Drug Database: 3BNC117

Pharmacology

Pharmacology

Mechanism of Action

Broadly neutralizing antibody (bNAb). 3BNC117 is a recombinant human IgG1 kappa monoclonal antibody cloned from an HIV-infected viremic controller. It is a second-generation bNAb that targets the CD4 binding site on HIV envelope gp160.^5,6

Second-generation HIV bNAbs are naturally occurring antibodies with potent neutralizing activity against a broad array of HIV strains. The utility of bNAbs is being researched for both HIV prevention and treatment/cure. By binding to sites on HIV envelope and through Fc receptor interactions, bNAbs can potentially 1) inhibit cell-free and cell-to-cell viral entry, 2) induce cellular phagocytosis and destruction by macrophages or antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, and 3) promote the maturation and activity of dendritic cells.^5,7–9 Because it is difficult to induce in vivo generation of bNAbs using conventional vaccination techniques, bNAbs may need to be given by passive transfer, whereby a bNAb is directly administered to an individual.^5,10

3BNC117 and long-acting versions of 3BNC117 (known as 3BNC117-LS [teropavimab; GS-5423] and 3BNC117-LS-J) are being developed for HIV prevention and/or as a possible component to HIV treatment or cure.^2,4 

Half-life (T_½)

A Phase 1 study (NCT02018510) investigated a single intravenous (IV) infusion of 3BNC117 at four different dose levels (1, 3, 10, and 30 mg/kg) in adults with and without HIV and found that the average half-life of 3BNC117 was approximately 9 days in the HIV-infected group and 17 days in the HIV-uninfected group.¹⁰ In a Phase 2a trial (NCT02446847) of multiple IV infusions of 3BNC117 (30 mg/kg) in adults with HIV, the half-life of 3BNC117 ranged from 14.1 days in adults receiving four doses of 3BNC117 to 19.6 days in adults receiving two doses of 3BNC117.⁶

The half-life of 3BNC117-LS relative to 3BNC117 was measured in a study of macaques administered single IV infusions. 3BNC117-LS was found to have a median half-life of 2.8 weeks, an increase of 2.0-fold when compared to the half-life of 3BNC117 (median 1.4 weeks).¹¹

Resistance

HIV has developed resistance to 3BNC117 in both a Phase 1 (NCT02018510) and 2a (NCT02446847) trial of 3BNC117.^6,10 In the Phase 1 study, high-level resistance to 3BNC117 developed in some, although not all, participants by 28 days after a single 3BNC117 dose.¹⁰

In the Phase 2a study, eight out of 13 participants with HIV had rebound viruses that were more resistant to 3BNC117 when compared to pre-infusion viruses. In the majority of participants, viral rebound occurred at high 3BNC117 concentrations. Of eight participants who had sequence analysis performed on rebound viruses, six participants had viral genotypes indicating resistance to 3BNC117. Notably, five out of eight participants had rebound viruses that appeared to arise from a single reactivated virus from the latent reservoir. In all but two participants, rebound viruses did not demonstrate increased resistance to the investigational bNAb 10-1074.⁶

A Phase 2 study (GS-US-536-5939; NCT05729568) evaluated the long-acting bNAbs teropavimab (GS-5423; 3BNC117-LS) and zinlirvimab (GS-2872; 10-1074-LS) in combination with lenacapavir administered every 6 months (n = 53) versus continued daily oral ART (n = 27). One participant receiving bNAbs plus lenacapavir experienced virologic failure and was found to have lenacapavir concentrations below mean levels. Resistance to lenacapavir developed (Q67H capsid mutation), along with loss of susceptibility to zinlirvimab.¹²

Select Clinical Trials

Select Clinical Trials

Study Identifier: NCT02588586

Sponsor: Rockefeller University
Phase: 2 
Status: This study has been completed.
Study Purpose: The purpose of this open-label study was to evaluate the safety of 3BNC117 and its ability to delay or prevent viral rebound during an analytical treatment interruption (ATI) of ART.
Study Population:

• Participants were adults with HIV who had HIV RNA <50 copies/mL for at least 12 months while on ART and had HIV RNA <20 copies/mL at screening.
• Participants had CD4 counts >500 cells/mm³ and nadir CD4 counts >200 cells/mm³.¹³

