Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

Step 1 Inclusion Criteria:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load (VL). More information on this criterion can be found in the protocol.
• Ability and willingness of participant or legal representative to provide informed consent
• Clinically stable on their first or second ART regimen that includes a boosted protease inhibitor or an integrase inhibitor. The current regimen should have been stable for 8 weeks at the time of entry. Changes while the patient HIV viral load was undetectable did not count toward the number of ART regimens used, (for example, an individual switching from a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable would still be on their first regimen).
• HIV-1 RNA that is less than 50 copies/mL using a Food and Drug Administration (FDA)-approved assay performed by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent within 45 days prior to study entry
• HIV-1 RNA less than 50 copies/mL using a FDA-approved assay for at least 24 weeks prior to study entry performed by any laboratory that had a CLIA certification or its equivalent. More information on this criterion can be found in the protocol.
• Screening CD4+ T-cell count greater than or equal to 450 cells/μL within 45 days prior to study entry
• Nadir CD4+ T-cell count greater than 200 cells/μL
• Willingness to have blood samples collected, stored indefinitely, and used for study-related research purposes
• The following laboratory values obtained within 45 days prior to enrollment:
• Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm^3
• Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal to 11.0 g/dL for women
• Platelet count greater than or equal to 100,000/mm^3
• Creatinine clearance greater than or equal to 60 mL/min estimated by the Cockcroft-Gault equation. More information on this criterion can be found in the protocol.
• Alanine aminotransferase (ALT) less than or equal to 2.0 times the upper limit of normal (ULN)
• At least eight participants had availability of plasma or serum specimen before the initiation of ART either in the Center for AIDS Research (CFAR) repository of the University of Pennsylvania, University of Alabama, or in the AIDS Clinical Trials Group (ACTG) central repository
• For females of reproductive potential (i.e., women who have not been post-menopausal for at least 24 consecutive months; who had menses within the preceding 24 months; or women who had not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative urine pregnancy test (with a sensitivity of 15 to 25 mIU/mL) within 48 hours prior to screening and entry. More information on this criterion can be found in the protocol.
• Contraceptive methods were required for female participants of reproductive potential. Female participants of reproductive potential and their male partners MUST HAVE appropriately used at least two contraceptives, with one method being highly effective and the other method being either highly effective or less effective. More information on this criterion, including a list of acceptable contraceptive options, can be found in the protocol.
• Contraceptive methods were required for female partners of reproductive potential of male study participants on study drug. Female partners of reproductive potential of male study participants and/or their male partners MUST HAVE appropriately used at least two contraceptives, with one method being highly effective and the other method being either highly effective or less effective. More information on this criterion, including a list of acceptable contraceptive options, can be found in the protocol.
• Negative hepatitis B surface antigen (HBsAg) result obtained within 6 months prior to study entry
• Hepatitis C virus (HCV) antibody negative result within 6 months prior to entry, or if the HCV antibody result was positive, a negative HCV RNA obtained within 6 months prior to study entry
• Adequate venous access in at least one arm

Step 2 Inclusion Criteria:

• Entry into Step 1 of this study (A5340)
• Receipt of at least one dose or partial dose of VRC01 in Step 1
• Reinitiating ART for protocol or non-protocol-defined reasons. More information on this criterion can be found in the protocol.

Step 3 Inclusion Criteria:

• Entry into and completion of Step 2 of this study (A5340) at least 3 months prior
• HIV-1 RNA less than 50 copies/ml at pre-entry visit
• Ability and willingness of participant or legal representative to provide informed consent
• Willingness to have blood samples/specimens collected, stored indefinitely, and used for study-related research purposes
• Adequate venous access in at least one arm

Step 1 Exclusion Criteria:

• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational
• Weight greater than 115 kg or less than 53 kg
• History of an AIDS-defining illness
• Ongoing AIDS-related opportunistic infection (including oral thrush)
• History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment
• Currently breastfeeding
• Receipt of other investigational study agent within 30 days prior to enrollment
• Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or other immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs]) within 30 days prior to enrollment
• Any other chronic or clinically significant medical condition that in the opinion of investigator would have jeopardized the safety or rights of the participant, including, but not limited to diabetes mellitus type I, OR clinically significant forms of drug or alcohol abuse, severe asthma, autoimmune disease, uncontrolled hypertension, liver disease, psychiatric disorders, heart disease, or cancer
• Treatment during acute infection (i.e., treatment within 6 months of acute infection)
• Current use of a NNRTI

Step 2 Exclusion Criteria:

• Non-participation in Step 1

Step 3 Exclusion Criterion:

• Non-participation in Step 2