CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

safety of ABT+3BNC117 combined with an optimized background regimen (OBR) in adults with multidrug-resistant (MDR) HIV-1. Methods: In this ongoing phase 2 trial in two countries, we enrolled patients with MDR HIV-1 infection who had failed multiple antiretroviral therapies. All participants had a viral load over 1000 copies of HIV-1 RNA per mL. After a control period (day 0 to day 6) during which participants continued their current therapy, ABT+3BNC117 was infused on days 7, 8, and 9, and the viral load was then measured at week 2 (treatment period). On day 14, all eligible participants were randomly assigned in a 1:1 ratio to Group A (receiving ABT weekly and 3BNC117 biweekly) or Group B (receiving both ABT and 3BNC117 biweekly), combined with an OBR that included at least one fully active agent for the same 24-week maintenance period. The primary endpoint was the proportion of participants who experienced a reduction in viral load of at least 0.5 log 10 RNA copies/mL between day 7 and day 14. Results: A total of 16 participants completed the study. The mean baseline viral load was 4.45 log 10 RNA copies/mL. Of the 16 participants in the intention-to treat population, 10 (62.5%) had a decrease in viral load of at least 0.5 log 10 RNA copies/mL from baseline ( p <0.001 for the comparison with the control period). At the end of treatment (EOT), participants who had received ABT+3BNC117 plus OBR had a mean decrease in viral load of 2.52 log 10 RNA copies/mL from baseline, with 87.5% achieving levels below 50 RNA copies/mL. At week 26, 75% of Group A and 100% of Group B had a viral load below 50 RNA copies/mL. 2 participants had virologic failure. No participants died from causes related to underlying illnesses and no serious adverse events related to ABT+3BNC117 were identified. In the eight-week analysis after ABT+3BNC117 cessation in 14 participants, 92.8% had a viral load below 50 RNA copies/mL. Conclusions: In patients with MDR HIV-1 infection who have advanced disease and limited treatment therapeutic options, the combination of ABT+3BNC117 had significant antiviral activity during a 34-week study period.

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A 24-Week Phase II Maintenance Study of TMB-365/TMB-380 Q8W in People With Suppressed HIV-1 Infection YingAn Lai 1 , Edwin DeJesus 2 , Michael Sension 3 , Gordon E. Crofoot 4 , Moti Ramgopal 5 , Mezgebe Berhe 6 , Kuei-Ling Kuo 1 , Jacob P. Lalezari 7 , Chin-Ming Chang PhD 1 , Martin H. Markowitz 1 1 TaiMed Biologics Inc, Taipei City, Taiwan, 2 Orlando Immunology Center, Orlando, FL, USA, 3 CAN Community Health, Fort Lauderdale, FL, USA, 4 The Crofoot Research Center, Houston, TX, USA, 5 Midway Immunology and Research Center, Fort Pierce, FL, USA, 6 North Texas Infectious Diseases Consultants, Dallas, TX, USA, 7 Quest Clinical Research, San Francisco, CA, USA Background: TMB-365, a second-generation post-attachment bNAb binds to the second domain of CD4 and displays improved PK, antiviral activity, and breadth of coverage when compared to ibalizumab. TMB-380 (VRC07-523LS) is a bNAb that binds to the CD4 binding site of HIV Env and has potent antiviral activity and favorable safety and PK profile. Here we present results of a 24-week phase 2 maintenance study of the combination with complementary MOA in people with suppressed HIV-1 infection (NCT05275998). Methods: Participants suppressed (VL<50 c/mL) with continuous oral cART for at least 6 months, clinically stable, and had no history of virologic failure (VF) were enrolled (target N=20). After screening, oral cART was discontinued and 4800 mg of TMB-365 and TMB-380 were infused every 8 weeks for 3 doses (baseline, week 8, week 16). Oral cART was restarted at the week 24 visit. All infusions were performed over 60 minutes in outpatient clinics with vital sign determinations every 15 minutes during and up to 60 minutes post-infusion. VF was defined as 2 consecutive HIV-RNA values >50 c/mL at least 2 weeks apart. Efficacy was evaluated as % participants with VL<50 c/mL at week 24. Results: 21 individuals were enrolled; 1 developed a GI bleed (before dosing, unrelated) between screening and day 1 and was replaced. 18 of 20 completed the study. Age range was 24 to 67 years; 1/21 were female; 10/21 were White (non-Hispanic); and median CD4 count was 706 cells/µL. Two participants did not complete the study. One participant developed a generalized rash 32 days after the first infusion and participation was terminated. One participant developed an atypical papular eruption 7 days after infusion #1 and withdrew. No SAEs, Grade 3 or 4 adverse events or acute infusion reactions were observed. Treatment-emergent AEs (N=48) were mild to moderate. 16 were attributed to infusions with bNAbs; rash (4), fatigue (4), headache (3), flushing (2), fever (1), chills (1), aches (1). No cases of protocol-defined VF were observed. At week 24, 16/17 (94%) with plasma VL below 50 c/mL, one had VL of 59 c/mL, N=2 early D/C, N=1 no data. The preliminary mean TMB-365 and TMB-380 concentrations at week 24 are 29 and 107 μg/mL, respectively. Conclusions: Every 8-week infusions of TMB-365 and TMB-380 with complementary MOA at 4800 mg each are safe and effective as a complete maintenance therapy in people with suppressed HIV-1 infection. No confirmed VF was observed. Results support the development of TMB-365/TMB-380 into phase 2b. A Multicenter Study of Albuvirtide Combined With 3BNC117 in Multidrug-Resistant HIV-1 Infection Yihong Zhou, Yaokai Chen, Vijay Harypursat, Yuanyuan Qin Chongqing Public Health Medical Center, Chongqing, China Background: For some individuals with HIV-1 infection who have failed multiple antiretroviral regimens and have limited treatment options, there is an urgent need for new antiretroviral drugs with novel mechanisms of action. Albuvirtide (ABT) is an HIV-1 fusion inhibitor and 3BNC117 is an HIV-specific, broadly neutralizing monoclonal antibody. We aimed to assess the efficacy and

Poster Abstracts

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