New leaps towards HIV remission and cure

More than 210 international scientists met from December 6 to December 9 in Philipsburg for the "5th International Workshop on HIV Persistence, Reservoirs and Eradication Strategies". The American National Institute of Health (NIH) and the French Agency for AIDS Research (ANRS) were supporting this workshop.

This meeting is devoted in part to human trials testing new strategies towards a HIV cure, either functional or sterilizing. A functional cure is a situation where persistent HIV reservoirs are controlled by the body without needing permanent antiretroviral therapy. A sterilizing cure is a situation where HIV has truly been eradicated from the body.

Current combined antiretroviral therapy (cART) is able to keep HIV replication in blood at bay but the infection rekindles each time these drugs are stopped due to the existence of HIV reservoirs. The reservoirs contain latently infected cells, which are not influenced by all the currently available drug classes. Life-long cART is, however, not the definite answer because of compliance, resistance, toxicity and cost issues. New strategies are therefore needed to attack the HIV reservoirs in cART-controlled patients.

In a collaborative study, Professor Mario Stevenson (Miami, USA), Timothy Schacker (Minneapolis, USA) and Courtney Fletcher (Omaha, USA) addressed the issue whether cART is potent enough beyond the blood compartment to completely stop HIV propagation. They analyzed intracellular drug levels in patients with undetectable plasma viremia on cART in PBMC and cells taken from lymph nodes, terminal ileum and sigmoid colon at different time points after therapy was initiated.

Surprisingly, they found important differences between drugs, and patients, with suboptimal drug concentrations in lymphoid tissues, which were associated with ongoing viral propagation at this level. These data show that we have first to improve our cART potency in tissues in order to stop the replenishment of the HIV reservoir.

An interview of Professor Stevenson describing more details of the study.

Another question is whether some drugs can purge the latent HIV reservoir.

Professor David Margolis (Chapel Hill, USA) presented the preliminary results of an ongoing trial using vorinostat to reactivate this latent reservoir. Vorinostat is an anti-cancer agent that has been shown capable to reactivate HIV from cells in vitro.

This trial is at its very beginning and tests in the first place a unique administration of vorinostat. The drug tolerance was good and markers of HIV replication were increased in resting cells, which are the last hiding place for HIV.

These results are very important because there was some concern that vorinostat could be toxic or not potent enough to awaken latent HIV. A trial conducted in Australia by Sharon Lewin involves an administration period of 2 weeks of vorinostat. Although Professor Lewin did not have efficacy data to show at the workshop, she said in the discussion that the overall tolerance was also good in her study.

The next edition of the "International Workshop on HIV Persistence, Reservoirs & Eradication Strategies" will be held in Miami from December 3 to 6, 2013. Researchers therefore have 2 years to make theses advances towards an HIV cure a more tangible fact for patients.