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Being Alive

MEDICAL UPDATE: Major Announcement on ddC




 

Being Alive 1992 Feb 5: 4

In early January, the manufacturer Hoffman-LaRoche announced that it was stopping a clinical trial that compared DDC to AZT as single-agent therapy. DDC's application to the FDA is still pending. It has been available locally through the Buyers' Club and many, many people have been using it for combination therapy. DDC has also been available through an Expanded Access program run by the company, for those with proven intolerance to AZT and/or DDI or those proven to have failed on either of those drugs.

At the same time, randomized clinical trials with DDC are being conducted through the ACTG (AIDS Clinical Trials Group). One of these, ACTG Protocol 114, enrolled people with no previous AZT or other antiretroviral therapy, who have T-cell counts under 200 and who were classified as having AIDS or advanced ARC. It compared DDC (alone) to AZT (alone). Half were randomized to AZT and half to DDC in a blinded fashion.

The study's monitoring board looked at the results after one year of therapy and found that there had been 59 deaths among the 320 people on DDC compared to 33 deaths among the 315 people on AZT. Since this difference was statistically significant, it became ethically untenable to continue the trial. The blinding was broken and those on DDC were offered the option of switching to AZT.

This is clearly important information. I think many of us believed until a few months ago that DDC not only had a better toxicity profile, but that DDC might also be superior in efficacy to either AZT or DDI. This study, assuming it is borne out by further studies in differing populations, tells us that as a single agent, DDC may not work as well on average.

Two other points are equally important. First, in people who have already shown intolerance to AZT or resistance to AZT or worsening while on AZT, there's nothing wrong with trying DDC. It has not been shown to be more toxic than AZT, nor has it been shown to be ineffective just that AZT appears a bit better, for this group of symptomatic persons who had never tried either. In fact, the Expanded Access program for those who cannot take or benefit from AZT will continue and will be followed closely. (A parenthetical point here is that recent data seem to indicate that even when someone has been found to be AZT resistant and thus a candidate for switching to DDC or DDI, there still seems to be better effect with the combination perhaps lowering the AZT dose somewhat when the DDC or DDI is started rather than stopping the AZT entirely.) Second, this new finding does not apply at all to DDC's probable benefit in combination regimens with AZT. The large ACTG trial comparing AZT+DDC to AZT alone is continuing. In results of a smaller combination study presented at the Florence conference, the groups with standard or somewhat higher doses of AZT and DDC did better than the other groups. With AZT therapy alone, T-cells often rise for three to six months and then return to baseline. This study found that when DDC was combined with AZT, the T-cell rise tended to be maintained for a year or more.

So it is important not to conclude from the single-agent trial results that "DDC is no good." It is still reasonable to assume that DDC in combination with AZT is probably better than either one alone, though the scientific data are not yet sufficient to make this clear beyond a doubt. While awaiting these definitive studies, most clinicians who currently recommend combination therapy will continue to do so. 



 




Information in this article was accurate in February 5, 1992. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.