AIDS TREATMENT NEWS #226, July 7, 1995
The interview with Dr. Margaret Poscher, below, is the first
in a series of articles and interviews on combination
anti-HIV treatment. For over a year, it has been almost a
cliche that combination treatment is the wave of the future;
however, the actual data on how well drug combinations work
in people has been, and still remains, minimal and
disappointing. But new information has recently renewed our
interest in this potential advance:
* Laboratory studies are showing that some combinations work
much better -- or much worse -- than might have been
predicted, in suppressing HIV in laboratory cultures.
Some of these studies have been conducted over the last five
years by Marty St. Clair, Ph.D., of Burroughs-Wellcome (now
Glaxo Wellcome). Among the few drugs that she has tested so
far, she has found that certain triple combinations work
best. Some of the best results have been with AZT, plus
either ddI or ddC, plus either 3TC or nevirapine.
These laboratory studies have also suggested that it is
better to combine drugs than to alternate them. Also, it is
usually best to begin the different drugs at or close to the
same time, if possible; the combinations may be less
effective if the patient has already been using one of them
for months or years, allowing resistance to develop. And the
laboratory tests suggest that these combinations may be most
active when the viral concentration is low, suggesting that
they may work better in early stage HIV infection, than in
Conditions in the human body, of course, are very different
than in laboratory cultures. Therefore this laboratory work
can only provide guidance or suggestions as to what
combinations may be likely to work. Only human trials can
tell whether or not a particular regimen is truly promising.
Dr. St. Clair presented a preliminary report on this
laboratory work last January at the 2nd National Conference
on Human Retroviruses and Related Infections, in Washington,
D. C. A full report will be published soon.
* Recently we heard about a case of very successful use of
one of the combinations suggested by the laboratory work
(AZT plus 3TC plus ddC), by a person we know. His CD4
(T-helper) count was 300 a year ago, then declined rapidly
to 110 last November 1, and to 70 last December 1, when he
started the triple combination treatment. In February his
count was 320, and in March it was 540. In April he had a
bad case of flu, and his count dropped to 420. Then it
went up to 450, and in June 1995 was 480.
In November he had hairy leukoplakia, bad thrush, and bad
scalp lesions; he had lost weight and was sleeping up to 18
to 20 hours a day. Now all symptoms are gone, and he has
gained 25 pounds and is sleeping normally. He appears to be
in perfect health.
This person, importantly, was treatment naive when he started
the triple combination. He used standard doses of the drugs,
but sometimes reduced the AZT dose from 500 mg to 400 or 300,
due to stomach upset. He was using no other treatment at the
time except for acyclovir.
Certainly no single case can prove that a treatment works;
and we suspect that few people will find equally good results
from this combination. But still cases like this compel
attention, since comparable results are never seen with
conventional HIV treatment. We mentioned this experience
because it suggests a possibility, a goal, worth aiming for.
Also, it suggests designs for clinical trials; for example,
if a patient has a CD4 count below 50 and has CMV retinitis,
and combination HIV therapy raises the CD4 count to a level
where CMV is not normally a risk, will the retinitis stop
progressing, thus reducing or eliminating the need for
specific CMV treatment?
* On June 30, Glaxo Wellcome applied to the FDA for
accelerated approval for 3TC, for use in combination with
AZT as first-line treatment for adults with CD4 counts
under 500, and for children who meet the CDC guidelines for
treatment with antiretrovirals. If the drug is approved
for this indication, it will probably make combination
treatment the standard of care for many (though not all)
persons under 500, making it much easier to get this
treatment paid for. It will also encourage experimentation
with three-drug combinations, as approved drugs like ddI or
ddC are added to the regimen.
Today, combination antiretroviral treatment, especially
triple combinations, are more talked about than used. As we
asked around for referrals to physicians who might have
experience with triple combinations, the same names kept
coming up again and again. Most of them have only used
triple combinations with a few patients. And they have
different approaches to when and how they use these
treatments; consensus has not yet developed. This slow start
for combination treatment is not surprising, due to the lack
of definitive data from clinical trials.
The interviews in this series will examine some of the
different approaches which are in use, and why physicians
make the choices they do. Note that these interviews will
focus primarily but not only on combination treatment; they
will also look at related medical topics when they arise.