PI Perspective 21: ACTG 320: Last of the Body Count Trials?

Important note: Information in this article was accurate in March, 1997. The state of the art may have changed since the publication date.

PI Perspective 21: ACTG 320: Last of the Body Count Trials?

Project Inform - March, 1997

In what was hopefully the last trial of its type, ACTG 320 was halted early when one of its treatment regimens proved clearly superior to the other. The study concluded that when people with advanced disease and a prior history of antiviral treatment received either AZT + 3TC or AZT + 3TC + indinavir (Crixivan, the Merck protease inhibitor), those who received the 3-drug combination fared better in every way. They lived longer and were less likely to progress to AIDS, at no cost in increased toxicity. The triple therapy resulted in about a 50% reduction in death and progression to AIDS-defining infections over an average 38-week followup time. The study was stopped earlier than planned when analysis showed the advantage for the 3-drug regimen. All 1156 participants started with CD4+ cell counts under 200, (average CD4+ cell count was 89) and 38% had CD4+ cell counts below 50. Eighty-three percent were male, 17% female, 27% black, 19% Latino and all had prior antiviral experience but were new to 3TC and indinavir. Results are shown in Table 1.

**Table 1: ACTG 320**
		AIDS or death			Death
	All	<50 CD4+	<50 CD4+	All	<50 CD4+	<50 CD4+
AZT+3TC	63 (18%)	44 (34%)	19 (9%)	18 (5%)	13 (9%)	5 (2%)
AZT+3TC+ indinavir	33 (9%)	23 (16%)	10 (4%)	8 (2%)	5 (3%)	3 (1%)

Ethical and Scientific Concerns

The outcome of this study surprised no one, since at the time it was initiated, other studies had already shown the superiority of the 3-drug regimen compared to 2-drug nucleoside combinations. The people receiving the 2-drug regimen were, in the view of many, doomed to an inferior outcome. The question is: why was such a study done? Many activists, researchers, physicians and even employees of the companies involved protested bitterly from the outset that this study would result in an earlier and higher death rate for those receiving AZT + 3TC. Supporters of the study, mostly the FDA and a few medical conservatives who somehow got their way, argued that the clinical and survival benefits of the 3-drug combination had not yet been proven in a randomized, controlled clinical trial. Technically, this is true, but irrelevant to anyone except those who refused to acknowledge earlier studies showing that the triple combination produced dramatically better and longer-lasting reductions in viral load and improved CD4+ counts. Other studies had already shown that improvements of this type were directly associated with major improvements in survival and delayed progression. Unable or unwilling to put the two types of studies together and draw reasonable conclusions, the study’s supporters pressed their demand for a body count before they would accept what had become obvious. In the end, the trial was halted when volunteers began leaving in droves and researchers were having nightly pangs of conscience as they saw the body count rise. A hastily called analysis reaffirmed what was already known about the superiority of the triple therapy and the study was halted, albeit with an excess of dead bodies and people who had progressed to AIDS.

Some of the brave but unwitting volunteers who participated paid the price with their lives, while others are left with perhaps irreversible immune suppression. In their honor, we must be certain that neither the FDA’s traditions nor the doubts of scientists who cannot reason will ever again be valued over lives of people. The time for studies whose outcome is measured in bodies is over in this epidemic. It has long been over.

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Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1997. AEGiS.