Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study

Abstract

Background Albuvirtide is a once-weekly injectable human immunodeficiency virus (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 the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results 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% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates 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. Trial registration ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov . Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx

Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus

“…However, the previous studies were primarily based on the bioinformatics approaches and lacked experimental evidence. After the SARS-CoV-2 outbreak, we actually tested a panel of HIV-1 fusion inhibitors, including T20, the recently approved long-lasting albuvirtide (ABT) [ 26 ], T1249, T2635 [ 27 ], sifuvirtide (SFT) [ 28 ], and 2P23 that mainly targets the gp41 pocket site [ 29 ]. While they potently inhibited HIV-1, none was found to have inhibitory activity against SARS-CoV-2 at a concentration as high as 25 or 50 μM (Table S1).…”

Tolerability and Adherence of Antiretroviral Regimens Containing Long-Acting Fusion Inhibitor Albuvirtide for HIV Post-Exposure Prophylaxis: A Cohort Study in China

“…The efficacy and safety of an ABT-containing 2-drug combination (ABT ? LPV/r) have been demonstrated in randomized clinical trials and post marketing studies [20][21][22][23]. With the advantages of long-acting, minimal drug-drug interactions, a high barrier to resistance and early blockade of cell fusion mechanism, ABTcontaining 2-drug combinations are being considered as a promising HIV PEP option, especially in regions where STRs are not widely available.…”

“…The binding of ABT with serum albumin to form a conjugate is responsible for its extended half-life of 12 days [ 17 , 18 ], and it reduces the need for frequent intravenous administration [ 19 ]. The phase 3 TALENT study indicated that the dual regimen of ABT (weekly infusion) and oral daily ritonavir-boosted lopinavir (LPV/r) was well tolerated and non-inferior to the WHO-recommended second-line three-drug regimen in HIV patients with first-line treatment failure [ 20 ]. ABT was approved by the China National Medical Products Administration (NMPA) for marketing in 2018.…”

HIV-1 Entry and Membrane Fusion Inhibitors

“…Similar peptide fusion inhibitors, such as T1144 and Sifuvirtide, suffer similar disadvantages [ 115 , 116 ]. Another HR-2 peptide-derived inhibitor, Albuvirtide, also known as FB006M, has received marketing approval in China for the treatment of HIV-1 infection [ 117 ]. Conjugation of maleimidopropionic acid to the HR-2 peptide allows its binding to human serum albumin, effectively preventing protease degradation in vivo and leading to a half-life that is ~10-fold longer than that of Enfuvirtide [ 118 ].…”