Selected Study Results: Results published in J Exp Med (2018) showed that infusions of 3BNC117 in 15 participants was generally well tolerated and resulted in 29 adverse events (AEs) that were possibly related to 3BNC117. The average time to viral rebound following an ATI of ART was 5.5 weeks, which represents a significant delay as compared to viral rebound data from previous studies.¹⁴

Study Identifier: NCT02446847

Sponsor: Rockefeller University
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this open-label, dose-escalation study was to evaluate the safety and pharmacokinetics of 3BNC117 and its ability to delay or prevent viral rebound during an ATI of ART.
Study Population:

• Participants were adults with HIV who had HIV RNA <50 copies/mL for at least 12 months while on ART and had HIV RNA <20 copies/mL at screening.
• Participants had CD4 counts >500 cells/mm³ and nadir CD4 counts ≥200 cells/mm³.
• Participants had 3BNC117-sensitive viruses.^6,15

Selected Study Results: Results published in Nature (2016) showed that 3BNC117 was safe and well tolerated. 3BNC117 was effective in delaying viral rebound following an ATI of ART.⁶

Study Identifiers: ROADMAP; NCT02850016

Sponsor: Rockefeller University
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this open-label study was to compare the efficacy of the latency-reversing agent romidepsin plus 3BNC117 to the efficacy of romidepsin alone on delaying or preventing viral rebound during an ATI of ART.
Study Population:

• Participants were adults with HIV who had been on ART for at least 18 months.
• Participants on a PI- or NNRTI-based ART regimen or on a cobicistat-containing regimen were willing to switch to an INI-based regimen prior to enrollment.
• Participants had HIV RNA <50 copies/mL for at least 12 months and had CD4 counts >500 cells/mm³ at screening.^16,17

Selected Study Results: Results published in The Lancet Microbe (2022) showed that romidepsin plus 3BNC117 and romidepsin administered alone had no substantial effect on reducing latent HIV reservoir size in participants on suppressive ART. Additionally, romidepsin plus 3BNC117, compared to romidepsin administered alone, was not effective in delaying the time to viral rebound during ATI. The observed time to viral rebound was not clinically meaningful in either group.¹⁷

Study Identifiers: eCLEAR; NCT03041012

Sponsor: Aarhus University Hospital
Phase: 1b/2a 
Status: This study has been completed.
Study Purpose: The purpose of this open-label study was to evaluate whether the early administration of romidepsin and/or 3BNC117 in treatment-naive individuals who were initiating ART could reduce the time to viral suppression, limit the size of the latent HIV reservoir, and delay the time to viral rebound during an ATI of ART.
Study Population:

• Participants were newly diagnosed treatment-naive adults with HIV.
• Participants had CD4 counts >200 cells/mm³ at screening.^2,18,19

Selected Study Results: Results presented at CROI 2022 and published in Nature Medicine (2022) showed that the early administration of 3BNC117, with or without romidepsin, led to faster viral load decline and significantly enhanced the elimination of infected cells after ART initiation, as compared to what was observed in participants receiving ART only. After 1 year, latent HIV reservoir size was reduced from baseline in all treatment groups, with the greatest reduction seen in those receiving 3BNC117 plus ART. Among participants who had 3BNC117-sensitive virus, 80% maintained viral control during treatment interruption of ART. In contrast, among participants who had 3BNC117-resistant virus or did not receive 3BNC117, only 20% maintained viral control during treatment interruption.^19,20

Study Identifiers: TITAN; NCT03837756

Sponsor: University of Aarhus
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this study was to evaluate the safety of the TLR9 agonist lefitolimod plus the bNAbs 3BNC117 and 10-1074 and to evaluate whether this combination could delay the time to viral rebound during an ATI of ART.
Study Population:

• Participants were adults with HIV who had been on ART for at least 18 months.
• Participants have had HIV RNA <50 copies/mL for at least 15 months and had CD4 counts >500 cells/mm³ at screening.
• Participants had HIV that was sensitive to 3BNC117 and 10-1074.²¹

Selected Study Results: Results published in Nature Medicine (2023) and presented at CROI 2023 showed that the groups receiving dual bNAb treatment had a significant delay in the time to viral rebound during ART interruption, as compared to groups receiving placebos only or lefitolimod plus placebo. The addition of lefitolimod to dual bNAb treatment did not confer any additional effect on viral control compared to dual bNAb treatment alone.^22,23

