HIV/AIDS Awareness Month 2024: Looking Back at Progress in Gene Therapy and Gene Editing

According to HIV.gov, approximately 1.2 million people in the United States are living with HIV, 13% of whom do not know they have the infection. In 2022 alone, around 31,800 people in the US are estimated to have contracted HIV.

Although interest in applying advanced therapeutic modalities like gene therapy and gene editing to the treatment of HIV has been slower compared to some other disease areas, a few companies and institutions are currently making notable efforts. In honor of HIV/AIDS Awareness Month, observed annually in December by the patient and clinician communities, CGTLive® is taking a look back at some of our coverage of gene therapy and gene editing approaches in HIV over the past year. Click the "READ MORE" buttons for more details and information about each item.

CRISPR-Editing EBT-101 Therapy Safe, Temporarily Suppresses HIV Infection

May 21, 2024 — Excision BioTherapeutics’ EBT-101-001 phase 1/2 trial (NCT05144386) of EBT-101 CRISPR-based gene editing therapy has met its primary safety endpoint and its secondary biodistribution/immunogenicity endpoint. Data from the trial were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland by principal investigator Rachel M. Presti, MD, PhD, Professor of Medicine, Washington University School of Medicine, St. Louis.

“Initial data from the EBT-101-001 trial provides important clinical evidence that a gene editing treatment modality can be safely delivered for targeting the HIV DNA reservoirs in human cells. This study provides researchers with invaluable insights for how CRISPR technology can be applied for addressing infectious disease and was an important first step towards additional programs designed to optimize this treatment modality for treating the millions of individuals who are impacted by HIV and other infectious disease,” Presti said in a statement.

Investigators observed no serious adverse events (AEs), grade 1 AEs related to the therapy, and grade 1 or 2 AEs that resolved without treatment. Of the 5 participants who received a single infusion of the initial dose of EBT-101, 3 stopped antiretroviral therapy, experienced viral rebound, and had to restart antiretrovirals. One participant maintained viral suppression for 16 weeks after treatment discontinuation.

Janice Chen, PhD, on Novel Approaches to Gene Editing

May 23, 2024 — Several novel approaches to gene editing were discussed at a session entitled “Advances in genome editing: in vivo small edits and the promise of large insertions” at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. Shortly after the session took place, CGTLive® sat down with Janice Chen, PhD, the cofounder and chief technology officer of Mammoth Biosciences, who served as a cochair of the session, to learn more. Chen gave an overview of the 4 talks in the session, which covered topics including integrase-mediated programmable genomic integration, base editing for neurological disorders, DNA polymerase editors, and results from a clinical trial evaluating a multiplex CRISPR/Cas9 system approach for the treatment of latent HIV.

Marcus Conant, MD, on Investigating Gene Therapy for HIV Suppression

April 3, 2024 — AGT103-T is a gene therapy using miRNA to block 2 HIV-specific genes, the CCR5 receptor and the regulatory TAT protein that facilitates the transcription of viral RNA into mRNA in the host cell. The therapy was originally developed by American Gene Technologies and is now under the purview of its spinout, Addimmune.

CGTLive spoke with Marcus Conant, MD, chief medical officer, Addimmune, who has been caring for patients with HIV since the 1980s, to learn more about AGT103-T and the potential of treating HIV with gene therapy. He discussed results of an early phase 1 trial (NCT04561258) in 7 patients and some promising efficacy signals seen in those participants.

REFEENCE
1. U.S. Statistics. HIV.gov. Website. Accessed December 5, 2024. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics