Project 466642

Antiretroviral therapies have transformed HIV from a life-threatening infection to a manageable health condition, but these drugs must be taken for life. This is because HIV establishes a latent reservoir of infected cells by integrating its DNA into the DNA of infected host cells. Antiretroviral drugs cannot eliminate cells harboring latent HIV, nor can the immune system. A theoretical strategy to cure HIV, dubbed ;kick-and-kill, aims to wake up reservoir cells by applying a strong stimulant, while boosting the immune system's ability to eliminate these infected cells. To further develop this strategy, we need to better understand what types of stimulants can safely and effectively modulate the HIV reservoir. The recent mass rollout of novel mRNA vaccines against COVID-19 gives us a unique opportunity to do so. We already know that standard vaccines (e.g. against influenza) induce generalized immune responses that can transiently stimulate HIV gene transcription. Because the novel mRNA vaccine technologies used for COVID-19 stimulate particularly strong immune responses, these may modulate the HIV reservoir more strongly. My thesis will explore the potential effects of COVID-19 mRNA vaccination on the reservoirs of 62 people with HIV on ART for whom we have collected blood samples pre-vaccination, and at various times after the first, second and booster shots, along with sociodemographic and clinical data. I will quantify HIV mRNA transcription, reservoir size, plasma cytokine levels and T-cell activation profiles before and after vaccination, and explore the magnitude of these changes with sex, age, clinical HIV parameters, and vaccine-induced antibody responses. This study will advance HIV reservoir biology towards the ultimate goal of developing an HIV cure.