Follmann D, Gilbert P, Self S, Hudgens M, Gurwith M, Popovic V, Ackers M, Hu D, Flores J; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).
Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 106.
NIAID, NIH, DHHS, Bethesda, MD, USA
Backbround: VAX004, a randomized, double blind, placebo controlled, phase 3 trial of a bivalent rgp120 HIV-1 vaccine showed an overall null result in 5403 volunteers but raised the possibility that vaccine efficacy varied by race. We explored whether the results in racial subgroups were due to chance or an underlying explanation; risk behavior, immune response, or selective efficacy.METHODS: A risk score was constructed using 9 yes-or-no characteristics that predicted HIV infection risk. Immune response was measured for 8 types of antibodies in all infected vaccinees and a 5% random sample. Monte Carlo methods were used to make a multiplicity adjustment for subgroup p-values. Cox regression quantified risk by patient characteristics.RESULTS: Subgroups were well balanced at baseline. Overall, vaccine efficacy was 6% based on 368 infections. Vaccine efficacy for white, Hispanic, black, Asian, and other, were -7%, 15%, 67%, 66%, and 50%, suggesting a potential effect of the vaccine in certain subgroups. With a multiplicity correction, the adjusted p-value for VE in Nonwhites ranged from 0.08 to 0.13 and blacks ranged from 0.22 to 0.24. The vaccine trended towards increasing efficacy with increasing risk, vaccine efficacy = -48%, 3%, 43% by risk score = 0, 1-3, 4-9, p = 0.05 or 0.07 but whites engaged in riskier behavior average score 2.2/2.0 for white/nonwhite (p <0.01). Multivariable methods suggested that the average blocking of binding of the MN and GNE8 vaccine strains to CD4 best summarized immune response. Among vaccinees, the relative risks of infection were 1.00, 0.43, 0.34, and 0.29 (p <0.01) for the 4 quartiles of immune response. When the entire placebo group was used as a control the relative risks of infection were 1.67, 0.98, 0.87, and 0.74 suggesting immune response to vaccine might have identified inherent ability to avoid infection. Results appeared similar by race, but numbers were small. Selective efficacy of the vaccine was examined by classifying all infecting viruses as either similar (S) or not (DS) to strains used in the vaccine. The vaccine efficacy was 0%/19% for S/DS overall, 73%/24% in nonwhites and 83%/84% in blacks, (p = NS, 0.08, NS).CONCLUSIONS: Multiplicity adjusted p-values for race were >0.05. Though numbers were small, analyses of HIV risk behavior, antibody response, and type of infecting strain did not support any biologic explanation for differential vaccine efficacy by racial/ethnic subgroup. Higher measured humoral immune response may be associated with lower inherent risk of infection.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Clinical Trials as Topic
- Continental Population Groups
- Double-Blind Method
- European Continental Ancestry Group
- HIV Infections
- HIV Seropositivity
- Humans
- Placebos
- Risk-Taking
Other ID:
UI: 102270761
From Meeting Abstracts