently with saquinavir raises the
latter's blood levels five to eight times (abstract
608), similar to what nelfinavir does. But a
team from Harvard Medical School determined
that in lab culture at least, the interactive
effects of indinavir and saquinavir are antagonistic, except at low doses in wild type virus
(abstracts 11 and 188).

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