title: Passive transfer of neutralizing mAb KD-247 reduces plasma viral load in patients chronically infected with HIV-1.
abstract: OBJECTIVE
  Neutralizing antibodies against HIV-1 such as a humanized mAb KD-247 can mediate effector functions that attack infected cells in vitro. However, the clinical efficacy of neutralizing antibodies in infected individuals remains to be determined. We evaluated the safety, tolerability and pharmacokinetics of KD-247 infusion and its effect on plasma HIV-1 RNA load and CD4 T-cell count.
  
  
  METHODS
  KD-1002 is a phase Ib, double-blind, placebo-controlled, dose-escalation study of KD-247 in asymptomatic HIV-1 seropositive individuals who did not need antiretroviral therapy. Individuals were randomized to 4, 8 or 16 mg/kg KD-247 or placebo, and received three infusions over a 2-week period.
  
  
  RESULTS
  Patients were randomized to receive one of the three doses of KD-247 and the treatment was well tolerated. We observed a significant decrease in HIV RNA in the 8 and 16 mg/kg KD-247 cohorts, with two individuals who achieved more than 1 log reduction of HIV RNA. Two patients in the 16 mg/kg cohort had selections and/or mutations in the V3-tip region that suggested evasion of neutralization. Long-term suppression of viral load was observed in one patient despite a significant decrease in plasma concentration of KD-247, suggesting effects of the antibody other than neutralization or loss of fitness of the evading virus.
  
  
  CONCLUSIONS
  The results indicate that KD-247 reduces viral load in patients with chronic HIV-1 infection and further clinical trials are warranted.
authors: aCenter for AIDS Research, Kumamoto University, Kumamoto bAIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan cQuintiles Inc., Overland Park, Kansas, USA dThe Chemo-Sero-Therapeutic Research Institute (Kaketsuken), Kumamoto, Japan.
authors: Shuzo
authors: S
authors: Matsushita
authors: Kazuhisa
authors: K
authors: Yoshimura
authors: Kristel Paola
authors: KP
authors: Ramirez
authors: Jaya
authors: J
authors: Pisupati
authors: Toshio
authors: T
authors: Murakami
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000187:drug effects / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D012367:RNA, Viral; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D012367:RNA, Viral