Investigational HIV Vaccine and Therapy Combination Reduces Time on ART

Barcelona, Spain-based, AELIX Therapeutics, a clinical-stage biotechnology company, announced results this week at CROI for its AELIX-003 study, a phase 2a clinical trial, that met its primary and secondary endpoints for safety, tolerability, and immunogenicity. The study evaluated the company’s HTI T-cell therapeutic HIV vaccine in combination with Gilead’s investigational Toll-Like Receptor 7 (TLR7) agonist, vesatolimod (VES), in people with HIV on antiretroviral therapy.

“These encouraging efficacy data demonstrate that the HTI vaccine in combination with VES may be able to modulate an individual’s HIV-specific immune response in a way that can potentially contribute to a better HIV control in the absence of ongoing ART,” AELIX CSO Christian Brander, PhD, said in a statement. "The AELIX-003 data are exciting, and confirm what we have seen in the AELIX-002 study, where the HTI vaccine alone also extended the time off ART for the vaccinated participants.”

VES is an immune modulator being evaluated as part of an investigational combination regimen that could potentially lead to viral remission.

What the Data Shows

The AELIX-003 study was a randomized, multi-center, placebo-controlled trial to evaluate the safety, immunogenicity, and antiviral efficacy of the MVA. HTI (M)/ChAdOx1.HTI (C) vaccines and VES 6 mg in early-treated PLWH.

Participants on ART were randomized 2:1 to active placebo treatment. During a 24-week ATI, plasma viral load (pVL) was monitored weekly, and ART was resumed if pVL >100,000 copies/mL (c/mL), or >10,000 c/mL for eight consecutive weeks, and/or CD4<350 cells/mL.

According to the investigators, results included the following:

• 50 participants enrolled into the study and 47 entered the ATI period (CCMM+VES (n=30) or placebo (n=17)
• HTI immunizations and VES were well-tolerated with one unrelated SAE
• Currently available immune data demonstrated strong HTI-focused T-cell immunogenicity after vaccination
• The proportion of CCMM+VES participants who remained off ART for 24 weeks was 33% (10/30) compared to 24% (4/17) of placebo participants
• VES increased the production of circulating antiviral cytokines and chemokines.

According to the company, the study also looked at the efficacy of the HTI vaccine in combination with VES to avoid, delay or contain viral rebound compared to a placebo group. Participants underwent an analytical treatment interruption (ATI) in their antiretroviral therapy (ART) for up to 24 weeks. During this time, plasma viral load was monitored weekly.

The data show that a higher proportion of HTI+VES-treated participants remained off ART for the full 24 weeks. The combination of the HTI vaccine and VES as part of an HIV cure strategy in early treated people with HIV was safe and well tolerated.

"The HTI vaccine is aimed at refocusing the immune response to especially vulnerable sites in HIV. The vaccine contains antigenic regions of HIV that are more commonly targeted by individuals who naturally control the virus. Maintenance of viral remission without ART represents the next frontier in HIV infection treatment and an important step towards HIV eradication,” Brander said.