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Efficacy and safety of long acting HIV fusion inhibitor albuvirtide in treatment-experienced HIV-1 infected patients: week 48 analysis from the randomized controlled phase 3 TALENT study

Title
Efficacy and safety of long acting HIV fusion inhibitor albuvirtide in treatment-experienced HIV-1 infected patients: week 48 analysis from the randomized controlled phase 3 TALENT study
Presenter
Lili Dai
Authors
H. Wu (1), C. Yao (2), T. Zhang (3), Q. Zhao (4), W. Cai (5), M. Wang (6), H. Lu (7), H. Wang (8), Y. Zheng (9), B. Zhu (10), J. Yu (11), Y. Sun (12), M. Zhao (13), W. Lun (14), W. Xia (1), L. Sun (1), L. Dai * (1), T. Jiang (1), Q. Zheng (15), H. Peng (16), Y. Wang (16), R. Lu (2), J. Hu (2), M. Wang (1), F. Zhang (14), D. Xie (2), TALENT Study Team
Institutions
(1) Beijing You'an Hospital, Capital Medical University, Beijing, China, (2) Frontier Biotechnologies Inc., Nanjing, China, (3) Beijing You'an Hospital, Capital Medical University, Henan, China, (4) Infectious Disease Hospital of Henan Province, Henan, China, (5) The Eighth People''s Hospital of Guangzhou, Guangzhou, China, (6) The First Hospital of Changsha, Changsha, China, (7) Shanghai Public Health Clinical Center, Shanghai, China, (8) The Third People''s Hospital of Shenzhen, Shenzhen, China, (9) The Second Xiangya Hospital of Central South University, Xiangya, China, (10) The First Affiliated Hospital, Zhejiang University, Zhejiang, China, (11) Xixi Hospital of Hangzhou, Hangzhou, China, (12) Tangdu Hospital of the Fourth Military Medical University, Tangdu, China, (13) 302 Military Hospital of China, Beijing, China, (14) Beijing Ditan Hospital, Capital Medical University, Beijing, China, (15) Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China, (16) Beijing Co-CRO Medical Development Co., Ltd., Beijing, China

BACKGROUND: Albuvirtide, a peptide-based and long-acting fusion inhibitor, blocks the HIV-1 Env-mediated cell membrane fusion and virus entry. We present the 48-week analysis of the TALENT study (ClinicalTrials.gov, NCT02369965), that assessed the safety and efficacy of albuvirtide plus lopinavir-ritonavir in antiretroviral-experienced adults with HIV-1.
METHODS: TALENT is a phase 3, randomized, controlled, open-label, multicenter non-inferiority study. Eligible subjects failed the WHO first-line ART therapy with plasma viral load > 1000 copies per mL were randomly assigned (1:1) to receive 320 mg albuvirtide (once weekly) plus ritonavir-boosted lopinavir (albuvirtide group) or 2 NRTIs plus ritonavir-boosted lopinavir (2 NRTIs group). The primary endpoint was the proportion of patients with plasma viral load less than 50 copies per mL at 48 weeks by FDA snapshot algorithm. Non-inferiority was pre-specified with a margin of 12%. A modified intention-to-treat analysis was carried out.
RESULTS: A total of 1291 patients were screened and 418 were enrolled. Safety analysis included 401 patients (195 albuvirtide vs. 206 2NRTIs) who received at least one dose of the study drugs. 383 patients (185 albuvirtide vs. 198 2NRTIs) were allocated for the modified intent-to-treat analysis, excluding 18 patients (10 albuvirtide vs. 8 2NRTIs) either for severe protocol violations or without any viral load data. At 48 weeks, 75.7% patients in the albuvirtide group had HIV-1 RNA less than 50 copies per mL versus 77.3% in the 2NRTIs group (difference -1.6%, 95% CI '10.1 to 6.9), meeting the non-inferiority criteria. All patients had good drug adherence of over 90% in both groups. No injection site reactions were observed in albuvirtide group during the 48-week treatment duration. One patient in 2 NRTIs group died during the study, but not related to drugs. Patients in albuvirtide group had no drug-related serious adverse events compared with 2 patients in 2 NRTIs group. Adverse events leading to discontinuation were 2 (1.0%) in both groups. The overall frequencies of drug-related adverse events were similar in both groups, commonly included diarrhea, nausea and triglycerides elevation.
CONCLUSIONS: Two-drug regimen of albuvirtide in combination with lopinavir/ritonavir was well tolerated and non-inferior to the standard second-line three-drug regimen at 48 weeks.