2023-05-21 11:30:40
AFP
HIV drugs: from AZT to triple therapy
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…- L’AZTWhen HIV appeared in the early 1980s, patients were condemned to death in the short or medium term, and no drug 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, who owns the molecule, will test it in a clinical trial: the latter will stop at phase 2, without going until phase 3 – the last stage before marketing -, as the results are good. March 20, 1987, the first antiretroviral treatment AZT is 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, the 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 completely 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. in 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 main types of antiretroviral drugs, which will act at different stages replication of the virus, including the very latest, integrase inhibitors, which mark new progress. More and more, work is being carried out to make the treatment much less burdensome, with less regular doses. PrEPOn 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 enabled people at risk to protect themselves by taking a tablet as a preventive measure.- Transplants There have been three confirmed total cures of patients with HIV thanks to transplants. The patients, suffering from blood cancers, benefited from a stem cell transplant, which deeply 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? This 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 also become invisible, hiding in reservoirs, before reappearing years later. So far, all vaccine attempts have ended in failure. 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. “This is the main hope”, judges Victor Appay. “A lot of research is being done to generate broad-spectrum antibodies, which will target the greatest number of strains of HIV”.lem/cel/as
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