No survival bonus from early AZT.

Magic Johnson's performance in all National Basketball Association's All-Star game proved that people infected with the AIDS-causing virus, HIV, can compete -- and compete spectacularly. This week, however, a new scientific study lessens some of the magic associated with zidovudine (AZT), the mainstay antiviral drug used to fight HIV.

Back in 1989, a study revealed that early zidovudine treatment slowed progression to AIDS in outwardly healthy people infected with HIV (SN: 8/26/89, p.135). That report and others held out the promise that HIV-infected people would live longer if they took the drug at the start of the disease process, well before the devastating symptoms of AIDS emerged.

A report in the Feb. 13 NEW ENGLAND JOURNAL OF MEDICINE confirms that AZT can slow progression to AIDS but dashes the hope that such early treatment can prolong life. "While AZT is clearly a benefit, it's not the ultimate answer," says principal investigator Michael S. Simberkoff of the Veterans Affairs Medical Center in New York City.

Simberkoff and his colleagues at VA Medical Centers across the country set out to study the benefits of early zidovudine therapy in 338 people who did not suffer full-blown AIDS but who did exhibit mild signs of HIV infection, such as night sweats, diarrhea and unexplained weight loss. The recruits also showed immune system damage by HIV: All had CD4-lymphocyte counts of between 200 and 500 cells per cubic millimeter of blood. Healthy people have CD4 counts of 800 to 1,200.

The VA team randomly assigned 170 people to a group that received zidovudine right away. The remaining 168 participants got placebo pills at the study's start but received the drug when AIDS developed or their CD4 counts dropped below 200.

After approximately two years of observation, the VA researchers discovered that early zidovudine therapy slowed the rate of development of AIDS by nearly half. Once AIDS appeared, however, the early therapy group developed multiple opportunistic infections and died quickly: The team reports 23 deaths in the early therapy group compared with 20 deaths in the later treatment group. Thus, the study revealed no survival bonus for those who got early treatment.

The VA researchers admit they don't know why zidovudine failed the long-term survival test. Simberkoff speculates that some people who take the drug early may develop resistance to it.

Many studies have shown that zidovudine gives people with full-blown AIDS a survival edge, but up until now research has not focused on the question of whether zidovudine would prolong life if taken early in the disease process. The VA study provides desperately needed data on early zidovudine treatment.

For generally healthy HIV-infected people, a decision to hold off on zidovudine therapy can make sense, asserts John D. Hamilton of the VA Medical Center in Durham, N.C. Hamilton, also a principal investigator of the VA study, notes that early zidovudine provides no survival benefit, remains costly and can trigger severe side effects such as nausea and vomiting.

On the other hand, Lawrence Corey of the University of Washington in Seattle notes that early zidovudine therapy delays progression to AIDS -- a benefit that outweighs any later ill-effects of early treatment, he believes. Corey wrote an editorial accompanying the research report.

Simberkoff is also in favor of early treatment. "Our first job is to prevent the onset of illness," he says. Patients who show signs of resistance to zidovudine can switch to another antiviral drug such as dideoxyinosine, he adds. In his editorial, Corey adds that researchers need more information on whether this strategy actually will prolong life.

In February 1991, FDA heard preliminary results of the VA study and decided against any change in zidovudine availability, which is now approved for people with AIDS and for those with early HIV infection.