The ever fragile optimism of treatment activists strained to the breaking point in late 1991. The second generation of antiviral AIDS drugs—the non-nucleoside reverse-transcriptase inhibitors that had been engineered specifically to fight HIV and that had looked so promising in vitro—performed poorly in clinical trials. Merck's "L" drugs, nevirapine, and another drug called TIBO were all shown to have little individual efficacy against the virus because the viral gene that produced reverse transcriptase proved capable of mutating in a matter of days or weeks to resist these compounds. For some time now, the avowed goal had been to use the little-loved nucleoside analogues, AZT, ddC, and ddI, to keep people alive just long enough to get better drugs into circulation. Now people would have to depend on the first-generation drugs for much longer—while those who ceased benefiting from them would have no obvious therapeutic recourse standing between them and complete immune collapse.
The news about the non-nucleoside reverse-transcriptase inhibitors "was nothing short of shattering," said Theo Smart of ACT UP/New York. "So many hopes had been pinned to [these drugs'] effectiveness." "Researchers openly wondered, 'What are we going to do next?'" reported Jesse Dobson of ACT UP/Golden Gate and the Community Constituency Group, describing an ACTG meeting in late
1991. "Activists Despondent and the Movement Is Splintering" was the headline of one of a series of articles in the San Francisco Examiner by reporter Jayne Garrison, describing the state of affairs. Garrison quoted Peter Staley, a prominent New York activist: "As far as I'm concerned I'm going to die, Magic Johnson is going to die and the million Americans who are presently infected will die." Concluded Garrison: "So far, the virus is outsmarting science."
Martin Delaney, projecting the generally upbeat message of Project Inform, rejected the "gloom and doom" and stressed instead the continued importance of combination therapy with nucleoside analogues, the apparently large numbers of "long-term survivors" who had been living with HIV for a decade or more, and the promised protease inhibitors and tat inhibitors then on the horizon. Unfortunately, the ongoing saga of Hoffman-LaRoche's tat inhibitor—the only such drug in development—was hardly reassuring. For reasons that were inexplicable to the Johns Hopkins researchers who had been contracted to conduct the study, the company summarily postponed its Phase I trial in May 1991. Activists had generally found this company less cooperative than most; now they could only speculate that Hoffman-LaRoche wished to avoid subsidizing another parallel track program, having given out free ddC to more than three thousand AIDS patients.
At first the company announced that it would sell its tat inhibitor to the highest bidder; then, half a year later, Hoffman-LaRoche changed its mind, saying it would develop the drug after all. "Apparently the company decided that this drug was too good to sell—especially in view of the disappointing results with the competing class of non-nucleoside reverse-transcriptase inhibitors," suggested John James in AIDS Treatment News . But throughout 1992, Hoffman-LaRoche sat tight. In early 1993 activists declared open warfare on the company with the mass resignation of the members of the Community Advisory Board that the company had established. "There can be no more polite dialogue with your company," said TAG and ACT UP/New York in a letter sent to Hoffman-LaRoche in late January threatening a boycott of its products, laboratories, and home care services. In his column in the Advocate , Delaney proposed that the government seize the drug "in the national interest": "Eminent domain is frequently used to seize private property for such national emergencies as highway construction. Is AIDS less important?"
As John James observed, the lesson of the tat inhibitor extended
well beyond the cupidity or irresponsibility of a single company. Here was a type of drug that "leading AIDS scientists" considered to be "perhaps the single most promising approach to developing better AIDS treatments"; furthermore, potential tat inhibitors could easily be discovered through known screening methods. There was no reason, in theory, why there couldn't be fifty tat inhibitors in development; "instead, the whole pharmaceutical industry (or rather, that small part of it which has any interest in AIDS) seems to be waiting to see what happens with the only tat inhibitor drug now in human testing. …" It was a maddening picture: "In the middle of a major worldwide epidemic, the most promising approach to treatment development has been abandoned to a single project with a single drug in a single company." The problem was not just Hoffman-LaRoche; the problem was the whole notion that the "invisible hand" of the free market would somehow function in the service of the public good and not just private gain—a notion that the NIH was unwilling or unable to challenge. And, separate from the issue of political economy, there remained the additional, nagging question: Why did Hoffman-LaRoche seem to have "so little interest in its own drug"? "What might it know that we don't?" asked James.