Study Identifier: NCT03719664

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to determine an optimal dosage of 3BNC117 and the HIV fusion inhibitor albuvirtide and evaluate the safety and efficacy of this combination as long-acting maintenance treatment.
Study Population:

• Participants are adults with HIV who have been receiving oral ART for the last 24 weeks.
• Participants have been on a stable ART regimen for the past 4 weeks prior to screening and during the time between the screening visit and first treatment visit.
• Participants have at least two alternative antiretroviral drug options available.
• Participants have had HIV RNA <50 copies/mL within the 24 weeks prior to screening and at screening.
• Participants have CD4 counts >300 cells/mm³ at screening.²⁴

Study Identifiers: RIO; NCT04319367

Sponsor: Imperial College London
Phase: 2
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to determine whether the combination of the two long-acting bNAbs 3BNC117-LS and 10-1074-LS can prevent viral rebound during an ATI of ART.
Study Population:

• Participants are adults with HIV who had either started ART within 6 months of the estimated time of primary HIV infection and have nadir CD4 counts >250 cells/mm³ or started ART during the early stage of infection and have nadir CD4 counts >500 cells/mm³.
• Participants have been receiving continuous suppressive ART for at least 1 year and are on an INSTI- or boosted PI-based regimen at the time of randomization.
• Participants have current CD4 counts >500 cells/mm³ or CD4:CD8 ratios >1.
• Participants show no evidence of resistance to 10-1074.^25,26

Selected Study Results: Results presented at CROI 2025 showed that the combination of 3BNC117-LS and 10-1074-LS was significantly more effective than placebo in maintaining viral control in participants who had interrupted ART for up to 20 weeks. At Week 20, 75% of the participants who received bNAbs versus 8.8% of the participants who received placebo had not experienced viral rebound.²⁶
Additional Published Material:

• CROI, 2025: Sustained T cell-mediated immunity after LS-bNAbs in the RIO trial: a vaccinal effect

Study Identifier: NCT04819347

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to evaluate the safety of combination therapy with albuvirtide plus 3BNC117 and determine whether this combination can control viral load levels during an ATI of ART.
Study Population:

• Participants are adults with HIV on a stable ART regimen who initiated ART either within 6 months of primary HIV infection (cohort 1) or after 6 months of primary HIV infection (cohort 2).
• Participants have had HIV RNA <50 copies/mL for at least 12 months prior to screening and have HIV RNA <20 copies/mL at screening.
• Participants have CD4 counts >500 cells/mm³.²⁷

Study Identifier: NCT04560569

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to evaluate the safety and efficacy of combination therapy with albuvirtide plus 3BNC117 in participants with multidrug-resistant HIV. 
Study Population:

• Participants are adults with HIV who have received ART for at least 6 months. Participants have been on a failing ART regimen for at least 8 weeks prior to screening or had treatment failure within the past 8 weeks of screening and are off therapy.
• Participants have HIV that is resistant to at least one ARV drug from at least three different ARV drug classes and have difficulty in constructing a viable suppressive regimen. Participants must have at least one potential approved ARV drug available which can be used as part of an optimized background regimen.
• Participants have had HIV RNA >200 copies/mL within the last 3 months prior to screening and have HIV RNA ≥1,000 copies/mL at screening.²⁸

Study Identifiers: RHIVIERA-02; NCT05300035

Sponsor: ANRS, Emerging Infectious Diseases
Phase: 2
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to evaluate the efficacy of the long-acting bNAbs 3BNC117-LS and 10-1074-LS in controlling viral load levels during an ATI of ART.
Study Population: Participants are adults with primary HIV infection who are initiating ART.²⁹

Study Identifiers: A5374; NCT06071767

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 1/2a
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is the evaluate the safety and efficacy of a combination regimen in adults who initiated suppressive ART during acute HIV infection. The combination regimen contains (1) ChAdV- and MVA-vectored conserved mosaic T-cell vaccines, (2) vesatolimod, and (3) broadly neutralizing antibodies 3BNC117-LS (GS-5423) and 10-1074-LS (GS-2872).
Study Population:

• Participants are adults with HIV who initiated ART within 28 days of acute HIV diagnosis and who have not interrupted ART for more than 14 consecutive days since initiation of ART.
• Participants have been receiving ART with an INSTI-based regimen with two NRTIs or a dolutegravir/lamivudine regimen for at least 6 weeks prior to study entry.
• Participants have HIV RNA <50 copies/mL since initial viral suppression on ART and for at least 1 year and within 60 days prior to study entry.
• Participants have CD4 counts ≥500 cells/mm³ within 60 days of study entry.³⁰

