Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study).

The Journal of Infectious Diseases
Ann DuerrStep/HVTN 504 Study Team

Abstract

The Step Study tested whether an adenovirus serotype 5 (Ad5)-vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03-1.92; P= .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-...Continue Reading

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Citations

Oct 9, 2013·The New England Journal of Medicine·Scott M HammerUNKNOWN HVTN 505 Study Team
Dec 4, 2012·The Journal of Infectious Diseases·Thomas L Richie, Eileen F Villasante
Dec 4, 2012·The Journal of Infectious Diseases·Ann DuerrMichael N Robertson
Jan 18, 2013·Journal of Virology·Monica VaccariGenoveffa Franchini
Oct 3, 2012·Retrovirology·Per Johan Klasse, John P Moore
Nov 29, 2013·Viruses·N ManjunathPremlata Shankar
Jan 24, 2014·Virologica Sinica·Vladimir Temchura, Matthias Tenbusch
Oct 30, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nicola BorthwickTomáš Hanke
Dec 7, 2013·Nature Medicine·Andrew McMichaelDennis R Burton
Apr 5, 2014·Science·Anthony S FauciSusan P Buchbinder
Jul 22, 2014·Nature Immunology·Andrew PinceticJeffrey V Ravetch
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·George K LewisRobert C Gallo
Oct 8, 2014·Infectious Disease Clinics of North America·Paul Goepfert, Anju Bansal
Jun 8, 2013·Current Opinion in HIV and AIDS·Jean-Louis ExclerNina D Russell
May 11, 2013·Expert Review of Vaccines·José Esparza
Jun 8, 2013·Current Opinion in HIV and AIDS·Barton F Haynes, M Juliana McElrath
Aug 12, 2014·Viruses·Ralph A Tripp, S Mark Tompkins
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Haitao HuSilvia Ratto-Kim
Oct 30, 2015·Expert Review of Vaccines·Sayuri Seki, Tetsuro Matano
Oct 18, 2015·The Journal of Infectious Diseases·Stephen R WalshUNKNOWN HVTN 083 Study Group and the NIAID HVTN
Jan 20, 2016·Expert Review of Vaccines·Joshua J GlassRobert De Rose
Mar 22, 2016·Biophysics Reviews·Sean LalCristobal Dos Remedios
Nov 22, 2016·International Journal of Molecular Sciences·Zhiqing ZhangNingshao Xia
Jan 31, 2017·Immunological Reviews·Georgia D Tomaras, Stanley A Plotkin
Oct 5, 2019·Human Vaccines & Immunotherapeutics·Bette Korber, Will Fischer
Aug 6, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robbie B MailliardCharles R Rinaldo
Jan 5, 2013·The Open AIDS Journal·Missa P SanouJanet K Yamamoto
Jun 21, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Hong-Van TieuMagdalena E Sobieszczyk
Jul 30, 2014·Frontiers in Immunology·José Esparza, Marc H V Van Regenmortel

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