Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT03571204
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 3
• Actual Duration (Months): 30.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Background:

Human immunodeficiency virus (HIV) affects the immune system. The main function of the immune system is protect you from infections and other diseases such as cancer. HIV attacks and cripples the immune system making people more susceptible to a variety of infections and cancers. Currently, the standard treatment for HIV infection is a daily administration of anti-HIV drugs. These drugs are called combination antiretroviral therapy (ART). ART is very effective at suppressing HIV, but does not cure HIV infection. ART must be taken continuously for life to be effective. ART can stop being effective if not taken correctly and can cause permanent side effects. Researchers want to see if two new products can control HIV infection without the use of ART. The products are the antibodies 3BNC117 and 10-1074.

Objective:

To see if 3BNC117 and 10-1074 are safe and can control HIV levels in the blood of people who are not taking ART or people who stop taking their ART during the study. .

Eligibility:

Adults ages 18-65 with HIV who are:

• on ART and willing to stop treatment for at least 28 weeks

• OR not taking ART with low levels of HIV in the blood

Design:

Participants will be screened with a physical exam, medical history, and blood, heart, and urine tests.

Participants will get the 2 study products or salt water (placebo). A thin tube will be placed in an arm vein. Each product will be given directly into the vein for about 1 hour.

To help collect blood cells to study in the laboratory, participants may have a procedure known as leukapheresis in which blood will be removed through a needle in the arm. Some of the white blood cells will be separated from the blood and used for research studies to see how 3BNC117 and 10-1074 effects HIV and the immune system. The rest of the blood will be returned to the person through another needle in the arm.

Participants will have 18 study visits over 28 weeks. They will repeat some screening tests. They may have leukapheresis again.

At 8 study visits, participants will get the study products or placebo.

All participants will be followed for at least 24 weeks after their last dose of the study infusions. Participants who are in the Group that stops ART will be monitored closely to make sure the levels of virus in their blood do not go to high. If at any time during this the study a person develops HIV-related symptoms, or if the viral levels go up to high levels for more than 4 weeks, ART will be restarted and no further infusions of 3BNC117 and 10-1074 will be given.

...

Condition or Disease	Intervention/Treatment	Phase
HIV	Biological: 3BNC117 and 10-1074; Biological: Placebo	Phase 1

Detailed Description

Recent advances in antibody cloning technologies have led to the discovery of a number of highly potent and HIV-specific broadly neutralizing monoclonal antibodies (bNAbs) from B cells of HIV-infected individuals. It has been shown that certain bNAbs can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in Simian Immunodeficiency virus (SIV)-infected animals and block cell-to-cell transmission of laboratory-adapted HIV in vitro. In light of these encouraging outcomes, a number of clinical trials have been conducted in recent years in order to explore the feasibility of achieving sustained virologic suppression using a single bNAb in HIV-infected individuals following analytical treatment interruption (ATI). Despite the fact that repeated administration of a single bNAb was safe and well-tolerated, the vast majority of study subjects experienced plasma viral rebound following ATI, clearly demonstrating that successful passive immunotherapy will require different approach, including the use of a combination of 2 or more bNAbs to achieve extended periods of virologic suppression.

Given a major emphasis on current HIV research lies in the possibility of achieving ART-free virologic remission, it is of great interest to investigate whether a combination of potent HIV- specific bNAbs, such as 3BNC117 and 10-1074, can prevent plasma viral rebound in infected individuals upon discontinuation of ART or suppress viral replication in subjects who are not taking ART.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study of Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals
• Actual Study Start Date: Sep 10, 2018
• Actual Primary Completion Date: Mar 29, 2021
• Actual Study Completion Date: Mar 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1: ART prior to 3BNC117 + 10-1074 in HIV-1 subject Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Biological: 3BNC117 and 10-1074; Both 3BNC117 and 10-1074 administered intravenously at 30 mg/kg dose level in 250 ml normal saline for 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The two antibodies will be mixed in separate bags of saline for sequential administration.
Placebo Comparator: Group 1: ART prior to placebo treatment in HIV-1 subject Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Biological: Placebo; Placebo is two separate bags of 250 ml normal saline administered intravenously for 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The two separate bags of placebo are administered sequentially.
Experimental: Group 2: 3BNC117 + 10-1074 in HIV-1 subject Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Biological: 3BNC117 and 10-1074; Both 3BNC117 and 10-1074 administered intravenously at 30 mg/kg dose level in 250 ml normal saline for 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The two antibodies will be mixed in separate bags of saline for sequential administration.

