INTERMEDIATE-SIZE TRIALS FOR THE EVALUATION OF HIV VACCINE CANDIDATES- A WORKSHOP SUMMARY

There has been considerable debate over what evidence from preclinical and clinical studies is required to advance an HIV vaccine candidate to phase III efficacy testing. Given this situation, conduct of interm ediate-size trials is proposed as a method for assessing the plausibil ity that a vaccine candidate would prevent chronic HIV infection. Desi gned to observe 45 incident infections in the control group, these pre liminary efficacy trials could rule out candidates with low or no effi cacy while advancing those candidates with some evidence of protection to definitive trials. In addition, these trials could provide clues a bout correlates of immunity. A threefold or greater difference in the postvaccination geometric mean titer of neutralizing antibody can be r eadily detected between infected and uninfected vaccinees. Differences in CD8(+) cytotoxic T lymphocytes, however, are more difficult to det ect. Intermediate-size trials could also discern a 0.5 log10 or greate r difference in plasma HIV-1 RNA levels between infected vaccinees and infected controls. Such differences in viral load might suggest disea se amelioration or reduction in infectiousness. Given the large variab ility in CD4 count and its relatively modest average decline in the ye ar after infection, a slower decline in CD4 count among infected vacci nees would not be detectable. With limited resources, intermediate-siz e trials could contribute significantly to HIV vaccine development.