As researchers who participated to the "International Workshop on HIV Persistence, Reservoirs & Eradication Strategies" last week in St Martin are heading back to their labs and clinics, they bring with them new data and ideas to work faster towards an HIV cure.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 with more details this study is posted here: http://www.youtube.com/watch?v=_fhb95p__9g&feature=youtube_gdata_player
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.
About the workshop: the "5th International Workshop on HIV Persistence, Reservoirs & Eradication Strategies" was held at the Westin St
Maarten Hotel, Philipsburg, December 6-9, 2011. It is a closed meeting where participants are selected for their commitment in HIV
About the workshop: the "5th International Workshop on HIV Persistence, Reservoirs & Eradication Strategies" was held
at the Westin St Maarten Hotel, Philipsburg, December 6-9, 2011. It is a closed meeting where participants are selected for their
commitment in HIV persistence research. Website: http://www.informedhorizons.com/persistence2011
Press contact: Alain Lafeuillade, MD, General Hospital, Toulon, France; lafeuillade(at)orange(dot)fr