A5386: A Phase 1 Clinical Trial of the Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) with and without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

Scientists are looking for ways to effectively clear HIV that rests in areas of the body where standard antiretroviral treatment (ART) is unable to reach. IL-15 superagonist (N-803) appears to reactivate HIV that is “asleep” and is also thought to increase the body’s natural immune response to HIV. Broadly neutralizing antibodies (bNAbs), such as 10-1074 and VRC07-523LS, have been shown to control growth of HIV in the blood and to increase the body’s immune response to HIV. N-803 alone or in combination with bNAbs may provide greater control of HIV than previous efforts.

This research study is trying to find out if N-803, VRC07-523LS, and 10-1074 are safe and effective at reactivating and targeting the latent cell pool of HIV RNA during an ATI (analytical treatment interruption). All participants will receive eight doses of N-803. Half of participants will also receive 10-1074 and VRC07-523LS. A year after starting study treatment, participants will stop ART for up to 24 weeks to see how well their immune systems control growth of HIV (analytic treatment interruption or ATI).  Participants will be followed closely to see if ART should be restarted. After restarting ART, participants will be followed for another 24 weeks.

Major requirements for entering the study (things that must be true for you):

• Living with HIV.
• Have a low or undetectable viral load for at least 2 years.
• Be willing to take a superagonist and broadly neutralizing antibodies and complete study related tests.
• Agree to use contraception/birth control methods.
• Be between 18 and 70 years old.
• Be willing to temporarily stop taking antiretrovirals or ART.

Events or conditions that would prevent you from participating (things that cannot be true about you):

• Recent serious illness or condition requiring hospitalization.
• Breastfeeding or pregnant.
• Active Hepatitis B or C infection or history of AIDS-defining conditions.
• Current CD4 cell count less than 500 or ever had a CD4 cell count less than 200.

Talk to your study staff for a complete list of inclusion/exclusion criteria.

• Blood and urine tests at scheduled clinic visits for safety evaluations and to check your immune function.
• Leukapheresis (collection of immune cells through a catheter in the vein) (a procedure similar to donating platelets) will be completed twice.
• Lymph node fine-needle aspirate (a type of biopsy using a needle) is an optional procedure which will be done prior to study entry and at Week 13.

• Eight doses of N-803 given by needle under the skin; half of participants will receive two doses of 10-1074 and one dose of VRC07-523LS given intravenously (through a catheter in the vein).

Maximum of 2 years. Arm A will receive one dose of N-803 at Week 1 and then every 3 weeks for a total of eight doses.