A Phase I/II Study to Evaluate the Safety and Immunogenicity of ALVAC HIV Vaccines Alone and With AIDSVAX B/B in Children Born to HIV-Infected Mothers

Transmission of HIV from an untreated infected mother to her offspring is thought to occur to some infants perinatally and others at parturition. It is possible that administration of an immunogenic vaccine can reduce the vertical transmission of HIV-1 or moderate its course in infected infants. Successful early sensitization to HIV epitopes might succeed in preventing HIV infection. Alternately, the enhancement of HIV-specific immune function might also succeed in modifying HIV replication and affecting disease progression.

Sixty infants are treated in this randomized, double-blind study; 45 infants receive recombinant Canarypox virus, ALVAC-HIV vCP205, and 15 receive placebo. Mothers serve as proxy for their infants. All infants receive a minimum of four immunizations, at Weeks 0 (within 72 hours of birth), 4, 8, and 12. Initially, 24 patients are randomized to receive one of two doses of vCP205 or a saline placebo. When a suitable subunit vaccine is available, the protocol will be amended and 36 additional infants will be randomized to receive vCP205 alone or with a subunit vaccine at Weeks 4 and 8 (or vaccine placebo with or without subunit placebo). [AS PER AMENDMENT 11/5/97: 18 infants receive ALVAC-HIV vCP205 at one of two doses and 6 receive placebo.] [AS PER AMENDMENT 9/9/99: Cohort 1 received vCP205. Cohort 2 received a higher dose of vCP205. Cohort A received vCP205 placebo (saline). Cohorts 1, 2, and A were double-blinded and closed to accrual in March 1999. As of September 1999, infants are randomized to one of four new cohorts. Cohort 3 receives vCP1452 at Weeks 0, 4, 8, and 12. Cohort 4 receives vCP1452 at Weeks 0 and 4, then receives vCP1452 plus AIDSVAX B/E gp120 at Weeks 8 and 12. Cohort B receives vCP1452 placebo at Weeks 0, 4, 8, and 12. Cohort C receives vCP1452 placebo at Weeks 0 and 4, then receives vCP1452 placebo plus AIDSVAX B/E placebo at Weeks 8 and 12. All infants are followed every 2 weeks for the first 14 weeks of life, and then every 6 months until age 2. Cord blood is used to establish autologous B cell lines, and CTL assays are performed to characterize the immune response to HIV. In addition, CD4 count, viral load, and mucosal antibody responses are measured. Immunized infants who are not infected with HIV serve as controls for the immunogenicity of the vaccines in the infected infants.] [AS PER AMENDMENT 1/24/00: AIDSVAX B/E has been replaced with AIDSVAX B/B.]