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T
REASONS FOR HOPE
The g rea t d eb ate
he latest and perhaps best advice from
many leading researchers who spe
cialize in the field of HIV treatment is
to “hit hard, hit early.” This means
“Hit hard, hit early,” or wait until more data comes in about
tightly controlling HIV as soon as
possible by taking combinations of antivirals that
the new drugs and their long-term effects?
drive down the amount of virus in the blood to
▼
undetectable levels.
There are sound arguments behind this recom
by The Boston AIDS Writers Group
mendation, but many practicing physicians and
people living with HIV disease remain hesitant.
There would be no debate if there were an antivi
ral that always worked to stop HIV and had no
side effects. But so far, every combination has had
side effects and limitations whose long-term im
plications are unknown.
Hence the debate: Should people follow the
new advice and hit the virus as hard as possible
immediately with the drugs now available, or
follow a less stringent course while waiting for
more information and better drugs?
Many studies show that most people can now
reduce the amount of HIV in their bloodstream
(viral load) to levels that are not detectable by
current tests. Should doctors and people with HIV
do anything they can to achieve this effect? For
people with full-blown AIDS, the answer is an
emphatic yes. This is the only strategy that can
H olding S omething in
H itting H ard :
lengthen lives and ward off opportunistic infec
tions. Unfortunately, not everyone with AIDS
R eserve : F or and A gainst
T he R ules to F ollow
can get their viral load low enough, given the drug
There is no doubt that some people feel afraid
The hit hard approach can involve some risks.
options presently available. For this population,
to use the most powerful antiviral combinations,
It reduces viral load to undetectable levels about
hope depends on the ever more powerful combi
leaving nothing in reserve if they don’t work.
60 percent to 90 percent of the time, but there are
nations now being developed.
One reason for waiting to use a hard-hitting
no clear options for people for whom it does not
On the other hand, there are people with HIV
work.
An
aggressive
treatment
regimen
can
be
combination
is that it is unknown whether the use
where the “hit hard, hit early” approach is only
of these drugs forecloses future options. It is
like putting all your eggs in one basket. If it does
one of several possibilities. The latest antiviral
possible that using a particular antiviral now, for
not
keep
viral
load
in
check,
for
whatever
reason,
combinations are impressive, but they have a
example, will take away the option of using others
it may take away the chance to use these kinds of
limited track record. Soon much more will be
later (perhaps even those not yet available). Wait
drugs,
and
perhaps
even
some
other
antivirals,
known about the growing array of drugs in the
ing for more information before using a very
later. The very reason that hitting hard is impor
pipeline, so for some people it might be a good
powerful combination might be a wise choice.
tant,
which
is
to
prolong
the
drugs’
effectiveness,
idea to forestall treatment.
However, this strategy of holding something in
implies that if it fails, future options may be lost.
Regardless of health status, it is essential for
reserve
has one rule you may want to follow.
This fact leads to two very important rules for
people living with HIV to begin wrestling with
Decide what hit hard combination (usually in
how to hit hard.
treatment decisions, taking into account the central
volving a protease inhibitor), will be held in
First, if you are on an antiviral or a combina
considerations: “What should I take and when?”
reserve. Then pick a combination for immediate
tion that may not be working, do not just add
use, one which has a chance to get viral load down
another medication (say a protease inhibitor) on
H itting H ard :
to undetectable levels, but which does not de
top of your current regimen. If the old drugs are no
crease the likelihood that the hit hard combination
longer effective then only the new drug is actually
T he A rgument in F avor
will still be effective when needed.
working. A single drug, as explained above, will
Clearly, holding something in reserve is not a
probably stay effective for only a limited amount
The human immunodeficiency virus makes
choice everyone can make. Many people have used
of time before a resistant strain emerges. Instead
billions of copies every day, and many of them are
up so many antivirals that there are practically no
of just adding a new drug, work with your doctor
mutations. It is likely that a mutant strain of the
options left except one hit hard combination. But
to find a new combination that is likely, given
virus will eventually become resistant to avail
some people, especially those who have never used
your antiviral history, to get your viral load down.
able antivirals when taken alone (what is known
antivirals, may have a chance to get two bites at the
Second, take these combinations according to
as monotherapy). In order to delay resistance,
apple. For example, the antiviral ddl plus a cancer
schedule. With hard-hitting combinations, the
antivirals are now used in combinations. “Hit
drug called hydroxyurea, or the antiviral combina
whole idea is to keep viral load down to undetect
hard” is an effort to knock down HIV to levels that
tion of ddl plus d4T, can reduce viral load to
able levels all the time, in order to avoid drug
cannot be detected by the most sensitive viral load
undetectable levels for some people, leaving the
resistance. It cannot be overemphasized that miss
tests. (Use a test that measures the lowest possible
triple
combination AZT and 3TC plus a protease
ing
doses
can
cause
treatments
to
fail.
viral load. The most sensitive tests available mea
sure the virus down to 400 or 500 copies per
milliliter, and better, more sensitive, tests should
meet.
be available next year.)
