title: Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 x 10(6)/L CD4 cell counts: A randomized controlled trial.
abstract: BACKGROUND
  Despite enormous improvements achieved through the use of antiretroviral therapies (ARTs), the risk for eventual human immunodeficiency virus (HIV) disease progression remains high. Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression.
  
  
  OBJECTIVE
  To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs.
  
  
  METHODS
  Multicenter, double-blind, placebo-controlled, randomized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV.
  
  
  METHODS
  Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART (or no therapy) were screened and 2527 were randomized.
  
  
  METHODS
  Ten units of HIV-1 Immunogen, derived from a Zairian HIV isolate, inactivated and formulated with incomplete Freund adjuvant, was administered intramuscularly every 12 weeks. The placebo was incomplete Freund adjuvant. Changes in ARTs were allowed.
  
  
  METHODS
  HIV progression-free survival; secondary end points included overall survival, changes in HIV RNA, CD4 cell counts, CD4 percentage, body weight, and immunogenicity.
  
  
  RESULTS
  The overall event rate was 1.8 per 100 person-years of follow-up. Fifty-three subjects developed clinical progression in each treatment group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.66-1.42; P =.89). There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups, respectively (RR, 0.81; 95% CI, 0.44-1. 48; P =.49). There were no statistically significant differences between the groups with respect to changes in HIV RNA (P =.59), CD4 percentage (P =.63), or body weight (P =.89). Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group (P =.02).
  
  
  CONCLUSIONS
  HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.
authors.affiliation: San Francisco General Hospital, 995 Potrero Ave, San Francisco, CA 94110, USA. jkahn@php.ucsf.edu
authors.forename: J O
authors.initials: JO
authors.lastname: Kahn
authors.forename: D W
authors.initials: DW
authors.lastname: Cherng
authors.forename: K
authors.initials: K
authors.lastname: Mayer
authors.forename: H
authors.initials: H
authors.lastname: Murray
authors.forename: S
authors.initials: S
authors.lastname: Lagakos
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; C098825:HIV-1 immunogen, incomplete Freund's adjuvant