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HIV Reservoirs: Four main questions for 2011 Toulon, France, January 5, 2011 -- Despite effective antiretroviral combinations (HAART) capable of totally blocking the Human Immunodeficiency Virus (HIV) replication, this retrovirus persists life-long in patients due to the existence of hidden reservoirs. Major advances have been made since the first description of these HIV reservoirs in 1997 but a handful of fundamental questions remains to be elucidated before trying to find a cure. Question 1: What is ‘the’ HIV Reservoir and Where is it Located? The majority of the long-term HIV reservoir is situated in CD4+ T lymphocytes. These cells keep the memory of the immune system and are long-lived. We also know that within these CD4+ lymphocytes, the HIV reservoir is located in the central memory and transitional memory sub-populations. The HIV reservoir is 10 fold higher in the gut than in the blood and, in the brain, infected astrocytes could be the principal cells responsible for HIV persistence. On the contrary, data on other HIV reservoir cells are scarce (Stem cells? Macrophages? Other sorts of cells?) as well as on different body compartments than the gut and the brain. Question 2: What other factors than the virus play a role in the HIV Reservoir? There are at least some recognized genetic factors and immune factors. For example, ‘elite controllers’ (patients controlling HIV replication themselves without the need of HAART) have a better CD8 antiviral response, leading to a kind of protection of the central memory CD4+ T cells, and this is associated with the presence of HLA B27 and B57 markers. However, the exact nature of the immune response that could be able to control a very tiny HIV reservoir remains uncertain. Question 3: What current HAART can do on the HIV reservoir? The HIV reservoir is established very early, at the time of acute HIV infection. Treating HIV with HAART at the chronic stage of the disease is unable to decrease the HIV reservoir. However, it is highly likely that initiating HAART very early, at acute infection, limits the HIV reservoir size and the damages done to the immune system. Nevertheless, the clinical benefits of this early approach still need to be proven. It is also unknown if there is a threshold below which we can drive the HIV reservoir size and this one will not rekindle when HAART is discontinued. Finally, almost nothing is known on antiretroviral drugs activity in cells from different tissues. Question 4: Can the HIV Reservoir be targeted and how? The most advanced theory is the HIV reservoir ‘purge’, i.e. activating latently infected cells in the presence of HAART to make them die or killed by the immune system. The main candidates are Histone Deacetylase Inhibitors (HDACi) and Interleukin-7 (IL-7). There are concerns that IL-7 would not be strong enough to reactivate the HIV reservoir, or even help expand it, and that HDACi could put the brain HIV reservoir beyond control. Preliminary results of small pilot studies testing these new strategies are urgently needed. About us: Since the year 2003 we are committed in HIV reservoirs research and organize every 2-year the reference scientific workshop on HIV reservoirs. The next edition in December 2011 will address all these issues and much more (

Contact: Alain Lafeuillade CHITS 1208 Av. Col. Picot, 83056 Toulon, France Ph: +33494616340 E-Mail: Web:

HIV Reservoirs: Four main questions for 2011