C
orrective
action
taken
First, all o f the results of the remaining
The good news is that hitting hard usually
backlogged specimens were to be returned to
works, and works well. Effective use of drug
on R oche viral load
physicians by Dec. 14. Second, for each indi
combinations can reduce viral load to undetect
vidual who had a specimen that was not pro
able levels in most people and, it is believed, will
ACCESS PROGRAM
cessed by mid-October, Roche will offer two
stop further damage to the immune system. There
coupons for future free tests, valid for six
This summer this column and other treat
is evidence that people who experience dramatic
months. In order to avoid a similar backlog,
ment information sources announced that
reductions in viral load usually get a significant
these free vouchers will go out over a period
Roche Diagnostic Systems was offering two
increase in T cells and fewer opportunistic infec
from mid-December 19% to the end of March
free viral load tests between June 17 and Aug.
tions than those who use other, less aggressive,
1997. If your test did not come back in time, be
16. While about 56,000 specimens were pro
treatment regimens.
sure to contact your physician and have him or
cessed, Roche had miscalculated willingness
Such an aggressive treatment strategy has
her order your free coupons when they hear
on the part of laboratories to take part. This
added long-term benefits as well. Maintaining a
back from Roche. This is especially important
meant that some 24,000 specimens still had
low viral load can avoid the problem of drug
because
physicians will have to check their
not been processed by mid-October. Clearly
resistance. HIV can only become resistant to the
own records to see whose test is coming back
this was a problem for people making crucial
combination of drugs when it is reproducing in
late, as the tests are sent back with codes, not
treatment decisions on the basis of these tests.
large numbers and mutating. Therefore, reducing
names, to ensure confidentiality.
While it will not undo past damage, it is
viral load to extremely low levels, which means
heartening to see Roche make new commit
HIV is not reproducing rapidly, should make sure
The Boston AIDS Writers G roup
ments, which it is hoped they will be able to
the drugs will remain effective longer—perhaps
indefinitely.
T
inhibitor still available for later. But for those who
have already used many drugs, or whose Tcells are
so low that they should not wait, hitting very hard
right now is the best option.
Soon nearly everyone may have more than one
hard hitting way to get their viral load to undetect
able levels; most people will then be able to have
their antiviral cake and eat it too.
W hen to B egin :
T he “ H it E arly ” D ebate
For people with AIDS, or with high levels of
virus in their blood (over 20,000 or 30,000 cop
ies), or with fewer than 300 T cells, there is no
question on when to begin hitting hard: now.
For everyone else, the decision depends on many
factors. There are a number of arguments for wait
ing. One is that in time, we will know more about
available treatments. This is a sensible view for
people with not much damage to their immune
system (especially for people with Tcellsover about
700, not dropping quickly, and low viral loads).
A second argument is that if you are currently
healthy, taking strong combinations, which usu
ally involves taking lots of pills, may make you
feel worse due to side effects. This loss of quality
of life may be a factor in deciding to wait.
Another argument for waiting acknowledges
that if a powerful drug combination fails, there
may not be a good combination available later,
when it is really needed. On the other hand, some
would choose not to wait, counting on the devel
opment of other effective combinations and new
drugs now being studied.
And perhaps the most important argument for
waiting is that it is still too early to know the long-
range effects of taking hard-hitting combinations
for many years.
The major argument for not waiting is simple:
While you wait your immune system could con
tinue to deteriorate. As yet there is no sure-fire
way to restore immune function. It appears that
the less damage there is, the easier it will be to
restore what has been lost. In addition, if you wait
too long, your viral load could reach levels from
which it would be difficult to lower it back down
to undetectable levels. Keep in mind that people
with higher viral load have a more difficult time
getting HIV under control. Hitting hard is the best
way to avoid resistance and prolong the useful
ness of the antiviral drugs.
While the Boston AIDS Writers Group be
lieves that if you use antivirals it should be with
the goal of getting your viral load to undetectable
levels, the decision on when to hit hard is more
difficult. It involves many factors such as what
drugs have already been used, T cell count (and
whether or not it is falling quickly), viral load, and
perhaps most important, whether you will stick to
a hard-hitting regimen once you begin. This diffi
cult decision is best made on an individual basis
with the help of a doctor who knows the latest
treatments and understands how best to use them.
Of course the truly good news is that we can
even have this debate. Until recently no one knew
how to get HIV infection under tight control. The
fact that we can now choose to hit hard at all is the
best reason for hope yet.
The Boston AIDS Writers Group consists o f
Robert Folan and Lou Pesce o f ACT UP-
Boston; and David Scondras, Robert Krebs,
Derek Libby and Larry Bresslour from Search
fo r a Cure. Search fo r a Cure, a nonprofit HIV
treatment and education organization,
coordinates the writers group and also
organizes the ALERT network, which helps the
HIV-affected community to impact on
treatment and research issues. For more
information contact Search fo r a Cure, 58
Burbank St., Boston, MA 02115; phone
(617) 536-2474; fa x (617) 266-0051; or e-mail
cslp @ search-cure. org.