HIV persistence and viral reservoirs

Antiretroviral therapy (ART) does not eradicate HIV: A small pool of latently infected cells, usually referred as the “reservoir”, provides a long-lived source of rebound viremia. The overarching goal of our research is to characterize and interfere with the mechanisms that contribute to the maintenance of the HIV reservoir during ART.

 

Our research goals are:

(i) To determine how the timing and duration of ART affect the distribution of the reservoir in tissues and cell subsets

(ii) To characterize the molecular mechanisms responsible for HIV persistence in the sub-populations of cells in which it persists

(iii) To design innovative therapeutic strategies to reduce the size of the latent reservoir with the ultimate goal of developing a functional cure for HIV infection. 

Why do we need a cure?

ART does not cure HIV infection. Treatment for HIV is is a lifetime treatment. There are at least 4 reasons why we need to do better than current treatment. 

i) People living with HIV are sill stigmatized and criminalized in many regions

ii) Antiretrovirals may have some toxicity. The very long term effects of ART are largely unknown.

iii) Not everybody has access to the treatment. Access to ART for all is a formidable challenge.

iv) HIV still generates enormous costs in terms of human suffering, job loss and its related economic impact, and financial burden on health care systems

Why do we not have a cure?

Although antiretrovirals are very efficient at controlling HIV replication and disease progression, they do not eradicate the virus. HIV persists in reservoirs in all people taking ART. Reservoirs are cells and tissues in which the virus persists at low levels. These reservoirs are insensitive to current HIV drugs and represent the main barrier to an HIV cure.

HIV can persists though a variety of mechanims:

i) It can still replicate at low levels in some tissues in which HIV drugs do not diffuse optimally

ii) It hides in "resting cells" that have the ability to persist for decades

iii) It also hides in cells that proliferate and that duplicate the HIV genome during each division

Eradicating HIV will require to target all mechanisms of persistence and all cells and tissues in which HIV persists.

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