A5374: A Phase I/IIa Randomized, Placebo-Controlled Trial of Conserved-Mosaic T-cell Vaccine in a Regimen with Vesatolimod and Broadly Neutralizing Antibodies in Adults Initiated on Suppressive Antiretroviral Therapy during Acute HIV-1

Treatment Experienced

Current antiretroviral therapy (ART) does not cure HIV. ART just holds the virus in check so it cannot multiply and destroy the immune system. When most people talk about a cure for HIV, they generally imagine a cure that would remove all virus from the body. However, many researchers are looking for a different approach, known as a functional cure, that would improve the immune system response to HIV so that it controls the virus and allows for longer periods during which a person with HIV could stop taking ART.

 

• To test the safety and tolerability of the experimental products.
• To see if the combination of these products improves the body’s response to HIV in people with HIV who started ART early after infection.

• Started combination ART medications very soon after HIV infection (during acute HIV).
• Have been on stable ART for at least 1 year.
• Have a CD4 count of at least 500 cells and an HIV viral load that is undetectable.
• Be 18 years of age or older.
• Be willing to stop taking ART for a supervised antiretroviral treatment interruption (ATI).
• No history of cancer, HIV-related infections, autoimmune, serious skin, heart, or liver disease.

In Part 1, participants will continue taking their ART and will be randomized to receive either the active study products or inactive placebos in a 2:1 ratio according to the following schedule:

• Week 0 and Week 4: Study vaccines or placebos by injection in both arms.
• Weeks 6-24: Vesatolimod or placebo tablets by mouth, every 2 weeks, totaling 10 doses.
• Week 7: Infusion of bNAbs or placebos into a vein in one arm.
• Week 66: Study vaccine or placebo by injection into one arm.

 

In Part 2, participants will stop taking ART and not receive any study treatment. They will have frequent visits to measure their HIV viral load and CD4 counts.

 

After Part 2, if they need to restart ART (depending on a list of criteria), they will resume taking HIV medications.

• Two different types of study vaccines designed to focus and improve the body’s immune response to HIV.
• A TLR7 agonist, Vesatolimod, that may strengthen the body’s immune response to HIV
• Two different products called broadly neutralizing antibodies or bNAbs (GS-5423 and GS-2872), that attach to the virus and prevent its spread in the body.

Up to approximately 110 weeks depending on the time spent in Part 2 of the study.