Study Identifiers: GS-US-536-5939; NCT05729568

Sponsor: Gilead Sciences
Phase: 2
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label study is to evaluate the safety and efficacy of the bNAbs teropavimab (GS-5423; 3BNC117-LS) and zinlirvimab (GS-2872; 10-1074-LS) in combination with the capsid inhibitor lenacapavir as long-acting treatment.
Study Population: 

• Participants are adults with HIV who have been receiving a stable oral ART regimen consisting of no more than two drug classes (with the exception of pharmacokinetic enhancers) for at least 1 year.
• Participants have had HIV RNA <50 copies/mL for at least 12 months prior to screening and at screening.
• Participants have CD4 counts ≥200 cells/mm³ at screening.
• Participants have no previous resistance to their current ART regimen, except for isolated NRTI mutations, and have phenotypic sensitivity to both teropavimab and zinlirvimab.³¹

Selected Study Results: Results presented at CROI 2025 showed that teropavimab and zinlirvimab plus lenacapavir administered every 6 months had comparable efficacy to daily oral ART in controlling viral load levels. At Week 26, 96% of participants in each group maintained viral suppression.¹²

Study Identifiers: ACACIA Study; ACTG A5417; NCT06205602

Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Phase: 2
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to evaluate the safety of the long-acting bNAbs 3BNC117-LS and 10-1074-LS and determine whether the combination of the two bNAbs can prevent viral rebound during an ATI of ART.
Study Population: 

• Participants are treatment-naive adults with HIV in Sub-Saharan Africa.
• Participants have HIV RNA >1,000 copies/mL and CD4 counts >200 cells/mm³.³²

Additional studies evaluating 3BNC117 for HIV treatment have been or are being conducted, including the following early-phase trials:

• NCT03526848: A Phase 1b study that evaluated whether 3BNC117 and 10-1074 could control viral rebound in adults with HIV during a treatment interruption of ART. This study has been completed and results are available from Nature (2022).³³
• NCT04250636: A Phase 1 study that evaluated the safety, pharmacokinetics, and antiviral activity of single infusions of both 3BNC117-LS and 10-1074-LS in adults with HIV who were off ART. This study has been completed and results are available from CROI 2022.³⁴
• BEAT-2 (NCT03588715): A Phase 1 study that evaluated whether peginterferon alfa-2b plus 3BNC117 and 10-1074 could control viral rebound and reduce the latent HIV reservoir in adults with HIV during an ATI of ART. This study has been completed, and primary outcome results are available from CROI 2023.^2,35
• NCT04811040: A Phase 1b study that evaluated the safety and efficacy of 3BNC117-LS (teropavimab) and 10-1074-LS (zinlirvimab) in combination with the capsid inhibitor lenacapavir in controlling viral load levels in virologically suppressed adults with HIV. This study has been completed, and results are available from The Lancet HIV (2024), CROI 2024, and HIV Glasgow 2024.³⁶
• MCA-1031 (ES38918) (NCT05245292): A Phase 1 trial evaluating the safety and antiviral activity of 3BNC117-LS and 10-1074-LS in combination with N-803 (an IL-15 superagonist complex) in virologically suppressed adults with HIV during an ATI of ART. This study is ongoing, but not recruiting participants.³⁷
• NCT05612178: A Phase 1 trial evaluating the safety and virologic activity of the combination of 3BNC117-LS plus 10-1074-LS on persistent viral reservoirs in people with HIV on suppressive ART. This study is currently recruiting participants.³⁸
• ACTG A5416 (NCT06031272): A Phase 1 study evaluating the safety and antiviral activity of 3BNC117-LS-J and 10-1074-LS-J in virologically suppressed adults with HIV undergoing an ATI of ART. This study is currently recruiting partcipants.³⁹

Adverse Events

Adverse Events

NCT02588586

In this Phase 2 study, 15 participants with HIV received multiple infusions of 3BNC117. Eighty-seven AEs were reported, 29 of which were considered possibly related to 3BNC117. The majority of the AEs possibly related to 3BNC117 infusions were mild or moderate, and one (elevated bilirubin) was severe. The most common AEs possibly related to 3BNC117 were malaise/fatigue, nausea, and dizziness. During the ATI, CD4 counts were noted to have transiently declined in many participants.¹⁴ 

