PI Perspective #33
August 2001 View PDF En
español
Highlights from IAS 2001
The following are highlights from the 1st International AIDS Society
Conference on HIV Pathogenesis and Treatment held in Buenos Aires,
Argentina during July 2001.
Structured Intermittent Therapy
More data were presented from the National Institutes of Health
structured intermittent therapy study. Early data were reported
in PI Perspective #31. Ten people were started on seven days of
anti-HIV therapies [d4T + 3TC + indinavir (Crixivan) + low dose
ritonavir (Norvir)] followed by seven days off. The seven-day cycle
was chosen because in previous studies, including people who received
optimal anti-HIV therapy, it generally took at least seven days
before viral loads climbed back up to detectable levels (over 500
copies/ml HIV RNA) after a therapy interruption. All ten people
who participated in this study had taken and responded well to therapy
before. As a result, at the start of the study, they had an average
CD4+ cell count of about 800. Five volunteers have been in the study
for more than six months and an additional three for more than a
year. All have undetectable viral loads (below 500 copies/ml) although
some have had intermittent blips. An interesting observation was
that people who stopped therapy for ten days or longer were more
likely to have a blip in viral load. Everyone experienced a significant
decrease in triglyceride and cholesterol levels, commonly increased
due to the protease inhibitors, especially ritonavir. Further, there
have been no indications of resistance developing to any anti-HIV
drugs nor are there signs that HIV is replenishing the sites where
it likes to hide, such as the lymph nodes.
Tipranavir
Study results were presented for tipranavir, a new protease inhibitor
being developed by Boehringer Ingelheim. Considerable interest in
this drug is driven by data suggesting that it remains active against
HIV resistant to most other protease inhibitors. One study compared
1,200mg tipranavir taken twice a day to either 300mg or 1,200mg
tipranavir together with 200mg ritonavir taken twice daily. This
was only a 14-day study and none of the 31 volunteers had taken
anti-HIV therapy before. At study end, there was an average viral
load reduction of about 1.5 log (32-fold) among the two groups on
tipranavir with ritonavir and about 0.7 log (5-fold) reduction among
those taking tipranavir alone. Side effects included diarrhea in
all three groups and nausea among those on the high dose tipranavir/ritonavir
combination.
A second study involved 41 people who had previously taken multiple
regimens that included protease inhibitors but not non-nucleoside
reverse transcriptase inhibitors (NNRTIs). At the beginning, participants
took twice daily regimens of either 1,200mg tipranavir + 100mg ritonavir
or 2,400mg tipranavir + 200mg ritonavir. They also received the
NNRTI efavirenz (Sustiva) and one new nucleoside reverse transcriptase
inhibitor (NRTI). During the study a new formula of tipranavir was
developed and people on the 1,200mg and 2,400mg doses were changed
to 500mg and 1,000mg of the new formula respectively. The dosing
schedule and dose of ritonavir was not changed. After 48 weeks,
79% of those on the lower dose of tipranavir had viral loads below
400 copies/ml and 68% were below 50 copies. Of those on the higher
dose, 50% had less 400 copies/ml and 41% had less than 50 copies.
In other words, those receiving the lower dose combination had more
pronounced viral load reductions—a strange outcome. Some researchers
speculate this may be due to poorer adherence on the higher dose
regimen. Another possible explanation is that the new formulation
may not be as stable or effective as hoped. The most common side
effects included diarrhea, nausea, headache, dizziness, fatigue
and abnormal dreams.
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