title: Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial.
abstract: Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds directly to HIV-1 gp120, blocking initial viral attachment and entry into host CD4+T-cells. Efficacy, safety and dose-response data of fostemsavir in treatment-experienced, HIV-1-infected subjects, through week 48, are reported.
  
  
  
  AI438011 is an ongoing Phase IIb, randomized, active-controlled trial (NCT01384734). Subjects were randomized 1:1:1:1:1 into five arms: fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily or 1,200 mg once daily) and a reference arm (ritonavir-boosted atazanavir [ATV/r] 300/100 mg once daily), each with a backbone of raltegravir 400 mg twice daily plus tenofovir disoproxil fumarate 300 mg once daily.
  
  
  
  In total, 251 subjects were treated. Through week 48, the proportion of fostemsavir subjects with HIV-1 RNA <50 copies/ml was 61-82% and 77-95% (modified intent-to-treat [mITT] and observed analysis, respectively); 71% and 88% for ATV/r subjects (mITT and observed). Observed virological response rates were 74-100% versus 96% (fostemsavir versus ATV/r) in subjects with baseline viral load <100,000 copies/ml and 60-91% versus 71% when baseline viral load was ≥100,000 copies/ml. Across fostemsavir arms, median CD4+T-cell count increases from baseline were 145-186 cells/µl and 142 cells/µl for the ATV/r arm. Fostemsavir doses were generally well tolerated and no fostemsavir-related adverse events led to discontinuation.
  
  
  
  Through week 48, fostemsavir continued to be well tolerated and showed similar efficacy to ATV/r. These results support the ongoing Phase III trial in heavily treatment-experienced adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining). ClinicalTrials.gov identifier: NCT01384734.
authors.affiliation: AIDS Research Consortium of Atlanta, Atlanta, GA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Quest Clinical Research, San Francisco, CA, USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Lalezari
authors.affiliation: Desmond Tutu HIV Foundation, Cape Town, South Africa.
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
authors.affiliation: Asociacion Civil Via Libre, Lima, Peru.
authors.forename: Yvett
authors.initials: Y
authors.lastname: Pinedo
authors.affiliation: Asistencia Cientifica de Alta Complejidad SAS, Bogotá, Columbia.
authors.forename: Otto A Sussmann
authors.initials: OAS
authors.lastname: Pena
authors.affiliation: Fundacion Huesped, Buenos Aires, Argentina.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Stock
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT, USA.
authors.forename: Samit R
authors.initials: SR
authors.lastname: Joshi
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Hanna
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Lataillade
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D011355:Prodrugs; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011355:Prodrugs