NCT02446847

In this Phase 2a trial investigating multiple infusions of 3BNC117 in 13 individuals with HIV, most adverse events (AEs) that occurred during the study were transient and mild. Some participants experienced modest drops in CD4 counts during viral rebound, but most had their counts return to baseline by Week 12. Acute retroviral syndrome was not reported in any participants during rebound.⁶

ROADMAP (NCT02850016)

In this Phase 2a trial, 11 participants received romidepsin plus 3BNC117 and nine participants received romidepsin alone. All participants in both groups experienced AEs, most of which were mild to moderate in severity. Out of 267 reported AEs, 39 were considered drug-related and 159 were deemed at least possibly related to study treatments. Two severe AEs occurred in the romidepsin only group, one of which was related to romidepsin and resolved without intervention — increased direct bilirubin. The most common AEs associated with romidepsin were nausea, headache, chills, and vomiting. More drug-related AEs occurred with romidepsin than with 3BNC117. Transient QTc interval prolongation without associated clinical symptoms was seen in three participants one day after romidepsin infusion.¹⁷

eCLEAR (NCT03041012)

In the Phase 1b/2a eCLEAR study, treatment-naive participants received ART only (n = 15); ART plus 3BNC117 (n = 14); ART plus romidepsin (n = 12); or a combination of ART, 3BNC117, and romidepsin (n = 14). Out of 319 reported AEs, 205 were considered unrelated to study treatment. Twenty-nine AEs, most of which were mild, were related to 3BNC117. The most common 3BNC117-related AEs were fatigue and headache. Eighty-five AEs were related to romidepsin, of which 13 were Grade 2 in intensity. The most common romidepsin-related AEs were nausea and fatigue. Six SAEs were reported, but none were related to 3BNC117 or romidepsin.²⁰

TITAN (NCT03837756)

In this Phase 2a trial, participants were randomized to receive placebo/placebo (n=10), lefitolimod/placebo (n=10), placebo/bNAbs (n=11), or lefitolimod/bNAbs (n=12). Out of 253 reported AEs, 94 were considered unrelated to any investigational drug or placebo. Eighty-one AEs, most of which were mild in intensity, were related to lefitolimod. The most common lefitolimod-related AEs were injection site reaction (n = 39) and fatigue (n = 6). Fourteen AEs were related to bNAb therapy — 11 were mild, two were moderate, and one was severe. The severe bNAb-related AE was an infusion-related reaction to 3BNC117 that resolved with treatment. The most common AE related to bNAb therapy was fatigue (n = 5).²²

RIO (NCT04319367)

In the Phase 2 RIO trial, participants were randomized to receive either up to two infusions of the bNAbs 3BNC117-LS and 10-1074-LS (n = 34) or placebo (n = 34). No serious adverse events (SAEs) related to the bNAbs or ART interruption were reported. None of the participants developed anti-bNAb antibodies.²⁶

GS-US-536-5939 (NCT05729568)

In this Phase 2 study, participants either received the bNAbs teropavimab (GS-5423; 3BNC117-LS) and zinlirvimab (GS-2872; 10-1074-LS) in combination with lenacapavir administered every 6 months (n = 53) or continued daily oral ART (n = 27). Treatment-related AEs, excluding ISRs, occurred in six participants (11.3%) in the bNAbs/lenacapavir group and included increased lacrimation, device dislocation, abnormal dreams, and insomnia. There were no Grade 3 or higher treatment-related AEs or serious AEs associated with the bNAbs/lenacapavir regimen. Overall, the most common AEs were mild to moderate ISRs related to subcutaneous lenacapavir injections. No participants discontinued treatment because of an ISR, and there were no infusion-related reactions to either teropavimab or zinlirvimab. Anti-drug antibodies against teropavimab and zinlirvimab developed in six and nine participants, respectively; however, the anti-drug antibodies appeared to have no effect on the pharmacokinetics and safety of the drugs.¹²

Drug Interactions

Drug Interactions

Drug-drug interactions associated with 3BNC117 are currently unknown.

