February 14, 2022
The Challenge of Latent HIV
One of the biggest challenges facing clinicians treating HIV is the phenomenon of latent HIV, where the virus can essentially “hide” from the antiretroviral drugs that kill viral particles circulating in the blood.
Without being able to eliminate the latent form of HIV, patients will have to be on antiretroviral HIV drugs for the rest of their lives once infected.
PD-1 in HIV Infection
HIV is an infection of immune cells, specifically T cells. Although treatment clears the virus circulating in the blood, some particles will almost always survive and stay inside T cells. When those T cells become exhausted from fighting the virus, they release a molecule called PD-1 which suppresses the immune system and renders it less effective.
PD-1 has a double effect; reducing the function of the immune system makes it harder to clear the virus, and it pushes the HIV particles into their latent form. Consequently, a lot of latent HIV particles are found inside cells expressing PD-1.
PD-1, Cancer and Pembrolizumab
Interestingly, the PD-1 pathway has also been implicated as a way that some cancer cells use to evade the immune system. PD-1 has a natural ligand, PD-L1, that is present in many types of immune cells. PD-1 binding to PD-L1 is what activates suppression of the immune system, and many cancers express PD-L1 to activate this pathway and disguise themselves from the immune system.
As such, a blockbuster therapy for cancers that express PD-L1 has been anti-PD-1 therapy, like the drug pembrolizumab (Keytruda). This drug is a monoclonal antibody that binds to PD-1, effectively taking it out of circulation and thus boosting the immune system to clear cancer cells.
Pembrolizumab Shows Promise in HIV
A recent study in Science Translational Medicine explored this link between HIV and cancer by studying the effects of pembrolizumab treatment in cancer patients with HIV. In combination with the existing antiretroviral therapy, pembrolizumab seemed to help flush out some of the latent HIV particles when it reactivated the immune system.
The Dose Makes the Poison
There are some concerns about this approach; early studies of pembrolizumab in non-cancer patients showed toxicity and unpleasant side effects and so were abandoned. However, this study opens new avenues for the most difficult aspect of HIV treatment. Researchers are testing different doses of pembrolizumab to find a dose with the most limited amount of side effects and are testing the drug’s efficacy at clearing the latent virus.
Future Directions for HIV Research
Even if pembrolizumab itself does not end up being the drug used for clearing latent HIV infection, this translational approach opens new research avenues for immunotherapies for HIV. Bioinformatics analysis will be critical in step with this research to determine if there are any biomarkers that predict HIV patient response to pembrolizumab or other immunotherapies in this exciting new line of study.
Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in the management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email [email protected] or [email protected].