Currently, many people living with a HIV+ health status can have their viral load reduced to undetectable using a life-long antiretroviral therapy (ART). ART has proven to be effective but it has to be taken indefinitely to prevent rebound of viremia and re-emergence of symptomatic disease. There are several avenues that HIV attains latency, but one of these latency mechanisms includes the recruitment of histone deacetylases (HDACs) to the region on the HIV long terminal repeat (LTR) promoter. This mediates the formation of a repressive chromatin environment that inhibits LTR expression and HIV viral production. Therefore, when ART is taken continuously it helps prevent latent disease from the persistence of long-lived viral reservoirs in host cells. However, this potential for recurrent disease remains the unfortunate limitation to HIV eradication using ART so the need for continual research and developing innovative therapies to control HIV-1 infection beyond the limitations currently available with ART.
Consequently, previous studies have demonstrated that HDAC inhibition serves as an antagonist for the repression of HIV transcription so it has been investigated as a tool to reverse HIV latency in humans. Additionally, exposure to a known HDAC inhibitor vorinostat (VOR) has been shown to induce HIV antigen expression at a sufficient enough level to allow for host viral clearance in vitro. The above mentioned case study presents the results of combining a validated latency reversing agent (VOR) along with an immunotherapeutic (AGS-004) shown to generate a HIV-specific immune response. AGS-004 is a dendritic cell (DC)-based immunotherapy. The agent/vaccine consists of matured autologous DCs co-electroporated with in vitro transcribed ribonucleic acid (RNA) encoding autologous HIV antigens. Having these antigens helps to achieve DC functionality. According to the study, “this vaccine was reported to induce HIV-specific effector/memory CD8 T-cell responses in HIV-infected individuals who had initiated ART during acute or chronic infection.” The results were not completely what they hoped for since there were “no measurable impact on the replication competent reservoir as measured by QVOA assay.” However, there was some promise shown that DC-based HIV vaccines can have a slight improvement in HIV specific T cell responses. I think having DC immunologic therapy is promising and for all the millions of people living with this chronic disease.
Finally, T cell and DC-based immunotherapies have also been tested for the treatment of cancer patients but it has only shown limited success. One of the problems observed was the ineffective activation of specific T-cells by the injected dendritic cells in vitro. However, it is showing promise in vitro since memory T-cells were generated and induced an immune response that could circumvent the ineffective T-cell activation. Therefore, this approach demonstrated that it could greatly enhance the efficiency of cancer immunotherapy if it could be made to be reproducible in vivo. This is especially exciting since cancer and HIV affect so many of us in one way or another and it is claiming the lives of many of our loved ones. Maybe during our generation we’ll see the emergence of a refined methodology where DC-based immunotherapy could induce the appropriate T cell response that would provide the needed break-through for these deadly diseases.
Microbiology and You 