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A Care Overview of the Retrovirus Conference
By Paul Benson, D.O.
Michigan HIV News, Spring 2002 issue feature
Over 3,500 clinicians and researchers met in Seattle, Washington for the 9th
Conference on Retroviruses and Opportunistic Infections, February 24-28, 2002.
By far the biggest issue from this year's conference is lipodystrophy. It still
remains elusive and difficult to understand.
Lipodystrophy
This can be abnormal fat accumulation (usually in the abdomen or behind the
neck), fat loss (lipoatrophy) which is usually in the face or arms and legs, and
dyslipidemia (abnormally high cholesterol and/or triglyercides). There are
several possible explanations for this observed syndrome. One belief is that as
people are doing better, the immune system rebuilds itself, and this rebuilding
may be the cause of lipodystrophy. Ironically, it may be that the more immune
compromised you start off (the lower the CD4 count) and the healthier you get (a
larger the increase in CD4 cells), the more probability you have of getting
lipodystrophy. Race may be of issue, as lipodystrophy has been reported to be
five times more common in Caucasians.
Protease Inhibitors and Nucleoside Reverse Transcriptase Inhibitors (NRTI'S)
have both been implicated in causing lipodystrophy, yet some people have
experienced this syndrome without ever starting this antiviral medication.
Evidence shows there is no association between the onset of lipoatrophy and
duration, initiation, continuation, and discontinuation of any antiviral
medication. Note this is true for fat loss, not accumulation. Some believe this
syndrome may be related to the interaction of the different medications.
Presentations offered many alternatives and possible explanations of
lipodystrophy.
Some studies presented at the conference tried switching classes of
medications to see if this would improve lipodystrophy. This strategy did not
seem to demonstrate any benefit at this time. It is still unclear if this
strategy is beneficial.
Further study is needed. Estimates of lipodystrophy prevalence vary, however it
is believed that up to 30% of patients develop some form of lipodystrophy.
Markers to predict who is more likely to develop it would be beneficial.
An interesting presentation was given about a cytokine called tumor necrosis
factor (TNF), which may be implicated in lipoatrophy. It appears that patient's
with lipoatrophy have abnormally high amounts of TNF. Tumor Necrosis Factor is
responsible for the destruction of injured cells, increasing the resistance to
insulin (causing diabetes), and other functions included with the inflammatory
response. Many years ago a drug called Trental, which is FDA approved for
vascular insufficiency, was used in HIV as alternative therapy because of it's
anti tumor necrosis factor ability. It fell out of fashion, however this was at
a time when there was few medications for treating HIV. Its use may be something
to consider, although I am not aware of any clinical trials looking into this.
Immune System Repair
On a good note, new studies have shown that the immune system is capable of
repairing itself with antiviral therapy. This is true even if therapy is started
when the HIV is very advanced (very low CD4 count). We used to think that immune
damage was irreversible in the advanced person. This new information certainly
has implications in determining when to initiate antiviral therapy. The old
thought was to treat early because of the inability of the immune system to
repair itself if damaged beyond a point. Now we are delaying initiation of
therapy as compared to only a few years ago. We also are discontinuing
protection, such as pneumocystitis pneumonia prophylaxis, in patients whose CD4
count has increased above 200. Caution must be taken because this immune repair
(reconstitution) happens only when therapy is successful (when the viral load
drops to near undetectable) and that does not always happen. If therapy is
unsuccessful for whatever reason (resistance, non-adherence, etc.) and
initiation of therapy is delayed, the patient will remain high risk for
opportunistic disease. Reported after 4 years of successful therapy for patients
starting therapy with CD4 counts below 50 who remained undetectable in their
viral loads, 86% had CD4 counts above 200, 61% had CD4 counts above 350, and 33%
above 500. So, CD4 increases are not limited by a low initial CD4 count. This is
very encouraging.
Drug holidays or interruption of therapy
Benefits, if any, for these still remain unclear. Newer studies have clearly
shown there is a much higher risk of disease progression if therapy is
interrupted in advanced, more compromised patients. Benefits of therapy
interruptions, if there are any, in the healthier patient still needs to be
proven. As attractive as this option sounds, sound caution is advised, and it
should probably be done only in a controlled clinical trial. For persons with
CD4 counts less than 50 the risk of an AIDS defining event in one study of
patients who did not interrupt therapy was 30%, and 80% if they went on a drug
holiday. For those with a CD4 count above 200 the risk was 5% on therapy and 20%
if they went off therapy. This provides reason for pause when considering this
treatment strategy.
Blips
Information was shared studying what effects blips (short term low level
detectable virus in a usually undetected person) have. Apparently blips are not
a predictor of pending drug failure in a drug-naïve or not heavily treated
person. Also data presented demonstrated that it is not harmful to switch out
different classes of drugs in the successfully treated patient if this is being
done because of toxicities (lipodystrophy, gastrointestinal disturbances, etc.)
New info on old drugs
There was mention of a genetic marker HLA B 57 which may predict whether one
is more susceptible to have a hypersensitivity reaction to abacavir (Ziagen).
This could be an important finding in helping make the determination of what
drugs to use in an individual patient. Before this test is recommended for use,
it needs to be determined the limitations and accuracy of this test and much
more information and studying needs be done.
Several studies have demonstrated that interleukin II is well-tolerated long
term. In addition to being well tolerated it has been used successfully to
increase CD4 cell counts. Further studies are underway to see if these CD4
increases correlate with improved health. These results, when available, should
conclude if Interleukin II is clinically beneficial.
Adherence
In an effort to improve adherence we are working towards therapeutic drug
regimens that can be taken once daily. With some effort these once-a-day
regimens can be prescribed presently. However, my personal opinion is that we
are pushing the envelope if we routinely prescribe once-a-day regimens at this
time with the medications that are currently available. It is a reasonable
option if twice-a-day dosing is not appropriate for whatever reason.
For further information on the conference, I suggest using the Internet,
particularly www.medscape.com. Also remember that scientific proof is a living
product and is constantly changing as we learn more and more. Presentations of
one's research contribute to our overall knowledge, however any result before
becoming a scientific truth, must be repeatedly reproducible. This understanding
is essential in reviewing presentations and before accepting anyone's work as
the absolute fact.
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