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)
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P=1.0) over all follow-up time. CONCLUSIONS: The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination.
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Adenovirus can increase susceptibility to HIV-1 infection.
“However, several studies show that adenovirus can increase the susceptibility to HIV-1 infection [56,57].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [56]
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- Authors
- Duerr, A., Huang, Y., Buchbinder, S., Coombs, R. W., Sanchez, J., del Rio, C., Casapia, M., Santiago, S., Gilbert, P., Corey, L., Robertson, M. N., & for the Step/HVTN 504 Study Team
- Affiliations
- University of Washington (US)
- San Francisco Department of Public Health (US)
- Care Resource (US)
- Corresponding author
- Duerr, A.
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-04
- Volume
- 206
- Issue
- 2
- Pages
- 258-266
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3490694
- OpenAlex
- W2116834921
- Cited by
- 210
- References
- 23
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 13 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 16 · 2016: 24 · 2015: 22 · 2014: 33 · 2013: 28 · 2012: 9
- FWCI
- 13.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- University of Pennsylvania
- Emory University
- University of Washington
- University of Rochester
- University of Ottawa
- Saint Louis University
- York University
- Department of Science and Technology, Ministry of Science and Technology, India
- University of New South Wales
- Women's College Hospital
- University of Toronto
- Université de Montréal
- Universidade de São Paulo
- Universidade Federal do Rio de Janeiro
- National Institutes of Health (AI068614)
- University of Illinois at Urbana-Champaign
- School of Medicine, New York University
- Weill Cornell Medical College
- School of Medicine, Emory University
- National Institute of Allergy and Infectious Diseases (AI068614, UM1AI068614, R37AI054165)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- HIV vaccine, STEP study, HIV acquisition, male circumcision, HIV prevention
- MeSH terms
- Adenoviridae, Adenoviridae Infections, Adult, Circumcision, Male, Female, Genetic Vectors, Humans, Male, Risk Factors, Sexual Behavior, Time Factors, Vaccines, Synthetic, HIV-1, HIV Infections, Proportional Hazards Models, AIDS Vaccines, Viral Load
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