References

References

1. National Center for Biotechnology Information. PubChem substance record for SID 381127297, 3BNC117, Source: ChemIDplus. Accessed April 1, 2025
2. Treatment Action Group website. Research toward a cure trials. Accessed April 1, 2025
3. Gilead Sciences: press release, dated January 9, 2020. Gilead Sciences licenses portfolio of HIV antibodies from The Rockefeller University. Accessed April 1, 2025
4. Jefferys R. The HIV vaccines and passive immunization pipeline report 2024. Treatment Action Group Pipeline Report 2024. Accessed April 1, 2025
5. Halper-Stromberg A, Nussenzweig MC. Towards HIV-1 remission: potential roles for broadly neutralizing antibodies. J Clin Invest. 126(2):415-423. Accessed April 1, 2025
6. Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535(7613):556-560. Accessed April 1, 2025
7. Bruel T, Guivel-Benhassine F, Amraoui S, et al. Elimination of HIV-1-infected cells by broadly neutralizing antibodies. Nat Commun. 2016;7:10844. Accessed April 1, 2025
8. Stephenson KE, Barouch DH. Broadly neutralizing antibodies for HIV eradication. Curr HIV/AIDS Rep. 2016;13:31-37. Accessed April 1, 2025
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10. Caskey M, Klein F, Lorenzi JC, et al. 3BNC117 a broadly neutralizing antibody suppresses viremia in HIV-1-infected humans. Nature. 2015;522(7557):487-491. Accessed April 1, 2025
11. Gautam R, Nishimura Y, Gaughan N, et al. A single injection of crystallizable fragment domain-modified antibodies elicits durable protection from SHIV infection. Nat Med. 2018;24(5):610-616. Accessed April 1, 2025
12. Ogbuagu O, Gaur A, McMahon JH, et al. Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: Phase 2 Week 26 primary outcome. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 9-12, 2025; San Francisco, CA. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed April 1, 2025
13. Rockefeller University. An open label, Phase 2 study of the safety and antiretroviral activity of 3BNC117 in HIV-infected individuals on combination antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 26, 2015. NLM Identifier: NCT02588586. Accessed April 1, 2025
14. Cohen YZ, Lorenzi JCC, Krassnig L, et al. Relationship between latent and rebound viruses in a clinical trial of anti–HIV-1 antibody 3BNC117. J Exp Med. 2018;215(9):2311-2324. doi:10.1084/jem.20180936. Accessed April 1, 2025
15. Rockefeller University. A Phase 2, open label study of the safety, antiretroviral activity and pharmacokinetics of 3BNC117 during a short analytical treatment interruption in HIV-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 17, 2015. NLM Identifier: NCT02446847. Accessed April 1, 2025
16. Rockefeller University. A Phase 2a, randomized study of romidepsin with or without 3BNC117 to evaluate the effects on the HIV-1 reservoir (ROADMAP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02850016. Accessed April 1, 2025
17. Gruell H, Gunst JD, Cohen YZ, et al. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. Lancet Microbe. 2022;3(3):e203-e214. doi:10.1016/S2666-5247(21)00239-1. Accessed April 1, 2025
18. Aarhus University Hospital. Early administration of latency reversing therapy and broadly neutralizing antibodies to limit the establishment of the HIV-1 reservoir during initiation of antiretroviral treatment - a randomized controlled trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 20, 2017. NLM Identifier: NCT03041012. Accessed April 1, 2025
19. Gunst JD, Pahus MH, Rosás-Umbert M, et al. The impact of 3BNC117 and romidepsin treatment at ART initiation on HIV-1 persistence. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Accessed April 1, 2025
20. Gunst JD, Pahus MH, Rosás-Umbert M, et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022;28(11):2424-2435. doi:10.1038/s41591-022-02023-7. Accessed April 1, 2025
21. University of Aarhus. Combining a TLR9 agonist with broadly neutralizing antibodies for reservoir reduction and immunological control of HIV infection: an investigator-initiated randomized, placebo-controlled, Phase IIa trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 7, 2019. NLM Identifier: NCT03837756. Accessed April 1, 2025
22. Gunst JD, Højen JF, Pahus MH, et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat Med. 2023;29(10):2547-2558. doi:10.1038/s41591-023-02547-6. Accessed April 1, 2025
23. Gunst JD, Reikvam DH, McMahon JH, et al. The impact of 3BNC117, 10-1074, and lefitolimod on HIV-1 persistence: the TITAN trial. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Abstract 136. Accessed April 1, 2025
24. Frontier Biotechnologies Inc. A Phase 2, multicenter, three-part study to establish the dosage, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 as long-acting maintenance therapy in virologically suppressed subjects with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2018. NLM Identifier: NCT03719664. Accessed April 1, 2025
