MARSEILLE — Thirty years since the beginning of the AIDS epidemic, therapeutic leads against the virus are finally starting to appear clearly, making the notion of a cure realistic.

"Science has never been so close to breaking the mutation mechanism that protects HIV from the body's natural defense system," explains Michel-Paul Correa, director of the International Institute for the Development and Support of Innovative Scientific Research.

His scientific committee, headed by the man who co-discovered the virus, French virologist Claude Chermann, has pinned its hopes on a series of experiments that target the enzymes necessary for the virus to multiply or the receptors that enable it to enter the cells.

The most advanced research projects are those being carried out by French startup Biosantech, which is developing a vaccine that "provokes an encouraging immune response," says Dr. Jean Bora de Mareuil, head of the company's research and development. The molecule this biotechnology company developed targets the Tat protein, which enables the virus to multiply.

The scientific community is well acquainted with this key protein. In the 1990s, one of its variants was identified in a young Gabonese woman named Oyi, who carried the virus but was in good health, as were her three children, all born HIV-negative. "We formulated the hypothesis that a synthetic active ingredient derived from Tat Oyi (the variant found in the Gabonese patient) acted like an "anti-Tat" protein, preventing the virus from multiplying," de Mareuil explains. "By neutralizing it, we allow the body to restore its cellular immunity so it can eliminate the contaminated cells by itself."

Tested on HIV-infected monkeys, Tat Oyi has proved to be as efficient as it was in the study on Gabonese patients. Harvard University researchers confirmed the results, saying that it was indeed the Tat Oyi protein that, by producing the adequate antibodies to fight against the Tat protein, enabled monkeys to resist the virus. In France, Marseille-based Erwann Loret, the researcher who started the experiments, and his team at the National Centre for Scientific Research (CNRS), filed a patent for which Biosantech has the exclusive license.

From monkeys to people

Human trials began in April 2013, and the tests on 48 HIV-positive patients have proved the absence of toxicity in the vaccine. Phase two should be complete by the end of the year. It's expected to determine what dosage is the most efficient to produce anti-Tat antibodies.

Divided into three groups, each patient received three injections of different concentrations or a placebo before their triple combination therapy was halted for two months. "Several patients continued to show a very low level of viral reproduction after the interruption of their therapy," de Mareuil says.

There will be a new trial in 2015 with 80 additional patients to test the absence of side effects and confirm the treatment's efficiency. The goal is to have at least 30% of patients with an undetectable virus after their treatment is suspended. If that's successful, a final study will test the vaccine on a large scale according to UNAID norms by comparing it to placebos and reference treatments.

Anti-Tat is not the first vaccine to be assessed. Over the last three decades, more than 600 clinical tests have been conducted. None went beyond phase one. Before the summer, Biosantech managed to raise 800,000 euros ($1 million) from 107 investors, making it the most important crowdfunding campaign to date in France.

But the vaccine isn't the only promising lead. In early November, virologist Didier Raoult from the Méditerranée Infection foundation, and the team of professor Yves Lévy, the new president of the French National Institute of Health and Medical Research, made a significant discovery. They demonstrated that a previously unknown anti-viral enzyme called Apobec was not activated by the AIDS virus. That suggests that "the reactivation of this enzyme could open up new prospects to cure the disease," Raoult says.

This hypothesis originated from the observation of how the virus evolves in koala bears. The infected animals have spontaneously recovered by integrating the virus in their genes until they were able to neutralize it and transfer their immunity to their offspring. The same thing is happening among humans. "About 8% of the human genome contains deactivated retroviruses," Raoult says.

Concerning AIDS, the so-called "endogenization" process — basically, spontaneous cure — has been observed in at least two HIV-positive patients. Their genome sequence showed that the virus was unactivated, probably because of the action of the Apobec enzyme on the DNA of the virus. One of these patients, aged 57, is now considered cured, 30 years after being diagnosed with HIV.