Clinical trials aimed at HIV cure or remission: new pathways and lessons learned

The main barrier to finding a cure against HIV is the latent HIV reservoir, which persists in people living with HIV (PLWH) despite antiretroviral treatment (ART). Here, we discuss recent findings from interventional studies using mono- and combination therapies aimed at enhancing immune-mediated killing of the virus with or without activating HIV from latency.

We discuss latency reversal agents (LRAs), broadly neutralizing antibodies, immunomodulatory therapies, and studies aimed at inducing apoptosis.

The landscape of clinical trials for HIV cure and remission has evolved considerably over the past 10 years. Several novel interventions such as immune checkpoint inhibitors, therapeutic vaccines, and broadly neutralizing antibodies have been tested either alone or in combination with LRAs but studies have so far not shown a meaningful impact on the frequency of latently infected cells. Immunomodulatory therapies could work differently in the setting of antigen expression, that is, during active viremia, and timing of interventions could therefore, be key to future therapeutic success. Lessons learned from clinical trials aimed at HIV cure indicate that while we are still far from reaching a complete eradication cure of HIV, clinical interventions capable of inducing enhanced control of HIV replication in the absence of ART might be a more feasible goal.