25. Imperial College London. A randomised placebo controlled trial of ART plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo in treated primary HIV infection on viral control off ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2020. NLM Identifier: NCT04319367. Accessed April 1, 2025
26. Fidler S, Lee M, Collins S, et al. The RIO trial: a randomised placebo-controlled study of 2 LS-bNAbs (3BNC-117-LS & 10-1074-LS) in people treated in early HIV. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 9-12, 2025; San Francisco, CA. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2025. Accessed April 1, 2025
27. Frontier Biotechnologies Inc. The Phase 2, two arms, one site, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 in virologically suppressed subjects with HIV-1 infection after analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 22, 2021. NLM Identifier: NCT04819347. Accessed April 1, 2025
28. Frontier Biotechnologies Inc. A multicenter, two-arm, 24-week study of albuvirtide in combination with 3BNC117 in patients with multi-drug resistant (MDR) HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 17, 2020. NLM Identifier: NCT04560569. Accessed April 1, 2025
29. ANRS, Emerging Infectious Diseases. A randomised Phase II placebo-controlled trial of antiretroviral therapy (ART) plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo during primary HIV-1 infection to study the impact on post-treatment HIV control. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 3, 2022. NLM Identifier: NCT05300035. Accessed April 1, 2025
30. National Institute of Allergy and Infectious Diseases (NIAID). 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. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 5, 2023. NLM Identifier: NCT06071767. Accessed April 1, 2025
31. Gilead Sciences. A Phase 2 randomized, open-label study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with the capsid inhibitor lenacapavir as long-acting treatment dosed every 6 months in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 6, 2023. NLM Identifier: NCT05729568. Accessed April 1, 2025
32. Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections. A randomized, double-blind, placebo-controlled study of the combination of two long-acting broadly neutralizing antibodies at ART initiation in adults living with HIV-1 in Sub-Saharan Africa: the ACACIA Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 4, 2024. NLM Identifier: NCT06205602. Accessed April 1, 2025
33. Rockefeller University. An open label, randomized study of the safety and antiretroviral activity of 3BNC117 and 10-1074 in HIV-infected individuals on combination antiretroviral therapy and during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 3, 2018. NLM Identifier: NCT03526848. Accessed April 1, 2025
34. Rockefeller University. An open label, single arm study of the safety, pharmacokinetics and antiretroviral activity of the combination of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2020. NLM Identifier: NCT04250636. Accessed April 1, 2025
35. Luis Montaner. Pilot study on innate activation and viral control in HIV-infected adults undergoing an analytical treatment interruption after administration of pegylated interferon alpha 2b with broadly HIV-1 neutralizing antibodies (3BNC117, 10-1074). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 30, 2018. NLM Identifier: NCT03588715. Accessed April 1, 2025
36. Gilead Sciences. A Phase 1b randomized, blinded, proof-of-concept study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with capsid inhibitor lenacapavir (GS-6207) in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 19, 2021. NLM Identifier: NCT04811040. Accessed April 1, 2025
37. Rockefeller University. An open label, single arm study of the safety and antiretroviral activity of two long-acting broadly neutralizing antibodies plus an IL-15 superagonist in ART-treated adults living with HIV during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 8, 2022. NLM Identifier: NCT05245292. Accessed April 1, 2025
38. National Institute of Allergy and Infectious Diseases (NIAID). A randomized placebo-controlled study to evaluate the safety and effects of repeated doses of 3BNC117-LS and 10-1074-LS on persistent viral reservoirs in people living with HIV and on suppressive antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2022. NLM Identifier: NCT05612178. Accessed April 1, 2025
39. AIDS Clinical Trials Group. A Phase I, randomized, placebo-controlled study of the safety, antiviral & immunomodulatory activity of broadly neutralizing antibodies 3BNC117-LS-J and 10-1074-LS-J in combination in ART-treated adults in sub-Saharan Africa living with HIV during a monitored analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 14, 2023. NLM Identifier: NCT06031272. Accessed April 1, 2025

Last Reviewed: April 1, 2025