AIDS Treatment Update

BStat m
strtn wit Pi

The protease inhibitor (PI) class of drugs was
the first associated with the big swings towards
better and longer life and health seen in people
with HIV in industrialised countries in the late
1990s. As alternatives became available which
seemed no less potent, but promised simpler
dosing, PIs became less popular. Now they're
experiencing something of a comeback.
Taking one PI with a low dose of ritonavir
tends to boost levels of the other drug, and
this has been a good thing for several different
reasons. In the case of hard-gel saquinavir, it
has allowed a drug which was only weakly
potent as a sole PI because of poor
absorption, to be used effectively. With
indinavir, the addition of ritonavir allows twice
daily dosing of both drugs and a removal of
dietary restrictions. And with a new PI, ABT378 (lopinavir), there's some evidence that the
high blood levels obtained through the
ritonavir boost can overcome resistance to
PIs, and therefore allow people to benefit from
a second PI-containing regimen.
ABT-378/r in first-line therapy
ABT-378/r (lopinavir/ritonavir) has now been
approved for use in the US, under the brandname Ka/etra, and will soon come up for
consideration by European Union drug
licensing authorities. It is produced by Abbott
Laboratories, who also make ritonavir.
There have been two major studies
investigating its use in first-line therapy. Study
M97-720 randomised 100 treatment naive
people, with viral load above 5,000 copies, to
receive one of three ABT-378/r doses, taken
twice daily together with d4T and 3TC2. After
48 weeks, everyone who was not already
taking ABT-378/r at the 400mg/100mg twice
daily dose was switched to that dose.
At entry, median viral load was 63,000 copies
and median CD4 count was 326 cells. After 96
weeks of treatment, 78% had viral load below
50 copies using an intent to treat analysis,
(see sidebar page 9 - analysing data).
According to the on treatment analysis the
proportion below 50 copies was 92%.
Fifteen people left the study at or before 108
weeks, in three cases for study drug-related
side-effects. The most common side-effects
were diarrhoea (25%) and nausea (15%).
Raised cholesterol and triglycerides were seen
in 15% and 13% respectively, but as values at
entry were not reported, it's unclear if these
were associated with treatment.
Study M98-863 compared ABT-378/r/d4T/
3TC with nelfinavir/d4T/3TC in 653 people
who were new to treatment and had viral load
above 400 copies'. Treatment was blinded and
was allocated at random. Nelfinavir was given
three times daily, though a switch to twice
daily was allowed at 24 weeks.
At entry, median viral load was 79,000 copies
and median CD4 count was 259 cells. By
intent to treat analysis, the proportion with
viral load below 50 copies at 48 weeks was
67% for ABT-378/r and 52% for nelfinavir.
By on treatment analysis, proportions are
83% and 68% respectively. These differences
are significant and reflect results from 262
ABT-378/r users and 251 nelfinavir users who
had reached the 48 week point.
There was no difference in side-effects and
laboratory abnormalities between groups,
except for a higher incidence of raised