Outcome Measures

Primary Outcome Measures

1. Participants With Grade 3 or Higher Adverse Events [29 months]

   Participants with grade 3 or higher adverse events (AE), including serious adverse advents. AE severity was graded according to the Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1, July, 2017

Secondary Outcome Measures

1. Participants Who Experienced Rebound of Plasma Viremia [28 weeks]

   Difference between the treatment and placebo arms in the number of participants who experienced rebound of plasma viremia and met criteria to restart ART prior to study week 28.

2. Participants Who Achieved Suppression of Viremia [28 weeks]

   Participants who achieved suppression of viremia to <40 copies/ml by study week 28

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

General Inclusion Criteria for both Groups:

1. Age 18-65 years old.

2. HIV-1 infection and clinically stable.

3. General good health and has an identified primary health care provider for medical management of HIV infection and is willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.

4. Cluster of differentiation 4 (CD4)+ T cell count >450 cells/mm(3) at screening.

5. Laboratory values within pre-defined limits at screening:

6. Absolute neutrophil count >1,000/mm(3).

7. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women.

8. Platelet count >100,000/mm(3).

9. Estimated or a measured glomerular filtration rate >60 mL/min/1.73m(2) as determined by the National Institutes of Health (NIH) Clinical Center laboratory.

10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of <2.5 times upper limit of normal (ULN), direct bilirubin within the normal range for the NIH Clinical Center laboratory.

11. Willingness to have samples stored for future research.

Inclusion criteria specific for Group 1:

1. Institution of ART within 12 weeks of being diagnosed with primary HIV-1 infection

2. Primary HIV-1 infection is defined as meeting at least one of the following criteria:

3. Detectable plasma HIV-1 RNA levels of >2000 copies/mL with a negative result from an HIV-1 enzyme immunoassays (EIA), or

4. Positive result from an HIV-1 EIA with a negative or indeterminate result from an HIV-1 western blot or another confirmatory antibody test that subsequently evolves to a confirmed positive result, or

5. Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA levels of >400,000 copies/mL, in the setting of a potential exposure to HIV-1.

6. Negative result from an HIV-1 EIA within 6 months prior to a positive result from an HIV-1 EIA and an HIV-1 western blot or another confirmatory antibody test.

7. Presence of low level of HIV antibodies as determined by having a positive EIA or a positive Western blot with a non-reactive detuned EIA according to a serologic testing algorithm for recent infection.

8. Documentation of continuous ART treatment with suppression of plasma viral level below the limit of detection for greater than or equal to 1 years. Individuals with blips (i.e., detectable viral levels on ART) prior to screening may be included provided they satisfy the following criteria:

9. The blips are <400 copies/mL, and

10. Succeeding viral levels return to levels below the limit of detection on subsequent testing.

11. Willingness to undergo ATI

12. Willingness for both male and female subjects to agree to use barrier protection methods or abstinence during the ATI phase of the study to decrease the risk of HIV transmission.

Inclusion criteria specific for Group 2:

1. No ART within 24 months of screening.

2. HIV plasma viremia between 200 and 5,000 copies/mL at screening AND at least two documented viral level greater than or equal to 200 copies/mL in the 12 months prior to screening.

At the screening visit, subjects considering enrollment in Group 2 will be advised that current guidelines recommend treatment of all individuals with HIV infection regardless of viral levels and CD4 counts.

Reproductive Risks

Contraception: The effects of 3BNC117 and 10-1074 on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate pregnancy prevention. This includes the use an effective method of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting intrauterine device (IUD), hormone-based contraceptive with condom) for the study duration. Subjects should also agree to use a male or female condom while off ART. Pregnancy prevention must be practiced continuously for the duration of study participation. Females of childbearing-age must have a negative pregnancy test result prior to receiving each infusion of 3BNC117/10-1074. During the course of the study, if a female subject, or the partner of a male subject suspects or in fact becomes pregnant, the effected subject should inform the study staff immediately, as well as the woman s primary care physician.

EXCLUSION CRITERIA:

1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen

(HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.

1. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.

2. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.

3. Receipt of other investigational study agent within 28 days of enrollment.

4. Any active malignancy that may require systemic chemotherapy or radiation therapy.

5. Systemic immunosuppressive medications received within 3 months prior to enrollment (Not excluded: [1] corticosteroid nasal spray or inhaler; [2] topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur [length of therapy less than or equal to10 days, with completion in greater than or equal to 30 days prior to enrollment]).

6. History or other clinical evidence of:

7. Significant or unstable cardiac or cerebrovascular disease (e.g., angina, congestive heart failure, recent stroke or myocardial infarction).

8. Severe illness, malignancy, immunodeficiency other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study.

9. Active drug or alcohol use or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.

10. Pregnancy or breast-feeding at time of screening.

11. Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study (Group 1 only).

Co-enrollment Guidelines: Co-enrollment in other trials is restricted to observational studies or those evaluating the use of a licensed medication and is subject to approval of the principal investigator (PI).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Michael C Sneller, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 19, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. Epub 2016 Nov 9.
• Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP Jr, Buckley N, Kremer G, Nogueira L, Braunschweig M, Scheid JF, Horwitz JA, Shimeliovich I, Ben-Avraham S, Witmer-Pack M, Platten M, Lehmann C, Burke LA, Hawthorne T, Gorelick RJ, Walker BD, Keler T, Gulick RM, Fätkenheuer G, Schlesinger SJ, Nussenzweig MC. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015 Jun 25;522(7557):487-91. doi: 10.1038/nature14411. Epub 2015 Apr 8. Erratum in: Nature. 2016 Jul 28;535(7613):580.
• Caskey M, Schoofs T, Gruell H, Settler A, Karagounis T, Kreider EF, Murrell B, Pfeifer N, Nogueira L, Oliveira TY, Learn GH, Cohen YZ, Lehmann C, Gillor D, Shimeliovich I, Unson-O'Brien C, Weiland D, Robles A, Kümmerle T, Wyen C, Levin R, Witmer-Pack M, Eren K, Ignacio C, Kiss S, West AP Jr, Mouquet H, Zingman BS, Gulick RM, Keler T, Bjorkman PJ, Seaman MS, Hahn BH, Fätkenheuer G, Schlesinger SJ, Nussenzweig MC, Klein F. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat Med. 2017 Feb;23(2):185-191. doi: 10.1038/nm.4268. Epub 2017 Jan 16.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03571204
• Other Study ID Numbers: 180115; 18-I-0115
• First Posted: Jun 27, 2018
• Last Update Posted: Feb 9, 2022
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Treatment Interruption; Neutralizing Monoclonal Antibody

Study Results

Participant Flow

Pre-assignment Detail	of 27 participants consented, 6 participants were screen failure so did not start the actual study.

Arm/Group Title	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject	Group 1: ART Prior to Placebo Treatment in HIV-1 Subject	Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
Arm/Group Description	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
Period Title: Overall Study
STARTED	8	8	5
COMPLETED	7	6	5
NOT COMPLETED	1	2	0

Baseline Characteristics

Arm/Group Title	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject	Group 1: ART Prior to Placebo Treatment in HIV-1 Subject	Group 2: 3BNC117 + 10-1074 in HIV-1 Subject	Total
Arm/Group Description	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Total of all reporting groups
Overall Participants	8	8	5	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	5 100%	21 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	8 100%	8 100%	5 100%	21 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%	2 25%	0 0%	3 14.3%
Not Hispanic or Latino	7 87.5%	6 75%	5 100%	18 85.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 25%	1 12.5%	0 0%	3 14.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 12.5%	0 0%	1 20%	2 9.5%
White	4 50%	7 87.5%	3 60%	14 66.7%
More than one race	1 12.5%	0 0%	1 20%	2 9.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Participants With Grade 3 or Higher Adverse Events
Description	Participants with grade 3 or higher adverse events (AE), including serious adverse advents. AE severity was graded according to the Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1, July, 2017
Time Frame	29 months

Outcome Measure Data

Analysis Population Description

Participants who started the study

Arm/Group Title	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject	Group 1: ART Prior to Placebo Treatment in HIV-1 Subject	Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
Arm/Group Description	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
Measure Participants	8	8	5
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Participants Who Experienced Rebound of Plasma Viremia
Description	Difference between the treatment and placebo arms in the number of participants who experienced rebound of plasma viremia and met criteria to restart ART prior to study week 28.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Participants who initiated anti-retroviral treatment interruption (ATI). Two participants did not participate in ATI. One participant deviated from the protocol and was lost to follow-up.

