AIDS Treatment Update

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study comparing ritonavir/saquinavir with
ritonavir/indinavir is due to report initial
results mid-2001, and Glaxo Wellcome are
studying amprenavir/ritonavir against other
boosted PIs.
The combination of indinavir with ritonavir
has been under investigation for some time.
There is some evidence from the BEST study,
which randomised people on three times daily
indinavir (with nucleoside analogues) to either
remain on that regimen or switch to 800mg
twice daily indinavir with 100mg twice daily
ritonavir, that tolerability worsens after the
switch'. In this study there was more nausea in
switchers (probably because of ritonavir), and
more kidney stones (probably because of
higher blood levels of indinavir).
The DIRECT study is a pilot study of
indinavir/ritonavir (800/100mg) with 3TC/
abacavir in treatment naive individuals8.
Median viral load at baseline, in the first 80
participants for whom results are available,
was 102,000 copies, and median CD4 count
was 275 cells. Using an on treatment analysis,
22 of 28 (79%) people who reached 24 weeks
treatment had viral load below 50 copies.
Fifteen of 89 people enrolled developed flank
pain, a pre-cursor of kidney stones, and three
left the study for this reason. Overall, sixteen
people have left the study, six for drug-related
side-effects. 26 people had laboratory
abnormalities, two had raised triglycerides and
seven had raised cholesterol.
Future PIs
The next generation of PIs includes
Boerhinger Ingelheim's tipranivir and BristolMyers Squibb's BMS-232632.

In the UK at present, the once daily B MS PI
is only available through a blinded clinical
trial. 24 week data from a dose-ranging study
comparing the drug with three times daily
nelfinavir, with ddl/d4T have been reported'.
Participants were new to treatment, and
underwent a two-week PI monotherapy period.
After 24 weeks, the antiviral activity of the
BMS PI appeared similar to nelfinavir. The
most common side-effect in nelfinavir users
was diarrhoea, and nausea in BMS-232632
users. Though cholesterol and triglyceride
levels rose in the nelfinavir arm, they remained
unchanged in the BMS-232632 arms. The
BMS PI was associated with high levels of
bilirubin (the pigment found in bile), however.
This was severe in five cases, and seven people
became jaundiced.
There is no access to tipranivir in the U K at
present. Both of these PIs may have to
undergo the same where-should-they-be-placed
controversy which is currently dogging ABT378/r. Tipranivir may benefit from a ritonavir
baby-dose, as may Glaxo Wellcome's PI
amprenavir, and perhaps allow both drugs to
be dosed once daily",". Amprenavir recently
became available on prescription in the
European Union for use after a first PI. More
detailed information on these products is
available on our website, aidsmap.com.
Conclusions
Boosted PIs are a recent development which
allow easier dosing of PIs, and - it seems -
greater potency, but also potentially more
toxicity. Because some boosted PIs may be
effective in people with PI resistance it's
unclear whether they may be best used as
first-line therapy or later on, after other PIs
have failed.