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Investigational Antiviral Drugs
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
John Mills, Suzanne M. Crowe, Marianne Martinello
BMS-955176 is a second-generation HIV maturation inhibitor that inhibits the last protease cleavage event between capsid protein p24 and spacer peptide SP1 in Gag, binding irreversibly to Gag and resulting in the release of immature, noninfectious particles. It is active against a panel of RT-, integrase- and protease-resistant HIV strains. In a phase IIa dose-ranging study, 60 HIV-1 infected subjects with HIV-1 RNA ≥ 5000 copies/ml and CD4 counts of ≥ 200 cells/μl received an oral suspension of BMS-955176 in doses ranging from 5 to 120 mg/day or placebo once daily for 10 days. The median VL response daily decreased to a plateau at approximately −1.64 log10 copies/ml at doses of 40–120 mg daily, regardless of baseline Gag polymorphisms (positions evaluated: V362, Q369, V370, and T371). BMS-955176 was generally well tolerated at all doses. A study of BMS-955176 (80 mg/day) plus atazanavir (400 mg/day) or BMS-955176 (40 mg/day) plus atazanavir–ritonavir (300/100 mg/day) demonstrated a median decline in HIV viral load of 2.2 log10 copies/ml, similar to that achieved with the standard of care control (tenofovir–emtricitabine plus atazanavir–ritonavir) over a 28-day treatment period. Three phase IIb studies are under way, including an efficacy study (NCT02386098) (Hwang et al., 2015; Nowicka-Sans et al., 2012).
Current insights into anti-HIV drug discovery and development: a review of recent patent literature (2014–2017)
Published in Expert Opinion on Therapeutic Patents, 2018
Xiaofang Zuo, Zhipeng Huo, Dongwei Kang, Gaochan Wu, Zhongxia Zhou, Xinyong Liu, Peng Zhan
Triterpene derivative bevirimat (49) was an HIV-1 maturation inhibitor that reached phase II clinical trials before being discontinued [103]. BMS-955176 (50) is a potent, orally active, new generation HIV-1 maturation inhibitor, which is currently in phase IIb clinical trials as part of a combination antiretroviral regimen [104,105].