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

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

Efficacy and Safety of a Twice-Yearly Regimen of Lenacapavir, Teropavimab, and Zinlirvimab: Phase 2 Week 52 Results (EACS 2025) - No abstract available

Clinical • P2 data • 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

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) | Trial completion date: Apr 2026 ➔ Aug 2029 | Trial primary completion date: Apr 2026 ➔ Apr 2028

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

Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Gilead Sciences | Phase classification: P1b ➔ P1

Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4

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

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

PAUSE: Pausing Antiretroviral Treatment Under Structured Evaluation (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Trial primary completion date: Jun 2025 ➔ Apr 2026

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

ACACIA: Antiretrovirals Combined with Antibodies for HIV-1 Cure in Africa (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Initiation date: Oct 2024 ➔ Jan 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Efficacy and safety analysis of lenacapavir with broadly neutralising antibodies, teropavimab and zinlirvimab, in people with HIV-1 highly sensitive to one or both broadly neutralising antibodies (HIV-Glasgow 2024) - P1b | "Conclusions : All participants who received LEN, TAB and high-dose ZAB maintained viral suppression with no difference in safety or tolerability between dose groups. These early phase results suggest that high treatment efficacy for the long-acting regimen of LEN, TAB and high-dose ZAB can be achieved when at least one antibody is highly active in people with HIV highly susceptible to one or both bNAbs."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4