Arm/Group Title	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject	Group 1: ART Prior to Placebo Treatment in HIV-1 Subject
Arm/Group Description	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
Measure Participants	7	7
Count of Participants [Participants]	0 0%	6 75%

3. Secondary Outcome

Title	Participants Who Achieved Suppression of Viremia
Description	Participants who achieved suppression of viremia to <40 copies/ml by study week 28
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Participants who started intravenous infusion therapy

Arm/Group Title	Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
Arm/Group Description	Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
Measure Participants	5
Count of Participants [Participants]	2 25%

Adverse Events

Time Frame	29 months
Arm/Group Title	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject		Group 1: ART Prior to Placebo Treatment in HIV-1 Subject		Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
Arm/Group Description	Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.		Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.		Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.
All Cause Mortality
	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject		Group 1: ART Prior to Placebo Treatment in HIV-1 Subject		Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/5 (0%)
Serious Adverse Events
	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject		Group 1: ART Prior to Placebo Treatment in HIV-1 Subject		Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		1/5 (20%)
Infections and infestations
Arthritis bacterial	0/8 (0%)		0/8 (0%)		1/5 (20%)
Other (Not Including Serious) Adverse Events
	Group 1: ART Prior to 3BNC117 + 10-1074 in HIV-1 Subject		Group 1: ART Prior to Placebo Treatment in HIV-1 Subject		Group 2: 3BNC117 + 10-1074 in HIV-1 Subject
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		8/8 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Lymph node pain	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Neutrophilia	0/8 (0%)		0/8 (0%)		1/5 (20%)
Eye disorders
Chalazion	0/8 (0%)		1/8 (12.5%)		1/5 (20%)
Conjunctivitis allergic	0/8 (0%)		0/8 (0%)		1/5 (20%)
Vision blurred	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Gastrointestinal disorders
Haemorrhoids	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Tooth disorder	0/8 (0%)		0/8 (0%)		1/5 (20%)
General disorders
Chills	2/8 (25%)		0/8 (0%)		1/5 (20%)
Fatigue	0/8 (0%)		0/8 (0%)		1/5 (20%)
Infusion site extravasation	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Pain	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Pyrexia	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Infections and infestations
Abscess oral	0/8 (0%)		0/8 (0%)		1/5 (20%)
Acute sinusitis	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Bronchitis	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Chlamydial infection	1/8 (12.5%)		1/8 (12.5%)		0/5 (0%)
Clostridium difficile infection	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Gastroenteritis	0/8 (0%)		2/8 (25%)		0/5 (0%)
Nasopharyngitis	3/8 (37.5%)		2/8 (25%)		1/5 (20%)
Pharyngitis streptococcal	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Rash pustular	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Upper respiratory tract infection	1/8 (12.5%)		2/8 (25%)		0/5 (0%)
Investigations
Alanine aminotransferase increased	2/8 (25%)		1/8 (12.5%)		0/5 (0%)
Amylase increased	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Aspartate aminotransferase increased	2/8 (25%)		1/8 (12.5%)		0/5 (0%)
Blood bicarbonate decreased	0/8 (0%)		2/8 (25%)		1/5 (20%)
Blood bilirubin increased	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Blood calcium decreased	0/8 (0%)		0/8 (0%)		1/5 (20%)
Blood creatine phosphokinase increased	1/8 (12.5%)		1/8 (12.5%)		0/5 (0%)
Blood creatinine increased	1/8 (12.5%)		1/8 (12.5%)		0/5 (0%)
Blood glucose increased	6/8 (75%)		1/8 (12.5%)		3/5 (60%)
Blood lactate dehydrogenase increased	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Blood phosphorus decreased	4/8 (50%)		2/8 (25%)		0/5 (0%)
Blood potassium decreased	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Blood sodium decreased	0/8 (0%)		0/8 (0%)		2/5 (40%)
Haemoglobin decreased	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Neutrophil count decreased	0/8 (0%)		0/8 (0%)		1/5 (20%)
Musculoskeletal and connective tissue disorders
Back pain	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Myalgia	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Nervous system disorders
Headache	1/8 (12.5%)		1/8 (12.5%)		1/5 (20%)
Syncope	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Psychiatric disorders
Anxiety	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		0/8 (0%)		1/5 (20%)
Nasal congestion	0/8 (0%)		0/8 (0%)		1/5 (20%)
Oropharyngeal pain	1/8 (12.5%)		0/8 (0%)		0/5 (0%)
Sinus congestion	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)		1/8 (12.5%)		0/5 (0%)
Rash pruritic	0/8 (0%)		0/8 (0%)		1/5 (20%)

Limitations/Caveats

The study was terminated early due the the COVID-19 pandemic. The pre-defined samples size of 30 participants (15 per arm) for Group 1 was not not reached prior to closing the protocol.

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.