Lipoatrophy and
Antiretroviral Drug Changes
by John S. James, AIDS Treatment
News
Lipoatrophy is abnormal fat loss, often
seen especially in
the face, arms, and legs. Sometimes fat inside the abdomen
(a
different kind of fat) will increase at the same time the
fat
underneath the skin is disappearing. It is believed that
lipoatrophy is caused primarily by antiretrovirals --
although there are different views on
whether some protease
inhibitors, some nucleoside analogs, or the combination
of
both is most responsible. Doctors have noted that usually the
lost fat
is not quickly regained even if the antiretrovirals
are stopped. Many patients are distressed
especially by the
loss of facial fat.
The Retroviruses conference
included some reports on partial
success in managing lipoatrophy with certain drug changes.
(See note below on
additional information available online.)
* [Abstract 32] Patients with
moderate or severe lipoatrophy
who were taking
either d4T (Zerit(R)) or AZT (Retrovir(R))
were randomly
assigned to either continue their treatment, or
substitute abacavir (Ziagen(R)) for the d4T
or AZT. This
research team, including leading lipodystrophy
researchers
Carr and Cooper in
patients. Careful high-tech measurements of limb fat (using
either
DEXA or CT) found an improvement in lipoatrophy in
the
group that switched to abacavir, but not the
group that
continued on their d4T or AZT, in the six months of this
trial.
The lost fat returned slowly, however -- patients did
not change their
average rating of their own lipoatrophy in
the six
months of this trial. And researchers estimated that
at the rate of change
which was measured, it would take
several years for the lipoatrophy to disappear.(1)
The patients in this
study started with a high CD4 count
(average 577), and a viral load that was
stable at under 400
copies with the regimen they were on. Eighty four percent
of
them had been taking d4T, 16% had been taking AZT.
The switch to
abacavir also resulted in a decline in lactate
(a good sign), and a modest decline in viral load
of 0.25
logs.
Other Lipoatrophy Studies at
the Retroviruses Conference
Two Glaxo-supported
studies also reported some measurable
improvement in lipoatrophy -- with switches that were
entirely to Glaxo drugs:
* [Abstract 701-T] A team at several
U.S. universities found
improvements in lipoatrophy
when d4T was replaced by either
AZT or abacavir. Of
118 volunteers enrolled, 86 switched to
abacavir,
the others to AZT (as Combivir). Lipoatrophy
improvement was found at 24 weeks. The study
will run for a
total of 48 weeks.(2)
Note that this study and the one
above are similar in one
respect, that both switched most of the volunteers
from d4T
to abacavir (except of course for the
control group in the
Australian study, which did not switch at all).
*
[Abstract 700-T] A team in Perth, Australia reported
considerable success
with lipoatrophy at 48 weeks, in a
controlled trial
in which volunteers were randomly assigned
to either switch from d4T and/or a
protease inhibitor to AZT
+ 3TC + abacavir, or not
to switch their therapy. Those who
switched did better than those who did
not.(3)
* [Abstract 684a-T] Another study found
a seemingly very
different result. A group of 337 patients who did NOT
have
any signs of lipoatrophy were studied 21
months later; 13.1%
of them (44/337) had developed moderate or
severe
lipoatrophy. The risk factors were white
race, and severity
of disease. When the statistics were
adjusted for HIV disease
severity, "there appeared to be little, if any,
effect of any
antiretroviral agent or class of agents on the development
of
lipoatrophy."(4)
We do not know why this study did not find an
association
between development of lipoatrophy and
particular
antiretrovirals, while the three studies
above had found that
switching antiretrovirals
could to some degree reverse
lipoatrophy which had
developed on the original treatment
regimen (which would imply that some
regimens are more
responsible than others for the development of
this
condition).
