The Road to an HIV Cure: Approaches and Strategies in Current Clinical Trials

OBJECTIVES: While long-acting antiretroviral therapy is a treatment strategy that allows individuals with HIV to live healthy lives without viral transmission, finding a cure for HIV has remained challenging. Current therapeutic approaches to curing HIV include stem cell transplant, gene editing, therapeutic vaccines, broadly neutralizing antibodies, and immune-based therapies. The objective of this study was to perform a landscape review of current clinicals trials to gain insight into the progress in the search for a cure for HIV.

METHODS: The study used clinical trial data obtained from the HIV advocacy organization The Treatment Action Group's (TAG) (https://www.treatmentactiongroup.org/) Listing of Research Toward an HIV Cure. Current HIV treatment strategies were assessed, categorized, and summarized to identify trends in the ongoing treatment landscape.

RESULTS: The TAG HIV cure listing showed that as of 6/15/2023 there are 295 Phase I-IV ongoing HIV trials, 73 (25%) are current and 222 (75%) are recently completed. The majority of the studies are in early phases: Phase I (44%), Phase I/II or II (42%), Phase II/III or III (5%), Phase IV (6%), and not specified (4%). This trend was observed in both current and completed trials. Regarding strategy, the results demonstrated the most common approaches are therapeutic vaccines (20%), treatment combinations (14%), antibodies (13%), intensification/early ART (9%), gene therapies (9%), latency reversal agents (5%), and immune checkpoint inhibitors (4%). For most targeted therapies, the trials were in the early phase except for intensification/early ART where Phase III & IV trials were observed.

CONCLUSIONS: The results epitomize the HIV cure landscape evolving over the next 5-10 years. Ultimately, the cure for HIV may involve any of these strategies and either alone or in combination. Understanding the current state of this research, the treatment populations, and outcomes is key to understanding whether the current HIV cure pipeline is built for success.