Novel Approaches to Eliminating HIV Latency
Technical Report,15 Sep 2018,14 Sep 2019
Florida International University Miami United States
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With the advent of combination antiretroviral therapy, HIV has become chronic but manageable illness. However, people living with HIV continue to suffer comorbidities due to underlying viral replication even in presence of antiretrovirals. Cessation of antiretroviral therapy or missed doses leads to a restoration of viral p24 counts in the serum suggesting a rebound of the virus from anatomical reservoirs. Moreover, low level viral replication and gene expression ensures expression and secretion of viral proteins like Tat which can by themselves contribute to HIV associated comorbidities. A number of sites have been suggested as potential anatomical reservoirs, including resting CD4 cells, monocytes, macrophages, astrocytes, etc. Eradicating HIV reservoirs can lead to a cure for HIV while also decreasing the overall viral burden and decreasing the incidence and severity of HIV associated comorbidities. Given that the principal mechanism by which latency is established is by sequestration of the Positive Transcription Elongation Factor-b PTEF-b, activating PTEF bin HIV reservoirs will lead to viral replication. Replication in presence of antiretrovirals will eliminate the infected cell and prevent denovo infection. We will couple an siRNA with an aptamer targeting an HIBV protein called gag. This will ensure that only infected cells will receive the siRNA to reactivate PTEF-b which in turn will reactivate the dormant virus.
- Medicine and Medical Research