CURRENT DRUGS NO MATCH FOR AIDS EPIDEMIC

By Mike Smith

Biotechnology Newswatch 17 July 2000

There's no hope for a cure for AIDS with current drugs, the head of the National Institute of Allergy and Infectious Diseases (NIAID) said at the 13th International AIDS Conference. ''Eradication is not possible,'' Anthony Fauci said.

That means, Fauci said, that researchers must find ways of making current drug therapies work better, at a lower cost in price and side effects. One possible approach, he said, is to interrupt therapy for short periods of time.

Fauci presented preliminary data on NIAID trials of various types of interrupted therapy, but cautioned that physicians shouldn't leap to the conclusion that it works: The jury is still out, he said, although the early data are promising.

Mark Wainberg of McGill University, president of the International AIDS Society, said the idea is ''enormously risky'' but if it works would be a good way to overcome some of the obstacles to HAART.

Especially, he said, such therapy would be cheaper and would be more accessible to HIV-positive people in poorer countries.

The conference was overshadowed by the politics of HIV, sparked by South African President Thabo Mbeki's well-publicized questioning that the virus causes AIDS. AIDS researchers were hoping that Mbeki would use his keynote speech at the opening of the conference to say that he is now convinced of the etiology of the virus, and would commit his government to attacking HIV.

Instead, Mbeki said the health problems of South Africa can be blamed on poverty, and can't be laid at the feet of ''a single virus.''

Researchers and AIDS activists were predictably unhappy. South African judge Edwin Cameron, who is HIV-positive, blasted Mbeki for his ''flirtation with those who in the face of all reason and evidence have sought to dispute the etiology of AIDS.''

Unlike other meetings, this conference was largely free of demonstrations.

It was interrupted briefly July 11 by piercing whistles and airhorns wielded by about 20 demonstrators from the AIDS activist group ACTUP. The demonstrators, chanting ''Greed costs lives, pills cost pennies,'' were protesting the lack of affordable drugs in the developing world.

The protest was the first non-sanctioned demonstration at the conference; before the opening, South African groups organized a 5,000-strong protest march from Durban City Hall to the conference center. In his plenary presentation, Fauci said the first hints that highly active antiretroviral therapy (HAART) was not wiping out HIV came in 1997, when several research groups found they could find the virus, even in patients who had been on the therapy for up to three years and who had no detectable level of HIV in their blood.

''That was the first sign we were not eradicating HIV,'' Fauci said. The next step was to try to attack the reservoirs in which HIV hides, he said, but even when that seemed successful, the virus rebounded when HAART was stopped. The rebound occurred even in two patients who seemed to have no detectable virus in any part of their body, he said.

''The virus has the uncanny ability to reestablish a reservoir,'' Fauci said. ''Even our most rigorous attempts to reduce or eliminate the reservoir had been unsuccessful.'' But, he said, there were experimental hints that HIV took some time to rebound after HAART was stopped, which suggested that deliberately interrupting therapy for defined periods might not cause any harm.

On the positive side, he said, it would also be cheaper, have fewer side effects and be easier for patients to follow.

In early data from NIAID tests on human subjects, Fauci said, interrupting therapy either one week on, one week off or two months on, one off appears to control the virus as well as constant treatment, while reducing the cost.

He said it's still too early to know whether there will be fewer side effects, but the test subjects are excited about avoiding the ''extraordinary burden'' of the pill-intensive HAART, in which patients must take as many as 40 pills a day.

But he added that physicians shouldn't move too quickly: ''Don't try this until the trial is complete,'' Fauci said.

One fear in interrupting therapy is that the virus will be able to revive and perhaps evolve strains resistant to the drugs. But Fauci said that fear only applies to ''suboptimal therapy,'' in which patients don't follow treatment plans, and is unlikely to arise in his interrupted therapy.

Fauci's conclusion that no cure is likely was echoed by David Ho of the Aaron Diamond AIDS Research Institute in New York, one of the leaders only a few years ago in proclaiming that then-new drugs might wipe out HIV, the virus that causes AIDS.

At the Vancouver AIDS conference in 1996, Ho was perceived to be claiming that HAART would cure HIV infection, although he said this week he had been more cautious and his position was misinterpreted.

The hope that HAART could wipe out HIV, Ho said, was based on two ideas, both later proved to be wrong: That the drugs would completely stop the virus from reproducing and that there were no ''compartments'' in the body where the virus could hide.

The admission that a cure is still not in sight came as researchers for the Centers for Disease Control said HAART is not as effective in suppressing the reproduction of HIV as scientists had earlier hoped.

Researcher Scott Holmberg said HAART is effective for more than 12 months in only about one-third of patients. Others, Holmberg said, must regularly change their drug regimes in order to maintain low blood levels of HIV, which means that drug options ''are increasingly being exhausted by the people who need them.'' Holmberg, analyzing medical data from more than 1,600 AIDS patients across the U.S., found that HAART use has climbed from 4 percent at the end of 1995 to 87 percent in late 1999. At the same time, AIDS deaths dropped by more than 90 percent.

But HAART failed to keep virus levels low for more than a year in 64 percent of patients, Holmberg said. Those who changed their drug regime because the virus become resistant or because side-effects were too extreme were less likely to keep HIV levels low.