VISP/R Meeting Summary - Global HIV Vaccine Enterprise
Transcription
VISP/R Meeting Summary - Global HIV Vaccine Enterprise
VISP/R Meeting Summary Robert W Coombs MD PhD FRCPC University of Washington, Seattle, WA [email protected] Introduction • Mary Marovich (NIH) • The Vaccine-induced seropositivity/reactivity issue – Scope: Volunteer participation; Enrollment; Safety/stigma; Public perception; Diagnosis and study endpoints – Magnitude: Will increase with more immunogenic vaccines; increased testing intensity and follow-up; Cost escalation with NAT; Monitoring frequency post-study – Conclusion: All aspects of vaccine research are clearly affected by VISP/R! 3/15/13 VISP/SR Meeting Summary 2 Vaccine candidate pipeline • Barney Graham (NIH VRC) • Back to the future…an historical HIV vaccine perspective with evolution of outcome from antibody to cellular response to antibody response • Conclusions: – Antigen content of vaccines more complex; as such VISP/R will increase – Commonly used serological tests can’t distinguish suppressed HIV infection from vaccine-induced response – Peptide-based serological testing helps to discriminate vaccineassociated antibody responses from infection but requires collaboration between kit manufactures, vaccine developers and the various regulatory agencies 3/15/13 VISP/SR Meeting Summary 3 HIV Diagnostic Algorithms • Sheila Peel (US Military HIV Research Program) • Overview of US Military HIV-testing algorithm • Emphasis on testing for HIV DNA and RNA given that RNA may be suppressed for a number of reasons • Symantec clarification of “misclassification” from “false-positive” serological testing results • Orthogonal testing adds to algorithm specificity but also redraw and retest is important • No FDA-approved HIV-1 DNA or HIV-2 NAT assays are available for the next-generation HIV diagnostic algorithm • The appropriate HIV diagnostic algorithm for resource limited settings will be driven by what testing platforms are available 3/15/13 VISP/SR Meeting Summary 4 HVTN VISP/R Practices • John Hural (UW HVTN) • HVTN has a long-term commitment to providing VISP/R services, which influences – – – – – Kit selection for each protocol Algorithm design Endpoint adjudication (Web-based; results in 24 hours) End of study seroreactivity (EOS) VISP protocol (HVTN 091) • Post study testing • VISP Registry • Conclusion: Need for “less sensitive” FDA-approved serological kits for protocols; When does cost of testing algorithm exceed cost of running NAT PCR on all vaccine recipients for diagnosis of infection? Still need to deal with community level HIV testing algorithms for post-study testing. 3/15/13 VISP/SR Meeting Summary 5 HVTN Post-study testing services • • • • Carissa Karg (UW HVTN) Testing service in place for 2.5 years (HVTN 910) Objective is to mitigate social harm from VISP/R Challenges: providing local phlebotomy service; State guidelines for consent/testing/reporting; confirm prior study participation (hence, registry); • 3 hours administrative time per participant at a cost of $500; 3/15/13 VISP/SR Meeting Summary 6 HVTN VISP Registry (cont’d) • Secure web-based data base (ATLAS) • Projected to have >8000 registrants • Registry will facilitate – More efficient post-study testing services – Identify specimens for test optimization – Study vaccine breakthrough infection 3/15/13 VISP/SR Meeting Summary 7 Current VISP/R practice overview • Mary Allen(DAIDS, Vaccine Clinical Research Branch) • Participants 14 question survey of 9 vaccine research groups • Inconsistencies in some VISP/R-related services: – Awareness of social impact of VISP/R; collect data on durability of VISP; publish experience; long-term contact with post-study participants; offer remote HIV testing; information about effect of study participation and VSIP/R on blood donations 3/15/13 VISP/SR Meeting Summary 8 Best practices discussion • • • • • • • • • Pat Fast (International AIDS Vaccine Initiative) Informed consent IRB/Ethical/Regulatory concerns Effect of VISP/R on recruitment Social harms Long-term follow-up Public health interference Vaccine design Several issues raised during discussion – Cyber security of VISP/R data bases – Self-testing and implications for blinding; participation in overlapping studies; participation in VISP/R registries associated with some complexities for vaccine subjects in different countries 3/15/13 VISP/SR Meeting Summary 9 Pipeline of diagnostic tests • Mark Ware (Clinton Health Access Initiative) • Number of emerging near-patient tests with following characteristics: – – – – – – – – – – – – Small and portable Decreased turn-around-time for results Low throughput High limit of detection Small sample size Whole blood (Early infant diagnosis) Integration of sample preparation & detection Quantitative/qualitative flexibility Connectivity to internet and 3G for data transmission to central data bases Ease of use and training Seeking regional approval, WHO prequalification and CE Mark Need blinded head-to-head comparisons and participation in EQA programs • A standardized regulatory approach to assay approval in resource-limited countries would assist with assay development and deployment 3/15/13 VISP/SR Meeting Summary 10 Challenges in developing & commercializing HIV test that differentiate VISP • Chris Bentsen (Bio-Rad Laboratories) • Overview of FDA regulatory complexities and why developing VISP/R-specific HIV antibody tests is not cost-effective for large diagnostic companies • Bio-Rad has only 10/39 diagnostic assays in US • Summarized four FDA-approved HIV tests (WB, Plus O, Multispot, Combo Ag/Ab 4th generation assay) • Described Geenius HIV1/2 as eventual replacement for Multispot assay 3/15/13 VISP/SR Meeting Summary 11 Developing a commercial VISP test: SELECTEST experience • Andrew Levin (Immunetics, Inc.) • Application of antigen discovery and peptide design to develop a specific assay for VISP, based on gp41 peptides not found in vaccines • In population with prevalence of 0.7%, SELECTEST has a PPV of 58%; NPV 99.9%; in combination with WB, PPV of 98.5% • Fewer misclassifications (VSIP/SR) in HIV vaccine trials thus far compared to commercial platforms 3/15/13 VISP/SR Meeting Summary 12 Simple AMplification Based Assay (SAMBA) • Helen Lee (University of Cambridge, UK) • Isothermal HIV-1 2LTR target amplification with signal amplification • Comparable to Roche COBAS AMP/COBAS TM v2.0 • Whole blood (EID) and plasma (monitoring treatment); combined specimen preparation and amplification • POC test: No cold chain; requires AC power source; deployed for evaluation trials internationally 3/15/13 VISP/SR Meeting Summary 13 Roundtable on VISP/SR & diagnostic tests • Bob Coombs, Helen Lee, Michele Owen, Marco Schito, Mark Ware • Potential for decreased VSIP/SR by using orthogonal tests that can interrogate the vaccine-associated immunoblot profile (e.g., Geenius) • Need data on vaccine performance of 4th generation EIA/CLIA • Complex HIV seroreactivity patterns arising from complex env-gag vaccine regimens and requirement for complementary HIV-1 nucleic acid testing in testing algorithms but limitations noted in absence of FDA-approved HIV DNA test and labeling restrictions on some commercial HIV RNA assays • Potential attenuating effects of pre- and/or post-exposure antiretroviral prophylaxis on detection of HIV infection -- antibody, RNA and DNA -- in vaccine trials requires further study 3/15/13 VISP/SR Meeting Summary 14 VISP/R Terminology • Helene Zinszner (Global HIV Vaccine Enterprise) • A community focus group was conducted to evaluate the use of the term “VISP/SR” • Outcome: A kindler and gentler phrase/acronym to replace the VISP/SR “phenomenon” that also confers a more positive message is needed… 3/15/13 VISP/SR Meeting Summary 15