Important note: Information in this article was accurate in October 2001. The state of the art may have changed since the publication date. IAVI Report - October - November 2001
As Thailand prepares for Phase III testing of a prime-boost vaccine strategy in 2002 (see article), the US HIV Vaccine Trials Network (HVTN) is developing efficacy trial plans for a similar canarypox-gp120 combination starting in 2003. In Philadelphia, Susan Buchbinder (San Francisco Department of Public Health), HVTN protocol co-chair, described the HVTN study, its differences to the Thai trial in terms of design, goals, study population and the vaccine itself, and the ongoing process for what could be a controversial decision on whether to move forward.
The HVTN trial will use Aventis Pasteur's vCP1452, a later-generation HIV-canarypox vaccine based on subtype B (the predominant subtype in the Americas, where the trial will take place) and containing HIV env, gag and pol (as in the clade E-based Thai study), plus additional T-cell epitopes from nef and pol. The three-arm trial will test vCP1452 with and without a boost of VaxGen's gp120 subunit (clade B) in an 11,000-person cohort, and also includes a placebo arm (3:3:2 ratio). Beyond looking for protection against HIV infection or disease, volunteers will be monitored for vaccine-induced immune responses and, in those who become infected, for viral load in blood and genital secretions. The goal: to establish correlates of protection, even if the vaccine(s) proves to have only very low (10-20%) efficacy.
Success on that front—which would be an enormous boon for design and evaluation of future AIDS vaccine candidates—will depend largely on having enough statistical power built into the trial. That, in turn, has driven the setting of specific immunogenicity criteria by which the go-no go decision will be made, based on results of a just-completed Phase II trial (HVTN 203) with 330 volunteers. Buchbinder spelled these out: 36% of vaccinees showing HIV-specific CD8+ cytotoxic T-lymphocytes (CTL) at day 182, or 47% at either day 98 or day 182.
Another key factor in the impending decision is finding appropriate study populations, as well as committed investigators and governments in countries where HIV subtype B predominates. The plan is to enroll high-risk heterosexuals and men who have sex with men, both from high-enough incidence populations that trial endpoints can be evaluated separately for these two groups. So far, numerous HVTN sites in the US are on board, along with those in Peru, Brazil, Haiti and Trinidad and Tobago. Other potential sites across the Americas are now being evaluated.
In the early months of 2002, HVTN investigators and scientists at the National Institute of Allergy and Infectious Disease will be looking at the Phase II data and making their decision. Some outside researchers question the merits of going forward, especially with two trials, while others see useful differences in the two approaches, provided that ongoing discussions on pooling and comparing data pan out. Watch this space. —P.K.
011010
IAVI2001-1010
©2001. The IAVI Report.
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2001. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.
