Immune activation and Viral load suppression in HIV patients
HIV is a chronic debilitating disease, it can't be cured permanently by antiretroviral therapy (ART). However regular intake of ART suppresses viral replication and resultantly lymphocytes start increases. As you know HIV virus attacks on CD4 T lymphocytes. This process will ultimately improve the health condition of patients living with HIV.
Cure is a myth in cases of HIV . Yes the disease can be managed to keep pt healthy with good qol
Dear Shimelis Teshome Ayalneh , thanks for posting this important topic. In humans, immune activation unfortunately never lead to HIV eradication, once HIV infection has been established. Even if immune activation is strong and in the same time HAART is initiated in a HIV positive person, this will in optimal case lead to undetectable HIV state in blood with commercially available tests, but HIV will remain in this persons in dormant state. HIV can unfortunately directly infect human CD4+T cells that revert to a G0 dormant memory state, thus enabling the virus to enter latency. It has been suggested that latency may be established by direct infection of resting memory CD4+T cells (Trm cells) . Selective reverse transcriptional products tyrosine aminotransferase (Tat) and negative factor (Nef) exist in Trm cells and can induce cell activation so that the virus genome can be integrated into the cell genome. In such cells HIV can persist even for decades, and HAART, which is designed to inhibit only active replication steps, cant reach a HIV-provirus. Also , the immune system cant recognize T-cells with dormant HIV and destroy them-for this the infected cells needs sufficient surface alerts which would provide the immune system a signal to attack this cells. It has also been found in experiments that although Trm cells are resistant to HIV compared with activated, hIV-permissive CD4+T cells, only a mild stimulation of chemokine CC ligand 19 and chemokine CC ligand 21 and cytokines interleukin (IL)-4 and interleukin (IL)-7 can promote the direct infection of resting CD4+T cells with HIV without inducing significant T cell activation. So, to eventually come to a realistic HIV cure one day, we will need an efficient antiretroviral replicating therapy (similar as HAART) AND an efficient anti HIV-proviral therapeutic tool-something like CRISPR/Cas9 System, only with excellent selectivity and without any off target actions. Of note, also HIV-attachement blocking genetical engineering startegies are of huge interest (gp120, CCR5, CXC4 targeting pharmacons). To realize all this, we still have a Hercules work to do. Good luck & thanks for this importent discussion !
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