Gilead and Aelix join forces to develop a promising anti-HIV combination

American pharmaceutical company Gilead Sciences - the world leader in the development of drugs for the treatment of HIV and hepatitis C - has teamed up with the Spanish Aelix Therapeutics in order to develop a fundamentally new ART-regimen, according to PMLive.

The challenge is to combine the experimental Toll-like receptor 7 (TLR7) of the vesatolimod agonist (GS-9620) developed by Gilead with the vaccine created by Aelix specialists. The peculiarity of the latter lies in the fact that its agent is based on substances generated by people who have innate immunity to HIV.

The vaccine called HTI is an immunogen that is supplied to the body in order to “re-educate” the patients' immune system so that they can control the viral load of HIV without antiretroviral therapy (ART).

Partners intend to use vesatolimod in order to activate HIV suppression in the body, including in hidden reservoirs: lymph nodes and other tissues where the virus is at rest. The goal is to enhance the immune response induced by the HTI vaccine.

Since HTI itself is designed to reorient the immune response to vulnerable points, including reservoirs, there is hope that this approach will become a “double blow” on the virus, while simultaneously affecting active and passive elements. Experts note that the use of both approaches may in the future help to completely "clean" the body of HIV.

Earlier this year, Gilead reported promising results from preclinical studies that demonstrated that vesatolimod administered to primates in combination with a neutralizing antibody in some cases, after a few months, activated the immune system and stimulated it to suppress HIV without ART.

In view of this, Gilead expects to conduct a clinical trial of vesatolimod with the best candidate neutralizing antibody.

It is expected that the Spanish study (starting in January - February 2019) will involve 90 patients who started receiving ART during early HIV infection and have an undetectable level of viral load.

As in the preclinical study, the design of the experiment will consist in the administration of a dose of vesatolimod and HTI, and then the removal of ART to check whether the combination can affect a person’s immunity in terms of HIV control.

Note that this direction of development today is extremely important.

A number of other groups are also actively working on strategies to eradicate HIV. In particular, research teams include several academic consortia led by Imperial College London, the University of Oxford, the MRC Clinical Trials Center at UCL and the University of Cambridge.

Scientists have reported that they have already conducted a study of a similar approach, known as “kick and kill,” which combines vaccines with ART and substance (vorinostat) to activate latent HIV. However, they obtained disappointing results.

“We found that parts of the kick-and-kill approach worked as expected,” said Sarah Fiedler, head of the group at Imperial College London.

"The vaccine affected the immune system, the ARV medication behaved as we expected, and the therapy suppressed the viral load [...] However, the study showed that this treatment complex does not have the potential for HIV-positive, in a form we knew about still".

Experts believe that there is no doubt that eliminating the virus in hidden reservoirs will become a “hard nut”, since earlier attempts to use high dosages and the phased introduction of ART to achieve this goal also led to failure.