* [Abstract LB13] Rosiglitazone, a diabetes drug which
increases
subcutaneous fat in patients with type 2 diabetes,
did not significantly increase subcutaneous fat in a
24-week
trial with 15 HIV patients with lipoatrophy
who were on the
drug, compared to 15 controls.(5)
* [Abstract 704-T] A
cosmetic treatment for facial
lipoatrophy --
injections with polylactic acid (NewFill) --
was reported for 16 patients, 14 men and 2
women, by
physicians in Paris. The doctors reported that the treatment
was
"safe, convenient, and effective" in those patients.(6)
Comment: Caution on Switching Drugs
There
are many factors to consider in switching
antiretroviral regimens. This
decision should be made with
the help of an experienced HIV physician -- who
might want to
change other drugs in the regimen to improve
antiviral
activity or mitigate other side effects, or to make the
regimen
easier to use. Abacavir may not be the best drug
for
the particular patient (it just happened to be studied more
and
reported at this conference). And if abacavir is
used,
the patient and physician must be alert to
the
hypersensitivity reaction which occurs in about 5% of
patients; if
this happens, the abacavir must be stopped
and
NEVER started again.
But lipoatrophy is
not just a cosmetic problem; it is a sign
that the drug regimen may be
causing serious side effects. If
the regimen is not changed, the problem is
likely to get
worse. One possible strategy is to act once it is clear
that
lipoatrophy is starting, and look for an
antiretroviral
regimen that has been shown to stop or slowly reverse
this
condition after it has started, in many patients.
For background
and cautions on changing therapy, see the
following articles on the lipoatrophy information presented
at this Retroviruses
conference:
"Switching Antiretroviral Therapy for Lipoatrophy," by David
Alain Wohl, M.D., at:
http://www.natap.org/
(look for the 9th
Conference on Retroviruses and
Opportunistic Infections report).
Also
see "Switching Therapy to Manage Lipoatrophy:
More
Evidence of Limited Benefits," by Graeme Moyle, M.D.,
M.B.B.S., at:
http://www.medscape.com/viewarticle/429162
(If
this is your first time using the Medscape site, you
will
need to sign up for a free registration in order to read
this
article.)
References
1. Carr A,
Smith D, Workman C, Hoy J, Doong N, Amin J, Law M,
Cooper DA, and the MITOX Study Group.
Switching stavudine or
zidovudine to abacavir for HIV
lipoatrophy: A randomized,
controlled, open-label, multicentre, 24-week study. 9th
Conference on
Retroviruses and Opportunistic Infections,
2. McComsey G, Lonergan T, Fisher R and others. Improvements
in lipoatrophy (LA) are observed after 24 weeks when
stavudine (d4T) is replaced by either abacavir (ABC) or
zidovudine
(ZDV). 9th Conference on Retroviruses and
Opportunistic
Infections,
[abstract
#701-T].
3. John M, James I, McKinnon E, and others. A
randomized,
controlled open-label study of revision
of antiretroviral
regimens containing stavudine
(d4T) and/or a protease
inhibitor (PI) to zidovudine (ZVD)/lamivudine(3TC)/Abacavir
(ABC)
to prevent or reverse lipoatrophy: 48-week data.
9th
Conference on Retroviruses and Opportunistic Infections,
4. Lichtenstein K, Delaney K, Ward D, Moorman A, Wood
K, and
Holmberg S. Incidence and risk factors for lipoatrophy
(abnormal fat loss) in ambulatory
HIV-1-infected patients.
9th Conference on Retroviruses and Opportunistic
Infections,
5. Sutinen J, Hakkinen AM, Westerbacka J and
others.
Rosiglitazone in the treatment of
HAART-associated
lipodystrophy (HAL): A randomized, double-blind,
placebo-
controlled trial. 9th Conference on Retroviruses
and
Opportunistic Infections,
[abstract
#LB13].
6. Lafaurie M, Dolivo J, Boulu D, Madelaine I, and Molina JM.
Treatment
of HIV-associated lipoatrophy of the face
with
intradermal injections of polylactic acid. 9th Conference
on
Retroviruses and Opportunistic Infections,
22-28, 2002
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