/ 1 January 2002

New class of drug suppresses HIV

The first in a brand-new class of drug has yielded excellent results in suppressing HIV among patients with a chronic history of fighting the Aids virus, doctors said on Monday.

Speaking on the sidelines of the 14th International Aids Conference here, they said the drug was the first big innovation, although still not a cure, in the battle to treat HIV since the emergence of antiretrovirals in the mid-1990s.

The molecule, a so-called fusion inhibitor named enfuvirtide, enabled patients to recover from an immune system that had been almost wrecked by sky-high levels of the human deficiency virus (HIV) in their blood and a rock-bottom level of CD4 immune cells.

The two companies behind enfuvirtide, the Swiss pharmaceutical giant Roche and Trimeris Inc. of the United States, announced they would now file a request this year to market the drug, codenamed T-20, in the United States and Europe after its successfully final trials on 1 000 volunteers in 112 locations worldwide.

Jacob Lalezari, director of a US company Quest Clinical Research who assessed enfuvirtide among patients in San Francisco, said he had witnessed ”a spectacular, I would hate to say it, miraculous recovery” among those who had taken T-20.

”Do we see a clinical benefit from this degree of viral suppression? Yes we do,” he told a press conference.

”These efficacy findings are very gratifying indeed.” Although HIV was first identified as the cause of Aids more than two decades ago, there is still no cure or vaccine for it.

The best available treatments are protease inhibitors, which target enzymes that help the human immunodeficiency virus (HIV) to reproduce after it enters the CD4 immune cell.

This antiretroviral ”cocktail” has enabled many people — overwhelmingly in rich countries that can afford them — to lead a normal life.

For them, it has reduced HIV levels, called the viral load, to below detectable levels, although the virus springs back if the drug is not taken.

But in many others, the protease inhibitors have toxic or unwelcome side-effects; they have to be taken in complex, daily multiple doses; and there are worrying signs that the notoriously mutating Aids virus is becoming resistant to them.

Fusion inhibitors aim to stop HIV from entering the CD4 cell in the first place.

The goal is to block the way the virus docks onto the cell surface with its gp120 protein, which is followed by a harpoon-like manoeuvre by a second protein, gp41, that penetrates the cell membrane.

Once the viral and host cell membranes have fused, the virus is able to spew its genetic material into the host cell, thereby infecting it and opening the way to its own reproduction.

T-20 is technically a synthetic peptide formulated to attach itself onto a region within gp41, preventing it from carrying out its harpoon act.

Two batches of 500 patients took part in T-20’s Phase III trials. After 24 weeks, between 28 and 37% of those who took T-20 with selected antiretrovirals had achieved a reduction in viral load to below detectable levels, whereas the figure among those who took the protease cocktail was only 14 and 16%.

In addition, the number of CD4 cells after 24 weeks was double among the T-20 group compared with the patients who did not receive the new drug.

Tolerance to the drug was considered excellent. The drug’s likely role is that it will be a salvage therapy for chronically infected people who cannot use classic antiretrovirals, Trimeris and Roche officials said.

Its downside is that, unlike protease inhibitors which are taken orally as tablets, it has to be injected under the skin, using a simple insulin-like injector. Three percent of volunteers abandoned T-20 because of problems encountered with this.

Keeping the stored drug continuously refrigerated could be a major problem in sub-Saharan Africa, home to 70% of the 40-million people with HIV today.

Roche’s head for fusion inhibitors, David Reddy, said the more important priority would be to get protease inhibitors distributed in Africa, where only a few tens of thousands of people have them at the moment.

Trimeris’ chief executive officer Dani Bolognesi, said the two firms had not yet decided how much T-20 would cost. A second drug, T-1249, is currently undergoing Phase I and II tests. – Sapa-AFP