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Despite efficient combination of the antiretroviral therapy cART , which significantly decreased mortality and morbidity of HIV-1 infection, a definitive HIV cure has not been achieved. Hidden HIV-1 in cellular and anatomic reservoirs is the major hurdle toward a functional cure.
These cells are believed to be involved in the emergence of drugs resistance and reseeding peripheral tissues. Clearing these infected cells from the brain is therefore crucial to achieve a cure. However, many characteristics of microglial cells and the CNS hinder the eradication of these brain reservoirs. Better understandings of the specific molecular mechanisms of HIV-1 latency in microglial cells should help to design new molecules and new strategies preventing HAND and achieving HIV cure.
Moreover, new strategies are needed to circumvent the limitations associated to anatomical sanctuaries with barriers such as the blood brain barrier BBB that reduce the access of drugs. Since the introduction of the combination antiretroviral therapy cART in the fatal evolution of the HIV-1 infection has stopped and became a chronic disease. However, despite continual efforts definitive cure has not been achieved.
This is mainly due to the lack of efficient vaccination and to the existence of viral reservoirs. Indeed, as soon as the treatment is interrupted, a viral rebound is observed within a couple of weeks and viremia is comparable to the one encountered before the introduction of cART Davey et al. Moreover, with ultrasensitive methods, we can still notice a residual viremia in patients under cART Dornadula et al. In addition, some of these reservoirs are found in sanctuaries such as the genital tract, the adipose tissue, the bone marrow and the brain.
