Efficacy and Safety of Long Acting HIV Fusion Inhibitor Albuvirtide in Antiretroviral-Experienced Adults with HIV-1: Interim 48 Week Results from the Randomized, Controlled, Phase 3 Trial, Non-Inferiority TALENT Study

Abstract

Background: Albuvirtide is a once-weekly injectable HIV-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on WHO-recommended first-line treatment for > 6 months with a plasma viral load > 1000 copies per mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies per mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Findings: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies per mL (difference: 14.4%, 95% CI: -3.0 to 31.9), meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated (94.9% vs. 74.4%, difference: 20.5%, 95% CI: 5.7 to 35.2, p=0.01). The frequency of grade 3-4 adverse events was similar in the two groups (14.0% vs. 11.1%); the most common adverse events were diarrhea (8.6% vs. 14.1% for the ABT and NRTI groups, respectively), upper respiratory tract infections (4.3% vs. 6.1%), and grade 3-4 increases in triglyceride concentration (6.5% vs. 4.0%). Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received TDF than in those of the ABT group (mean change in eGFR: -11.47 vs. -1.22 mL/min/1.73m2, p=0.02). Interpretation: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis suggests that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Clinical Trial Number: This study is registered with ClinicalTrials.gov, number NCT02369965 and with the Chinese Clinical Trial Registry, number ChiCTR-TRC-14004276. Funding Statement: This work was supported by the Frontier Biotechnologies Inc., Ministry of Science and Technology of China (Grant No. 2013ZX09101001, 2017ZX09201007), the Beijing Municipal of Science and Technology Major Project (D141100000314005, D141100000314002, D161100000416003), the National Natural Science Foundation of China (81772165, 81571973), and Beijing Key Laboratory for HIV/AIDS Research (BZ0089). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: CY, RL, JH, and DX have received salary support from Frontier Biotechnologies Inc. All authors had full access to all study data and analyses, and approved the final report. All other authors have declared that no competing interests exist. Ethics Approval Statement: The institutional ethics committee at each site reviewed and approved the protocol and the written informed consent form which was provided according to the declaration of Helsinki. Each patient gave written informed consent before undergoing study procedures. The methods were carried out in accordance with approved guidelines and regulations.