The purpose of the CLEAR study was to investigate whether a cancer medicament called Panobinostat could help the immune system detect and kill the cells hiding HIV in infected patients.

Today HIV patients are given a treatment that is so efficient, that the virus cannot be detected in the blood. Even so, HIV still ‘hides’ in the immune cells, and the virus will be reactivated as soon as the treatment is interrupted.

The CLEAR study is based on the “Kick and Kill” strategy: First HIV is reactivated and made visible in the latent infected cells; second the immune system eradicates the virus.

Panobinostat is a histone deacetylase inhibitor (HDAC inhibitor) that has proven to be very efficient in reactivating HIV. The HIV hiding in the latent infected cells is known to be the primary challenge in curing HIV. Therefore it was relevant to investigate, if Panobinostat could be used to lower the total viral load in well-treated HIV patients.

Research questions:

In the CLEAR study we wanted to answer the following questions:

• Is it possible to reactive the virus in latent infected cells by using Panobinostat?
• If so, is it possible to detect that the total viral load or the number of latent infected cells is being reduced?

15 chosen HIV patients participated in the CLEAR study, and the first blood test was done on the 1’st of October 2012. Through a period of 8 weeks the patients received treatment with Panobinostat 3 times a week every second week. During this period blood tests were made regularly to show that the medicament activated the virus. After the treatment we investigated whether the number of latent infected cells had been reduced. The results created a stir and have since been presented in HIV conferences in Kuala Lumpur, Miami and Boston in 2013 and 2014.

Results:

The Panobinostat treatment lead to a considerable reactivation of the latent virus, and it was possible to detect it in the blood. This has not been possible in any other study with the same strategy, and the results are considered to be crucial in making the infected cells visible for the immune system.

The treatment did not lead to a reduction in the total viral load (the HIV reservoir) among the 15 participants in the study. The most evident explanation to this is, that the immune system doesn’t make a response that is sufficient enough to eradicate the virus.

Conclusion:

The experiment showed that Panobinostat is able to activate latent virus in resting immune cells, and following analysis have suggested some characteristic immunological features among the patients, that can determine whether the activation of the virus will lead to a reduction in the total viral load. These results are crucial for the structuring of future studies, where Panobinostat or mutual medicaments will be combined with treatments that aim to strengthen the immune response against HIV.