teropavimab (GS-5423) / Rockefeller University, Gilead - LARVOL DELTA

IDUNN: bNAbs and Anti-PD-1 in HIV (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Ole Schmeltz Søgaard

New P2 trial • Human Immunodeficiency Virus • Infectious Disease • CD4

Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial. (PubMed, Nat Med) - P2 | "Sixty-eight adult men living with human immunodeficiency virus (HIV), who were predominantly white and initiated antiretroviral therapy (ART) during primary or early-stage infection, underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS (arm A, n = 34) or saline (arm B, n = 34). Finally, comparison of preinfusion and prerebound HIV-1 proviral reservoir showed a decrease in intact but not defective proviruses in arm A but not in arm B. Together, these findings suggest that baseline humoral immunity and prolonged exposure to LS-bNAbs jointly shape post-treatment viral rebound dynamics in individuals who initiate ART during primary infection. ClinicalTrials.gov identifier: NCT04319367 ."

Journal • P2 data • Fatigue • Human Immunodeficiency Virus • Infectious Disease • CD4

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1 (clinicaltrials.gov) - P1/2 | N=36 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Suspended

Trial suspension • Human Immunodeficiency Virus • Infectious Disease • CD4

ACACIA: Antiretrovirals Combined With Antibodies for HIV-1 Cure In Africa (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

PAUSE: Pausing Antiretroviral Treatment Under Structured Evaluation (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Enhanced HIV-1 control after antibody therapy is associated with autologous antibodies and reservoir clearance in the RIO trial (AIDS 2026) - "Participants were randomly assigned to receive one or two doses of the long-acting bNAbs 3BNC117-LS and 10-1074-LS (Arm A) or saline placebo (Arm B). Dual long-acting bNAb therapy administered during early HIV-1 acquisition significantly delays viral rebound following ART interruption and is associated with distinct patterns of post-treatment virological control, including fluctuating low-level viremia. These effects are accompanied by accelerated decay of intact proviral genomes and selective pressure on rebound viruses, providing mechanistic insight into antibody-mediated HIV remission and informing the development of future combination cure strategies."

Human Immunodeficiency Virus • Infectious Disease • CD4

HIV viral control after bNAb “wash-out” and relationship to HIV viraemia at dosing; preliminary results from the RIO trial (AIDS 2026) - " The RIO trial randomly allocated participants to stop ART (ATI-1) after receiving two LS-bNAbs (10-1074-LS and 3BNC-117-LS, 1-2 doses >20 weeks apart) (Arm A) or placebo (Arm B). Two LS-bNAbs are capable of maintaining viral control off ART for over a third of participants when below therapeutic levels irrespective of viraemia prior to LS-bNAb dosing."

Human Immunodeficiency Virus • Infectious Disease

Efficacy and safety of twice-yearly lenacapavir, teropavimab, and zinlirvimab as an HIV-1 treatment for up to 104 weeks (AIDS 2026) - P2 | "d Cardiac arrest unrelated to study treatment (methamphetamine/amphetamine intoxication). Twice-yearly LEN+TAB+ZAB maintained high rates of virologic suppression for up to 2 years and demonstrated a favorable safety profile."

Clinical • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • CD4

Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy (clinicaltrials.gov) - P3 | N=590 | Not yet recruiting | Sponsor: Gilead Sciences

New P3 trial • Human Immunodeficiency Virus • Infectious Disease

Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens (clinicaltrials.gov) - P3 | N=590 | Not yet recruiting | Sponsor: Gilead Sciences

New P3 trial • Human Immunodeficiency Virus • Infectious Disease

Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial. (PubMed, Lancet HIV) - P2 | "Long-acting bNAbs can sustain extended ART-free viral control in people treated during early-stage HIV and represent a promising step towards achieving ART-free HIV remission."

