/ 11 July 2003

Aids blunts treatments and laughs at vaccines

Scientists from around the world gather in Paris this Sunday for an update on the war against Aids, gloomily aware that good news will be rare and that, after more than two decades, they still lack basic knowledge about their foe.

The four-day forum comes on the heels of President George Bush’s tour of Aids-stricken African countries, where his pledges show that the political will and funding to fight the global scourge are at last being mustered.

Yet that upbeat sense contrasts with the dour mood in the lab, where progress against the human immunodeficiency virus (HIV) — a crafty enemy that blunts treatments and laughs at vaccines — is at best millimetric.

In its documented 22-year history, HIV has infected more than 60-million people, over a third of whom have died from the disease it causes, acquired immune deficiency syndrome (Aids). Each day, 14 000 people worldwide join the army of infected.

”Unfortunately, the catastrophic potential of the Aids pandemic has not yet been fully realised,” said Anthony Fauci of the US National Institutes of Health (NIH), in a special issue of Nature Medicine to coincide with the conference.

”HIV and Aids continue to exact an enormous toll throughout the world, notably in sub-Saharan Africa, and their incidence is accelerating in some countries and regions, including China, India and parts of eastern Europe and central Asia.”

Some 5 000 people, a third of them involved in fundamental research, are registered for the conference, an event that is held every two years and alternates with the International Aids Conference, staged in Barcelona a year ago.

Highlights include a speech by former South African president Nelson Mandela; the latest research on HIV drugs and fresh worries that the virus is becoming immune to them; an update on the search for a HIV-killing cream that can be used like a spermicide; and new studies on mother-to-child prevention and vaccine trials.

Researchers are eagerly awaiting the results from trials of a new class of so-called fusion inhibitors — drugs which seek to prevent the Aids virus from attaching itself to an immune cell, the first step towards penetration and infection.

Early studies suggest that fusion inhibitors are especially powerful for individuals whose immune systems have been almost wrecked. They are the third and most promising generation of HIV drugs — an evolution that began in 1987 with the introduction of AZT, initially licenced as a cancer drug and was followed in 1995 by the advent of highly active anti-retroviral therapy (HAART), the triple cocktail of anti-HIV drugs.

None of these treatments is a cure, and they often have toxic side-effects. And their cost has inflamed bitter rows about pricing and access for patients in the Third World, which is bearing the brunt of the pandemic.

HAART slashes back viral levels to below detectable levels. But the virus then holes up in ”reservoirs” in the body, believed to be the lymph glands, and then bounces back as soon as the patient stops taking the drugs. New research published last week suggests it does this trick by sending out a complex cascade of signalling molecules that opens up a ”resting” T cell to a passing virus, thus reviving the cycle of infection and replication.

The blank spots in our knowledge, said Fauci, are agonisingly evident when it comes to vaccines.

Aidsvax, the only candidate to see through the three phases of trials — it tried to prime antibodies to recognising the gp120 protein on the surface of the virus — has been a sad failure. That has placed the emphasis on another path: encouraging defence by immune cells.

”In the absence of a vaccine … the future is prevention and treatment,” said conference co-chair Jean-Francois Delfraissy of the Bicetre hospital of Paris. – Sapa-AFP