IAC: The Grim Days Recalled as AIDS Hits 25

TORONTO, Aug. 21 -- More than 25 years since the beginning of the AIDS epidemic, doctors, scientists and patients have grappled with how to fight human immunodeficiency virus infection -- and have learned how battle the disease to a draw.

But in the 1980s and early 1990s, the virus was way ahead, recalled Joep Lange, M.D., a professor of medicine at the Academic Medical Center in Amsterdam, The Netherlands.

"The blackest time was at the AIDS conference in Berlin in 1993," Dr. Lange said during a symposium sponsored by GlaxoSmithKline in which the quarter century of the epidemic was reviewed.

Up to then the only drug in general use to fight AIDS was Retrovir (zidovudine), or AZT, he said. "We knew that patients who took AZT did well for a while but then the virus rebounded. But it was all we had. Then came the Concorde - joint British and French trial - and it was disaster."

The trial compared patients taking Retrovir with patients not taking the drug. The result: No difference in outcome. Treated patients died at the same rate as placebo patients.

On top of that, other reports from the Berlin meeting showed no impact with sequential treatment with zalcitabine (ddC). "Patients were complaining that we were poisoning them with these drugs," Dr. Lange said. And the scientific community had no answer.

But it's always darkest before the dawn. "In 1994, the AIDS Clinical Trials Group (ACTG) study 076 was reported, and that showed that giving pregnant women AZT dramatically reduced the risk that their children would be infected at birth." In that study 30% of women not treated gave birth to HIV-positive children, but the rate was 8% if the women took AZT doing the pregnancy.

The scientific and medical community drew a collective sigh of relief. "We knew we had a good drug," Dr. Lange said. After ACTG 076, everything seemed to come into place. Combination therapy with two nucleoside reverse transcriptase inhibitors proved to be better than monotherapy, protease inhibitors reached the market and combinations of those drugs with the nucleoside analogs suddenly showed that the virus could be bludgeoned to undetectable levels. "This was pure bliss," he said.

Dr. Lange said that more importantly along came viral load testing. "Now we could see what we were doing to the virus," he said. "If we had these diagnostic tests earlier, we could have had combination therapy as early as 1992."

He said the tests would have shown that non-nucleoside reverse transcriptase drugs that were developed alongside AZT worked well, but because these drugs were so susceptible to resistant mutation they were shunted to the back burner. Today, of course, non-nucleoside-based combination therapies are the first-line standard of care.

Not everything has been golden since 1996, when a handful of new drugs were approved and AIDS patients went from their death beds and returned to their jobs. Dr. Lange noted the problem of resistance and adherence emerged, along with the perplexing problem of lipodystrophy and disfiguring fat accumulations.

By 1998, initial enthusiasm that the virus might actually be eradicated gave way to more sober realization that treatment was for the long haul. But by then, doctors had the tools to change the course of the disease and offer the hope that HIV infection could be treated like just another chronic illness.