A Novel Approach to Understanding Vaccine-Induced Seropositivity (VISP) in HIV Vaccine Clinical Trial Participants

Abstract

Vaccine-Induced Seropositivity (VISP) or Vaccine-Induced Seroreactivity (VISR) is emerging as a prominent cited reason for individuals declining participation in HIV vaccine clinical trials. As a result the progress towards an effective vaccine has been reduced. The VISP/VISR phenomenon refers to the appearance of seropositivity for HIV in individuals on screening enzyme immunoassays (ELISA) following receipt of the candidate HIV vaccine, although no patent HIV infection is present. This results in the individual being susceptible to social harms due to false positive HIV designation. This research endeavor introduces a continuous approach evaluating optical density values which will allow for a more informative way to view VISP/VISR. We analyzed optical density values from HIV Vaccine Trials Network (HVTN) studies (Protocol 065, 078, 204, and 077). Through this quantitative approach, we attempted to answer three questions: 1) How do optical density values vary between participants who received candidate HIV vaccines and those who receive placebos 2) How do the optical density values in HIV clinical trials participants vary with a vaccine regimen or enzyme immunoassay utilized 3) Is there dynamics concerning optical density values that can be ascertained overtime? This research endeavor looked at optical density values related to VISP/VISR in a continuous manner, a departure from the present dichotomous standards for designating VISP/VISR. This new approach offers an alternative view of VISP and consequentially will aid in mitigating VISP/VISR induced social harms for HIV vaccine clinical trials participants and offer a novel metric of the potential immunogenicity of the candidate HIV vaccines. Results: Analyses of the study protocols illustrate that there is a difference in optical density (OD) values between placebo and treatment groups in each study as expected (Wilcox signedrank test: p>.0001-.0096). The OD values in placebo recipients demonstrated limited variability and clustered tightly around 0.1-0.2. A difference in optical density values between treatment groups within each protocol was identified (Wilcox signed-rank test: p>.0001). It was also seen that OD values could distinguish between different enzyme immunoassays (Wilcox signed-rank test p>.0001). Additionally, the OD could distinguish between different order in HIV vaccine candidate regimen (p>.0001). Finally, it was seen that there was a significant difference in the average OD ratios in a selected study participants between specific time intervals in selected study participants.