GMHC Treatment Issues 1995 Oct 10; 9(10): 3
Some activists and researchers have heralded the findings of
ACTG 175 and Delta as "the most important trial results ever."
Much time already has been spent pouring over the studies'
statistics, comparing populations, and drop-out rates in a
valiant attempt to understand what these studies mean. What it
all boils down to is that AZT monotherapy is not the best
treatment available, whether as initial therapy or in the
drug-experienced. This finding does not impress some. "Treating
clinicians have known this for years," said Stacy Kreiswirth, a
nurse practitioner from New York attending ICAAC, "show me
something that will help my patients."
It is hard indeed to get excited about ddI and ddC, drugs that
have been around for so long and that clearly do so little, as
evidenced by Delta II, in which more than a quarter of the
participants had died by the end of the two- year study,
regardless of the treatment received. These studies' findings
do little to expand people's treatment options.
Some of these studies' findings are counter-intuitive. Why
didn't AZT/ddI fare better in delaying disease progression or
death than ddI alone? In the experienced population this may
have been due to AZT resistance, but in the naive population,
one would expect to have seen at least a trend in favor of the
combinations AZT/ddI and AZT/ddC. Both did have a more
pronounced effect on viral load than ddI in these patients, as
reported by Daniel Kuritzkes, M.D. (ICAAC abstract LB-02), but
in the experienced patients AZT/ddC performed substantially
worse clinically than ddI. ACTG 175 appears to call into
question the clinical utility of viral load tests.
Delta II, which is still continuing, found no difference
between combination and monotherapy in antiretroviral
experienced people, and so contradicts the findings of ACTG
175. The participants in Delta II were at a much later stage of
disease, though, so comparisons are difficult. There also could
have been more resistance to AZT, which could decrease the
benefit received from treatment with ddI or ddC (see page 14).
The findings of these studies may become quickly irrelevant
because of new and more potent drugs being added to the
therapeutic arsenal. Where will d4T or 3TC fit into the
picture? Certainly, AZT/3TC is a much more potent combination,
although we have little clinical information. Glaxo-Welcome has
requested approval for AZT/3TC as first- line treatment.
Meanwhile, test tube data suggests that virus resistant to 3TC
is less susceptible to ddI and ddC. How should this effect
treatment decisions? Also, clinical data on the protease
inhibitors will soon become available. Treatment options are
increasing, but when to employ which regimen is affected by
such issues as cross-resistance, synergy and toxicity. Without
the clinical data, it is impossible to know which variable is
more important in making treatment decisions.
Finally, neither study provides information about the optimal
time to start therapy or when to switch regimens, and there are
no studies currently underway that will answer these questions
soon. ACTG 175 and Delta did yield some precious, though
somewhat contradictory data on clinical benefit. How to apply
the lessons learned beyond the particular populations and
regimens under study remains a mystery.