Journal • Fatigue • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease

A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P2 | N=83 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Dec 2029 ➔ Dec 2030

Trial completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803) (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Rockefeller University | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Dec 2025

Trial completion • Trial completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

PAUSE: Pausing Antiretroviral Treatment Under Structured Evaluation (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Trial primary completion date: Apr 2026 ➔ Oct 2025

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: week-26 primary outcome results from a multicentre, open-label, randomised, active-controlled, phase 2 study. (PubMed, Lancet Microbe) - P1, P2 | "A single administration of lenacapavir, teropavimab, and zinlirvimab in the study population demonstrated similar efficacy to daily oral ART through to week 26. This regimen was well tolerated, with no serious adverse events, supporting its potential as the first complete twice-yearly, long-acting, injectable HIV-1 treatment."

Journal • P2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

T cell immunity predicts clinical outcomes on stopping antiretroviral treatment after HIV-specific broadly neutralising antibody therapy. (PubMed, medRxiv) - "The RIO trial assessed HIV-specific cell-mediated immunity after dosing with two long-acting bNAbs (10-1074-LS and 3BNC117-LS) in people treated with antiretroviral therapy (ART) since early stage HIV followed by treatment interruption. Baseline ELISpot responses were associated with faster rebound. These data highlight the complex interplay between bNAbs and T cells, identify a post-bNAb protective T cell-driven vaccinal effect, and reinforce the role of immune-based interventions as part of HIV cure strategies."

Clinical data • Journal • Human Immunodeficiency Virus • Infectious Disease • CD8

Time to HIV rebound after antiretroviral therapy interruption: a double-blind randomised placebo-controlled trial of long-acting broadly neutralising antibodies; The RIO Trial. (PubMed, medRxiv) - P2 | "RIO is a 1:1 randomised double-blind placebo-controlled trial of two LS-bNAbs (3BNC117-LS & 10-1074-LS) in individuals virally suppressed on ART initiated since early-stage HIV. LS-bNAbs represent a major advance towards ART-free HIV control and remission as an achievable goal. These findings will inform future combination strategies to enhance the mechanisms of post-bNAb HIV control."

Journal • Human Immunodeficiency Virus • Infectious Disease

A 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 (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=79 ➔ 105

Enrollment change • Human Immunodeficiency Virus • Infectious Disease • CD4

A 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 (clinicaltrials.gov) - P1 | N=79 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | N=200 ➔ 79 | Trial completion date: Dec 2025 ➔ Mar 2027 | Trial primary completion date: Dec 2025 ➔ Mar 2027

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Association of HIV Envelope Susceptibility Signatures to Broadly Neutralizing Antibodies and Presence of p24 CTL Epitopes During Acute HIV-1 Infection. (PubMed, J Acquir Immune Defic Syndr) - "The findings contribute to our understanding of bNAb susceptibility and epitope prevalence during early stages of HIV-1 infection, informing future treatment and cure strategies."

Journal • Human Immunodeficiency Virus • Infectious Disease

3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803) (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Rockefeller University | Trial completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial. (PubMed, medRxiv) - "RIO is an ongoing double blind randomized placebo controlled human trial in which participants that started antiretroviral therapy (ART) during primary or early-stage infection underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long acting broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS (Arm A), or saline (Arm B). Notably, there was a significant correlation between initial reservoir sensitivity to autologous antibodies and to 10-1074 and time to rebound. Finally, comparison of pre-infusion and pre-rebound HIV-1 proviral reservoir in participants that received antibodies showed that the reservoir of intact proviruses decayed faster than earlier reports with a half-life of 0.65 years."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Resistance Analysis of Low-Level Virologic Rebound During HIV-1 Treatment with Lenacapavir and Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab. (PubMed, J Infect Dis) - P1 | "Lenacapavir, teropavimab, and zinlirvimab maintained a high rate of virologic suppression through W26, with a low rate of emergent lenacapavir resistance and no bNAb resistance, supporting further evaluation of this combination in Phase 2."

Journal • Human Immunodeficiency Virus • Infectious Disease