Clinical Interventions in HIV Cure Research.

Research over the past decade has resulted in a much-improved understanding of how and where HIV persists in patients on otherwise suppressive antiretroviral therapy (ART). It has become clear that the establishment of a latent infection in long-lived cells is the key barrier to curing HIV or allowing for sustained ART-free remission. Informed by in vitro and ex vivo studies, several therapeutic approaches aimed at depleting the pool of latently infected cells have been tested in small-scale experimental clinical trials including studies of ART intensification, genome editing, ART during acute/early infection and latency reversal. Many studies have focused on the use of latency-reversing agents (LRAs) to induce immune- or virus-mediated elimination of virus-producing cells. These trials have been instrumental in establishing safety and have shown that it is possible to impact the state HIV latency in patients on suppressive ART. However, administration of LRAs alone has thus far not demonstrated an effect on the frequency of latently infected cells or the time to virus rebound during analytical interruption of ART. More recently, there has been an enhanced focus on immune-based therapies in the onwards search for an HIV cure including therapeutic vaccines, toll-like receptor agonists, broadly neutralising antibodies, immune checkpoint inhibitors, interferon-α and interleukin therapy. In ongoing studies immunotherapy interventions are also tested in combination with latency reversal. In this chapter, the overall results of these clinical interventions ultimately aimed at a cure for HIV are presented and discussed.