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

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

Genotypic susceptibility to broadly neutralizing antibodies and fostemsavir of transmitted viruses, and evolution over time in the French acute HIV infection PRIMO cohort (EACS 2025) - "Method : We analyzed 191 sequences from participants in the acute infection French ANRS PRIMO cohort, over 3 decades (1988–2022), using sequence-based algorithms to predict susceptibility to teropavimab (3BNC117), zinlirvimab (10-1074) and entry inhibitors (fostemsavir, maraviroc). Conclusions : These findings underscore the importance of continuous surveillance of transmitted viruses to therapies targeting HIV-1 Env. Integrating phenotypic assessment with genotypic surveillance to refine resistance prediction models will also be important for predicting susceptibility, as well as the correlation with clinical efficacy in ongoing trials."

Human Immunodeficiency Virus • Infectious Disease • CD4

Efficacy and Safety of a Twice-Yearly Regimen of Lenacapavir, Teropavimab, and Zinlirvimab: Phase 2 Week 52 Results (EACS 2025) - P1, P2 | "Conclusions : In this first multiple-dose analysis, twice-yearly LEN+TAB+ZAB maintained viral suppression and was well tolerated. LEN+TAB+ZAB has the potential to be the first complete twice-yearly treatment regimen for PWH with susceptible viruses."

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

Qualitative Insights into the Lived Experiences of People living with HIV who Participated in an Analytical Treatment Interruption in the RIO Randomised-Controlled Trial (EACS 2025) - "Method : RIO is a phase 2 double-blinded randomised placebo-controlled trial of HIV-specific broadly neutralising antibodies (3BNC117-LS and 10-1074-LS) in people living with HIV. Preparation for viral rebound, its impact on relationships and ART adherence on reinitiation of therapy maybe important discussions when planning future ATI trials. Researchers should optimise psychosocial safety and remain vigilant to provide support during these key moments."

Clinical • Human Immunodeficiency Virus • Infectious Disease

AbVax: Combination Vaccination and Broadly Neutralising Antibody Therapy in HIV (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Teropavimab and zinlirvimab sensitivity in people living with multidrug-resistant HIV-1: data from the PRESTIGIO Registry. (PubMed, Microbiol Spectr) - P | "The findings indicate that a significant proportion of the population remains susceptible to these novel treatments, irrespective of their viral suppression status. These results offer a promising basis for developing new therapeutic strategies to improve outcomes for individuals with multidrug-resistant HIV who have a history of extensive treatment, paving the way for future clinical trials aimed at achieving long-term viral suppression with novel drug regimens."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Phase 2 Pharmacokinetics and Anti-Drug Antibody Results of the Investigational Twice-Yearly HIV-1 Treatment Regimen Lenacapavir, Teropavimab, and Zinlirvimab (IDWeek 2025) - No abstract available

P2 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Pooled safety and tolerability of twice-yearly lenacapavir with teropavimab and zinlirvimab for HIV-1 treatment (IDWeek 2025) - No abstract available

Clinical • Human Immunodeficiency Virus • Infectious Disease

Pooled safety and tolerability of twice-yearly lenacapavir with teropavimab and zinlirvimab for HIV-1 treatment (IDWeek 2025) - No abstract available

Clinical • Human Immunodeficiency Virus • Infectious Disease

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 | Recruiting ➔ Active, not recruiting | N=48 ➔ 32

Enrollment change • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

HIV-specific T-cell responses in suppressed people with HIV-1 receiving lenacapavir, teropavimab, and zinlirvimab (IAS-HIV 2025) - P1 | "Small increases in these responses were observed when the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074 were dosed during analytical treatment interruption or at ART initiation. Lack of increase from baseline in HIV-specific T-cell response following LEN+TAB+ZAB treatment in VS PWH suggests virologic suppression by LEN+TAB+ZAB did not increase viral antigen expression, which may have limited expansion of HIV-specific T-cells. This has implications for HIV-1 cure studies if greater antigen exposure if required for increased HIV-specific T-cell responses after bNAb administration."

Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Satisfaction, preference, and health-related quality of life changes using HIV-specific patient-reported outcome measures with a novel, twice-yearly administered HIV-1 treatment regimen (IAS-HIV 2025) - P2 | "BACKGROUND: The combination of lenacapavir (LEN), an approved HIV-1 capsid inhibitor, and two investigational broadly neutralizing antibodies (bNAbs), teropavimab (TAB) and zinlirvimab (ZAB), administered every 6 months (Q6M), is being evaluated in a Phase 2 open-label study (NCT05729568); we describe Week 26 (W26) patient-reported outcomes. Virologically suppressed (HIV-1 RNA <50 copies/mL) adults with HIV-1 highly susceptible to both bNAbs receiving oral antiretroviral therapy (ART) for =12 months were enrolled (N=83) and randomized 2:1 to subcutaneous LEN 927 mg (with LEN oral loading) plus intravenous TAB 2550 mg and ZAB 2550 mg Q6M, or to continue baseline oral ART. Participants switching to LEN, TAB, and ZAB Q6M reported improved treatment satisfaction and QoL by W26, with a moderate-to-strong preference for LEN, TAB, and ZAB over oral ART."

