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HIV drugs: from AZT to triple therapy



(AFP) – Long deadly, HIV has become a chronic disease thanks to the arrival of tritherapies in the mid-1990s. Pending a potential vaccine, which is slow to be developed, as the virus has the capacity to mutate…


When HIV appeared in the early 1980s, patients were condemned to death in the short or medium term, and no medication seemed to take effect before AZT. In reality, azidothymidine is not strictly speaking a new molecule, since it was synthesized in the 1960s as a potential treatment against cancer, then abandoned for lack of conclusive results.

Faced with AIDS, the American laboratory Burroughs Wellcome, which owns the molecule, will test it in a clinical trial: the latter will stop from phase 2, without going to phase 3 – the last stage before placing on the market – the results are so good.

On March 20, 1987, the first antiretroviral treatment AZT was authorized in the United States: it works by acting on the activity of an enzyme called “reverse transcriptase”, which has the effect of slowing down the replication of the virus.

Unfortunately, AZT – very expensive at the start – has significant side effects, and we will understand later that it is not enough against HIV, because it only targets one step of the replication of the virus.

– Triple therapies

A major event took place at the end of January 1996, with the international conference on retroviruses in Washington. The positive results of several tests carried out by laboratories are then presented. It is the arrival of a new class of drugs, antiproteases, molecules that prevent another step in the replication of HIV, by blocking the maturation of new proteins of the virus. There are also non-nucleoside reverse transcriptase inhibitors.

These molecules, combined with other antiretrovirals, will totally change the situation. “By targeting three stages, three molecular targets, this makes the probability of the virus escaping treatment much more complex”, explains researcher Victor Appay, immunologist and research director at Inserm.

At first very expensive and reserved for rich countries, multitherapies have become more affordable thanks to a compromise signed in 2001 at the WTO to allow developing countries to manufacture generic drugs.

There are now 5 major types of antiretroviral drugs, which will act at different stages of virus replication, including the very latest, integrase inhibitors, which mark new progress.

More and more, work is being carried out to make the treatment much less cumbersome, with less regular doses.

– PrEP

On July 16, 2012, a first preventive treatment called PrEP (“pre-exposure prophylaxis”), the antiretroviral cocktail Truvada, was authorized in the United States. Since then, this type of treatment has proven its effectiveness and allowed people at risk to protect themselves by taking a tablet as a preventive measure.

– Transplants

There have been three proven total cures of HIV patients through transplants. Patients with blood cancers benefited from a stem cell transplant, which profoundly renewed their immune system. Their donor indeed presented a rare mutation of a gene known as CCR5, a genetic mutation known to prevent the entry of HIV into cells. However, these transplants only concern rare cases, and cannot be extended to all patients.

– Towards a vaccine?

It is the Holy Grail that has been awaited for four decades. The difficulty lies in the fact that HIV has a powerful capacity for mutation and countless sub-variants, which allows it to evade the little soldiers of the immune system. It can further become invisible, hiding in reservoirs, before reappearing years later.

So far, all vaccine attempts have been unsuccessful. But the work continues. With a new track, the induction of “super antibodies” in the person by a vaccine aimed at protecting them from infection.

“It’s the main hope”, judge Victor Appay. “A lot of research is being done to generate broad-spectrum antibodies that will target the greatest number of strains of HIV.”

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