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AIDS – Researchers from the Pasteur Institute destroy HIV reservoirs

A team from the Pasteur Institute in Paris has found a way to eliminate HIV reservoirs, paving the way for potential new treatments, but there is still a long way to go before the results, which were obtained using cell cultures, are used in humans.

Current HIV treatments need to be taken for life because antiretroviral drugs are not able to eliminate the viral reservoirs inside immune cells.   “Antiretroviral treatment will block the virus and act to prevent it from multiplying, but it cannot eliminate infected cells.  Here, our job involved characterizing infected cells and then eliminating them from an organism infected by HIV” explained leading researcher, Asier Saez-Cirion.

The Pasteur Institute team succeeded in identifying the characteristics of CD4 T lymphocytes, the immune cells targeted by HIV.  Their study shows that the virus will first infect cells with a high rate of metabolic activity.  This activity, and in particular a cell’s glucose consumption, plays a key role in infection: the virus diverts the energy and substances produced by the cell in order to replicate.  This requirement could be harnessed to attack reservoir cells.  The results are published in Cell Metabolism.

HIV infection blocked in cell cultures

The Pasteur researchers managed to block infection ex vivo (in cell cultures) thanks to metabolic inhibitors already used in oncology/cancerology.  “In our study we observed that those cells infected by HIV had (bio-)energetic characteristics similar to tumor cells, and we could therefore use the same tools” explained Dr Saez-Cirion.  The next step for the team at the Pasteur Institute will consist in “identifying the molecules which provide an optimal effect, after which pre-clinical trials on models will be undertaken, based on experience from current clinical trials on the treatment of certain types of cancer, in order to select molecules that are efficacious and well-tolerated by patients,” the researcher added.

This work is a step towards patient remission (no further detectable infected cells) thanks to the elimination of HIV reservoirs.  However, “it will be a few years until this approach can be properly tested in a phase 3 clinical trial which would give us an evaluation of its efficacy” Dr Saez-Cirion specified.

1. Voici le document autour du glossaire.
2. Traduction de l’article sur le vaccin :

HIV: Is an AIDS vaccine possible?

Everybody dreams/is dreaming about a vaccine for AIDS.  And now trials published by researchers from Harvard bring new hope. Their experimental vaccine was able to protect monkeys and cause an immune reaction in humans.

According to the World Health Organization about 37 million people worldwide are currently living with HIV or AIDS.  No less than 1.8 million new cases are reported each year.  Since the early eighties the disease is thought to have (/has reportedly) killed almost 35 million people.  And despite increasingly effective treatments a vaccine still doesn’t exist for this scourge.

Worse still, in 35 years of this epidemic only one experimental vaccine has shown any efficacy.   During the RV144 trial carried out in Thailand from 2003 on(wards) the immune response was prepared by the administration of a recombinant vector CanaryPox then boosted by (the) injection of the envelope protein gp120.  As a result, infection rate was seen to decline by 31%, which was interesting, but judged to be insufficient.

But today, researchers from Harvard have reported encouraging new developments.  The experimental vaccine they developed triggered an immune reaction in humans and protected monkeys from the infection.  “These results are crucial.  They must however be considered with the utmost prudence.  An immune response doesn’t necessarily mean that this vaccine is able to protect us from HIV (infection)” warned Professor Dan Barouch.

Large-scale trials already underway

What has caused great enthusiasm is the fact that the vaccine is a mosaic vaccine, which combines different HIV subtypes and is therefore likely to trigger responses against a large number of strains.  Indeed, the results show it is 67% effective in monkeys.  Here again, the reaction was primed by (an) intramuscular injection of Ad26.Mos.HIV.  The response was then stimulated later on by the administration of two additional vaccines including a combination of Ad26.Mos.HIV and gp140.

In humans: The study reports on the results of a test carried out on 393 healthy adults who were all seronegative, aged 18 to 50, and from East Africa, South Africa, Thailand and The United States.  Between February and October 2015, they received four injections of one of the combined vaccines or a placebo.  According to Professor Barouch, the immune response was “robust’.  Another good sign was that the vaccine was shown to be harmless.

A large-scale test still needs to be carried out to gauge the true efficacy of the vaccine.  The test is already in the starting blocks and will involve 2600 women judged to be at risk in Southern Africa.  The results are not expected before 2021 or 2022.