“The Evolution of HIV Treatment: From AZT to PrEP and the Quest for a Vaccine”

– THAT

When HIV (human immunodeficiency virus) appeared in the early 1980s, patients were doomed to die in the short to medium term, and no medication seemed to work until the advent of AZT.

In reality, azidothymidine was initially synthesized in the 1960s as a potential cancer treatment, but was abandoned for lack of convincing results.

Against AIDS, the American laboratory Burroughs Wellcome, owner of the molecule, tested it in a clinical trial that was stopped in phase 2, one less than phase 3 – the last one before commercialization – because the results were good.

On March 20, 1987, the first AZT antiretroviral treatment was authorized in the United States, which acted on the activity of an enzyme called “reverse transcriptase”, which slows down the replication of the virus.

Unfortunately, AZT had significant side effects and was later found to be insufficient to treat HIV, since it only acted on one phase of virus replication.

– Triple therapies

An important event occurred in January 1996 with the international conference on retroviruses in Washington. Positive results were presented from various tests carried out by laboratories.

It was the arrival of a new class of drugs, antiproteases, molecules that prevent another stage of HIV replication by blocking the maturation of new proteins in the virus.

These molecules, combined with other antiretrovirals, completely changed the game.

“By targeting three stages, three molecular targets, it becomes much more difficult for the virus to escape treatment,” explains researcher Victor Appay, immunologist and research director at the French Inserm (National Institute for Health and Medicine Research).

Initially very expensive and reserved for rich countries, the therapies have become more affordable thanks to a commitment signed in 2001 at the World Trade Organization to allow developing countries to manufacture generic drugs.

There are currently five major types of antiretroviral drugs that act at different phases of viral replication.

More and more work is being done so that the treatment is much less burdensome, with less frequent doses.

– PrEP

On July 16, 2012, a first treatment called PrEP (pre-exposure prophylaxis), the antiretroviral cocktail Truvada, was licensed 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 preventive pill.

– transplants

There have been three full recoveries of HIV patients through transplantation. Patients suffering from blood cancer received stem cell transplants that completely revamped their immune systems.

The donor had a rare mutation in a gene called CCR5 that prevents HIV from entering cells. However, these transplants have only been done in rare cases, not all patients.

– Possible vaccine

It is the Holy Grail expected for four decades. The difficulty is that HIV has a powerful mutability and innumerable subvariants, allowing it to evade the little soldiers of the immune system.

It can become invisible, hide in reservoirs, and reappear years later.

So far, attempts to develop a vaccine have failed. But the work continues. A new approach is the induction of antibodies in the person through a vaccine that protects them from infection.

“That’s the main hope,” says Victor Appay. Much research is being done to generate broad-spectrum antibodies that target as many strains of HIV as possible.”