Being Alive 1995 Feb 5: 4
Last month, in my report of the top ten HIV/AIDS stories of
1994, I once again reported on my long held belief that "two
drugs generally work better than one." One Newsletter reader
challenged this statement by pointing out that there is no
proof that someone on combination therapy lives longer and
progresses more slowly than someone on only one antiviral.
While it is true that no survival benefit has been
definitively established, there seems to me enough evidence
to date to suggest that combination therapy is a reasonable
alternative to monotherapy and just may provide greater
The early studies of combination antivirals were all done in
the test tube. These in vitro studies showed that a
combination of drugs was indeed more powerful in slowing HIV
replication than was a single antiviral. In 1992, data from
an in vivo study, ACTG 106, were released. This large study
looked at six different combinations of AZT and ddC, and did
show a T-cell advantage in people who were taking both drugs.
Unfortunately, there was no long-term follow up, and so we do
not have survival data. One of the big unanswered questions
about HIV therapy is whether increased T-cell counts
translate to longer survival. Intuitively we think so, but we
have to date no proof.
In 1993, researchers presented the data from ACTG 155. This
study was the first to look at clinical endpoints in
combination therapy. For those in the study with a CD4 count
less than 150, there was no difference in outcome whether on
combination therapy or monotherapy. For those with a CD4
count between 150 and 300, there was a non-statistically
significant difference in improved survival for those on
combination therapy. Some would argue that this
non-statistically significant difference points to a possible
trend and that with people whose CD4 count was above 300, we
might indeed establish that combination therapy offers a
survival benefit. Unfortunately, we do not have such data
from ACTG 155.
A more recent ACTG study, ACTG 229, demonstrated that a three
drug combination provided greater viral suppression and
higher T-cell rise than did monotherapy. Again, we do not
have follow up data to determine long term benefit.
So where is the proof that combination antiviral therapy is
ultimately more efficacious than monotherapy? For some, the
studies that show increased T-cells and decreased viral load
are enough. For others, since no survival advantage has been
definitely established, the proof is lacking. As with so much
of this disease, one needs to review the available data and
make reasonable choices. In that light, it seems to me that
we can say that two drugs, all else being equal, generally
work better than one.