Summary of Abstracts Presented on AIDSVAX at the XIII International Conference in Durban
July 9-14, 2000
A phyase I/II study of bivalent gp120 (AIDSBAX B/E) was conducted in Bangkok, Thailand among 92 HIV-negative volunteers. The results demonstrated that the vaccine is safe, well tolerated, and induced strong and specific immune responses to each of the two gp120 antigens (B and E). The results suppored proceeding to phase III efficacy trials in Thailand.
A phase I/II open label trial of AIDSVAX B/B and B/E was conducted in the U.S. among 122 HIV-negative volunteers. 100% of volunteers developed strong antibody responses with the most commone side effect being pain and tenderness at the injection site. These results supported proceeding to phase III efficacy trials in North America and Thailand.
AIDSBAX B/E is a vaccine that was designed specifcally to address the type of HIV that is epidemic in Thailand. Earlier studies have shown that the vaccine was safe and induced a strong immune response. A phase III trial has ben initiated to test the effectiveness of the vaccine in preventing HIV infections in humans. So far, recruitment is procedding well, follow-up has been excellent and adverse effects have been minimal.
A phase III study of AIDSVAX B/E was initiated among injection drug users in Bangkok. The volnteers are mostly male, young (mean age 30.6 yeras) and have at least a primary aducation. Almost all inject heroin on a regular or sporadic bases and 30% have reported sharing needles. The primary motivation ot participate is altruism. Thus far, retention rates and immunization compliance have been excellent.
HIV vaccine trial participants may be subject to social harms such as stigmatization, misclassification of HIV infection status or incrased risk-behavior. Very few social harms (5) have been reported wth respect to personal relationship disturbances and only one incident was reported with respect to employment. Injection drug use has dropped from 96% to 83% and sharing needles dropped from 30% to 14%.
A phase III, double-blind, placebo-controlled trial was initiated among 5,318 at-risk volunteers to test the efficacy of AIDSVAX B/B. The volunteers are primarily men (94%), white (83%) and educated. Altuism is the primary motivation for enrolling. Baseline sexual behavior for men who have sex with men (MSM) indicates that 54% had 5 or more sexual partners and 44% with HIV+ partners in the last 6 months. So far, retention has been excellent and there have been no serious adverse events related to the vaccine.
Phase II studies suggest that HIV vaccine trial volunteers may experience stigmatization, discrimination (from false-positive HIV tests), and incrased risk-taking behavior. A comprenensive program to address these concerns was integrated into the first Phase III HIV vaccine trial. So far, disturbances in personal relationships were the most frequently reported social harm and employment and insurance related issues have been infrequent. No increasing trendin reisk behavior has been observed to date.
Historcally, problems of virus variation were solved by the develpment of multivalent vaccines using antigens dereived from different virus strains. We have used this approach to develop bivalent vaccines for use in North America and Sougheast Asia. By combining two gp120 antigens in each formulation (AIDSVAX B/B and B/E), we have been able to increase the breadth of antibody response and demonstrate neutralization of primary isolates.
A major concern in HIV vaccine trails is the possibility that volunteers will test false positive for HIV infection. Historically, the risk was low, but new HIV testing kits are reported to have been supplemented with envelope peptides. Kits that contain envelope peptides yield a higher false positive rate (up to 25%) compared to other kits (up to 30%). However, there is little chance of a misclassification of HIV infection in the antibody test is followed with a confirmatory immunoblot.