AEGiS-11IAC: Safety, immunity, and risk behavior in HIV-1-uninfected volunteers representing diverse risk populations following recombinant envelope vaccinations: a three-year followup.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Safety, immunity, and risk behavior in HIV-1-uninfected volunteers representing diverse risk populations following recombinant envelope vaccinations: a three-year followup.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. Mo.A.284)
McElrath MJ, Montefiori D, Wolff M, Clements M, Gorse G, Keefer M, Graham B, Duliege AM, Francis D, Matthews T, Fast P, Corey L; Univ of Washington, Seattle WA, USA. Fax: 1-206-621-4178. E-mail: kd@u.washington.edu.

OBJECTIVES: Through the conduct of a phase II multicenter placebo-controlled double-blind vaccine trial in HIV(-) volunteers with either high or low HIV-1 risk behavior, to compare the clinical and immune responses, to determine the kinetics of HIV-1 neutralizing Ab responses after 4 immunizations, and to evaluate risk behavior in volunteer groups who represent potential target populations for efficacy trials.

METHODS: 296 volunteers were stratified into 1 of 6 risk groups: A) age 16-28 high risk heterosexuals (n=21), B) high risk gay/bisexual men (n=60), C) low risk gay/bisexual men (n=60), D) injection drug users (N-60), E) heterosexual partners of HIV+ (N=35), and F) low risk women and heterosexual men (n=60). Subjects were randomized into 1 of 4 treatment groups: 50 ug rgp120 SF-2 in MF 59 (Biocine) (n=129), 600 ug rgp120 MN in alum (Genentech) (n=128), MF59 alone (n=20), and alum alone (n=19). Immunizations were administered at 0, 1, 6 and 12 or 18 months. Safety evaluations were performed within 24-48 hr and day 14 after immunization. HIV-1 neutralizing Ab activity was tested by vital dye and multiple HIV dose assays. Risk activity was assessed from volunteer responses to a clinician-administered questionnaire.

RESULTS: Moderate-severe systemic symptoms were reported in 24/256 (9%) and moderate-severe local pain and tenderness occurred in 52/256 (20%) of vaccine-treated volunteers. There were no statistically significant differences in the frequency of these reactions between risk strata or treatment. Comparison of vaccine-induced neutralizing Ab responses revealed no significant differences among risk strata. After 3 and 4 immunizations, 89% and 91% of vaccinees had homologous neutralizing Ab; these responses were maintained over 6 months in a greater percentage after the fourth dose (84/116, 72%) than after the third dose (35/86, 41%). Combining all strata and comparing responses from baseline to months 19-24, 31/221 volunteers (14%) increased and 39/221 (18%) decreased number of sexual partners, and 27/221 volunteers (12%) increased and 45/221 (20%) decreased the number of unsafe sexual partner encounters. Preliminary analysis reveals similar trends at other time intervals.

CONCLUSIONS: In the first phase II HIV vaccine trial, the two rgp 120 vaccines demonstrated excellent safety in volunteers with diverse HIV-1 risks, and no differences in immune responses were noted among the 6 risk strata. Four rather than three immunizations may be optimal for eliciting sustained neutralizing Ab responses. Preliminary analysis indicates that participation in an HIV vaccine trial does not lead to significantly increased HIV risk behavior.

Keywords: AEGIS, HIV-1, AIDS Vaccines, HIV Antibodies, Risk-Taking, Vaccination, Immunity, HIV Seronegativity, Safety, Heterosexuality, Human, Male, Female, immunology, ICA11

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MoA284