Safety and Therapeutic Efficacy of the VRC01 Antibody in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection

Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific Monoclonal Antibody VRC01 During Analytic Treatment Interruption in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection

The study will evaluate the safety and therapeutic efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01), when administered during analytic treatment interruption (ATI), in adults who began antiretroviral therapy (ART) during early acute HIV infection.

Human monoclonal antibodies (mAbs) may have the potential to treat HIV infection by preventing the spread of the virus. This study will evaluate an experimental mAb known as VRC-HIVMAB060-00-AB (VRC01). The purpose of this study is to evaluate the safety and therapeutic efficacy of VRC01, when administered during analytic treatment interruption (ATI), in adults who began antiretroviral therapy (ART) during early acute HIV infection.

The study will enroll participants from the RV 254 study who were diagnosed during early acute HIV infection and who have been on ART. At study entry, participants will stop taking their antiretroviral (ARV) medications. They will be randomly assigned to receive an intravenous (IV) infusion of VRC01 or placebo at Weeks 0 (study entry), 3, 6, 9, 12, 15, 18, 21, and 24. For 7 days following each infusion, participants will be asked to record and report any symptoms to study researchers.

In addition to the infusion visits, participants will attend follow-up visits for 48 weeks. Study visits may include physical examinations, blood collection, and urine collection. Neurocognitive testing will take place at select study visits. Some participants may take part in optional study procedures including mucosal secretion collection, MRI brain scan, colon biopsy, lymph node biopsy, leukapheresis, and lumbar puncture.

Study staff will monitor participants' HIV throughout the study, and participants will end their participation in the study and restart their ARV medications, if needed.

Inclusion Criteria:

• Able and willing to provide written informed consent or, in the case of illiteracy, witnessed verbal informed consent with documentation of a thumbprint in lieu of a signature.
• Passes Test of Understanding.
• Man or woman aged 20-50 years.
• Initiated on ART during acute HIV infection (Fiebig Stage I to III at RV 254 enrollment).
• Prescribed ART for at least 24 months prior to enrollment.
• HIV-1 RNA less than 50 copies/mL on at least three consecutive measurements within the past 12 months.
• Integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) below the level of detection (1 copy/10^5 PBMCs) within 6 months prior to enrollment.
• Last documented peripheral blood CD4 greater than 400 cells/mm^3 within 3 months prior to enrollment.
• No HIV-related or AIDS-defining illness within 6 months prior to enrollment.
• In general good health.
• Able to participate in study visits.

Female-Specific Criteria:

• Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman is sexually active and has no history of hysterectomy or tubal ligation or menopause, she must agree to use a prescription birth control method or a barrier birth control method.
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment for any women unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy.

Exclusion Criteria:

• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.
• Ongoing AIDS-related opportunistic infection (including oral thrush).
• Active injection drug use within previous 12 months.
• History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment.
• History of chronic urticaria requiring daily treatment.
• Physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, or focal neurologic deficit.
• Hypertension that is not well controlled by medication.
• Hepatitis B surface antigen positive at any time in the past.
• Hepatitis C antibody positive at any time in the past.
• Untreated syphilis.
• Estimated glomerular filtration rate (GFR) less than 50 ml/min within the past 90 days.
• Pregnant or breastfeeding.
• Receipt of licensed vaccine or other investigational study agent within 28 days prior to enrollment or past participation in an investigational HIV vaccine study with receipt of active product.
• Current or planned participation in another interventional clinical trial during the study period.
• Chronic or recurrent use of medications that modify host immune response, e.g., oral or parenteral steroids, cancer chemotherapy.
• Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.
• Study site employee.