The importance of addressing VISP/R is growing as vaccines become more complex and immunogenic, especially in the context of ongoing and upcoming large efficacy trials. Commercially-available antibody tests are often unable to differentiate between VISP/R and true infection, requiring each trial sponsor to develop approaches and practices to address VISP/R during and post-study. The HIV vaccine field needs a coordinated and/or harmonized approach to VISP/R testing. Moreover, no single organization can take on the challenge of preparing for widespread use of a successful vaccine that induces VISP.
The Enterprise and partners held a convening at the Marriot Bethesda Suites Hotel in Bethesda, MD on 14 - 15 March 2013 around the issue of VISP/R. You can access the full report for the convening presentations from the links above.
Participants of the Enterprise convening on Vaccine Induced Sero-Positivity/Reactivity in Bethesda, MA, March 2013
- The Enterprise and partners held a webinar on 2 May 2013 to provide an update on the consultation. Click the link at the top of the page to access the audio recording of the webinar.
- A consultation organized by the Global HIV Vaccine Enterprise around Building consensus for a terminology for HIV vaccine-Induced Sero-Positivity/Sero-Reactivity *, led to the finding that it may not be possible or even practical at this time to seek a single term to use across the field of HIV Vaccine to describe the antibody response to HIV vaccine candidates that may be detected by diagnostic assays.
It may be more desirable to discriminate between several terms that coexist and leave the choice to the user depending on the context and the audience. We review existing and suggested terms and identify the nuances in potential use and applicability to various situations here: Vaccine Induced Sero-Positivity /Sero-Reactivity in participants of HIV vaccine clinical trials: Which term to use?
Representatives from the following agencies participated to the consultation: AgenceNationale de Recherche sur le SIDA- Vaccine Research Institute, France; AIDS Vaccine Advocacy Coalition, US; Canadian HIV Vaccine Initiative, Canada; China AIDS Vaccine Initiative, China; European and Developing Countries Clinical Trials Partnership, The Netherlands; HIV Vaccine Trials Network, US; International AIDS Vaccine Initiative, US; Military HIV Research Program, US; National Institute of Allergy and Infectious Diseases, US; National Institute of Health- Vaccine Research Center, US; World Health Organization.
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Organizing Committee for the March Convening
- Dr. Pat Fast, International AIDS Vaccine Initiative (IAVI), USA
- Ms. Mary Allen, National Institute of Allergy and Infectious Diseases (NIAID/NIH), USA
- Dr. Michael Busch, Blood Systems Research Institute, USA
- Dr. Uli Fruth, World Health Organization (WHO), Switzerland
- Dr. Hana Golding, US Food and Drug Administration (FDA), USA
- Dr. Surender Khurana, US Food and Drug Administration (FDA), USA
- Dr. Joseph Mulenga, Zamiba National Blood Transfusion Service, Zambia
- Dr. Sheila Peel, US Military HIV Research Program (MHRP), USA
- Dr. Marco Schito, National Institute of Allergy and Infectious Diseases (NIAID/NIH), USA
- Dr. Yegor Voronin, Global HIV Vaccine Enterprise, USA
- Formulate best practices for short- and long-term support of volunteers who develop VISP/R during trials.
- Share and summarize progress in developing commercially-available differential tests.
- Review current vaccine candidates from the point of view of development of appropriate differential HIV test(s).
- Explore opportunities for collaborations in addressing VISP.
HIV vaccine recipients may develop antibodies to HIV antigens leading to seropositivity on most commercially available HIV tests. These test results may lead to social stigma, restrictions on travel, employment and military service, difficulties in obtaining insurance, and ineligibility for blood or organ donations. Moreover, VISP complicates the detection of true HIV infection during and post study and requires one or more differential tests to accurately determine the participant’s HIV status. Individuals considering joining an HIV vaccine study list VISP as an important concern that influences their decision to participate in a trial1. Post-study testing poses particular challenges in regard to verification of study participation and vaccine receipt while maintaining participant confidentiality, in particular if study sites close or participants relocate. In addition, the frequent necessity of performing nucleic acid based testing is a further challenge. The issue of VISP is especially important for HIV vaccines moving toward licensure.
Currently, each trial sponsor develops its own approaches, norms and policies to address VISP, which may include:
- Providing information about VISP in Informed Consent Document and counseling
- Information brochures to explain VISP to participants and doctors;
- HIV testing algorithms and differential tests to accurately assess the HIV status;
- Plans and policies for post-trial testing of participants;
- Registries of trial participants;
- Study participant identification cards and toll-free telephone numbers to obtain assistance
- Certificates of trial participation to help explain the HIV-antibody positive status, when necessary.
- Direct assistance with VISP-related issues involving insurance applications, travel/immigration, and entry into the military.
For example, participants in NIAID-sponsored network trials worldwide are ensured access to VISP testing services for as long as needed. HVTN has created FAQs for volunteers, an information page for health care providers, and provides a contract VISP testing service for all US HVTN trial participants2.
There are ongoing efforts to develop and produce HIV tests that would reliably, quickly, and inexpensively distinguish VISP from HIV infection for current and future vaccine candidates 3,4.
If you have any questions or comments about the topic, please email Yegor Voronin.
- Cooper, C. J., Metch, B., Dragavon, J., Coombs, R. W. & Baden, L. R. Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients. JAMA 304, 275–283 (2010).
- Getting the Right Test for HIV.
- Khurana, S. et al. HIV-Selectest enzyme immunoassay and rapid test: ability to detect seroconversion following HIV-1 infection. J. Clin. Microbiol. 48, 281–285 (2010).
- Khurana, S. et al. Human immunodeficiency virus (HIV) vaccine trials: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies. J. Virol. 80, 2092–2099 (2006).
A compilation of additional resources on VISP/R is available to view and download here.