Clinical • HEOR • Patient reported outcomes • Human Immunodeficiency Virus • Infectious Disease

Altered viral rebound dynamics in chronically treated people with HIV given long-acting broadly neutralizing antibodies and N-803 (IAS-HIV 2025) - "We report preliminary results of the antiviral activity of the combination of two long-acting bNAbs and N-803 in people with HIV (PWH) during ATI. This open-label, single arm study enrolled chronically-treated PWH to receive single infusions of 3BNC117-LS (30 mg/kg) and 10-1074-LS (10mg/kg) followed by up to 8 subcutaneous injections of N-803 (6 mcg/kg) 3 weeks apart. In this ongoing study, we found that 15 of 25 chronically-treated PWH receiving a combination of bNAbs and N-803 controlled viremia for at least 6 months. Of these, 53% experienced prolonged low levels of or no viral rebound."

Human Immunodeficiency Virus • Infectious Disease • IL15

Safety and pharmacokinetic profile of a combination of two HIV broadly neutralizing antibodies, 3BNC117-LS-J and 10-1074-LS-J, in healthy American and African adults (IAS-HIV 2025) - "Both 3BNC117-LS-J and 10-1074-LS-J have demonstrated an acceptable safety profile and there were no significant differences between administered dose levels, combinations and administration routes. Region of study participants (US vs Africa) was a major factor influencing the PK profile."

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

AbVax: Combination Vaccination and Broadly Neutralising Antibody Therapy in HIV (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: University of Oxford

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

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=45 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Suspended ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults (clinicaltrials.gov) - P1/2 | N=225 | Completed | Sponsor: International AIDS Vaccine Initiative | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

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=45 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Suspended

Trial suspension • Human Immunodeficiency Virus • Infectious Disease • CD4

Lenacapavir Plus Two Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, for People With HIV-1 Highly Susceptible to Either Teropavimab or Zinlirvimab. (PubMed, J Infect Dis) - P1 | "More inclusive bNAb susceptibility criteria may be appropriate for future studies of this combination treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease

HIV-1 Reservoir Decay During Broadly Neutralizing Antibody Therapy in the RIO Trial (CROI 2025) - "RIO enabled examination of reservoir dynamics in 32 individuals receiving 3BNC117-LS and 10-1074-LS during ATI or after ART restart. When all measurements for both arms are considered jointly (n=32) the half-life of intact and defective reservoirs were 33 and 424 weeks respectively. Conclusions Antibody therapy in the RIO trial was associated with an average intact reservoir half-life decay which is 7-8 fold faster than prior reports."

Human Immunodeficiency Virus • Infectious Disease • CD4

Sustained Post-Rebound HIV Remission With Enhanced T-Cell Immunity After LS-bNAbs: A Case Report (CROI 2025) - "He then received one dose of dual bNAbs (10-1074LS; 3BNC117LS) and ART for 6 months. We will report analyses of integration sites, serology and viral outgrowth. Conclusions This is the first reported example of remission following a period of rebound after bNAb dosing and non-therapeutic bNAb levels, consistent with the vaccinal effect seen in NHP studies."

Case report • Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • GZMB • IL2 • TNFA

RIO: A Randomised Placebo-Controlled Study of 2 LS-bNAbs in People Treated in Early HIV (CROI 2025) - "Virally-suppressed participants (aged 18-60) who started ART during early HIV received up to two intravenous infusions >20 weeks apart of bNAbs (3BNC117-LS & 10-1074-LS) (Arm A) or placebo (Arm B), and undertook analytical treatment interruption (ATI). Conclusions Two LS-bNAbs were safe and significantly improved viral control off ART compared to placebo. Sustained viral suppression after bNAb dosing associated with enhanced T cell immunity is consistent with an immunologically-driven post-bNAb effect."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Transcriptional Analysis of Intestinal Immune Cells in People With HIV Receiving bNAbs (CROI 2025) - "Conclusions In this pilot study, we identified transcriptional changes in GALT-resident immune cells of individuals with well-controlled HIV infection on ART following the infusion of 3BNC117-LS and 10-1074-LS bNAbs. These changes suggest that bNAb exposure may modulate TNF/NF-kB and IFN signalling in CD4+ and CD8+ T cells – pathways that have been linked to immune cell susceptibility to HIV infection, innate and adaptive immune response to HIV and reactivation of latent infection."

Immune cell • IO biomarker • Human Immunodeficiency Virus • Infectious Disease • Oncology • CD8 • CTLA4 • FOXP3 • IFNG • IL2RA • NFKBIA • STAT1 • TNFA • TNFAIP3 • ZAP70

Efficacy and Safety of Lenacapavir, Teropavimab, and Zinlirvimab: Phase II Week 26 Primary Outcome (CROI 2025) - P1, P2 | "LTZ was well tolerated. These results demonstrate high efficacy of LTZ through W26 and support further investigation of LTZ as the first Q6M combination treatment for PWH."

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