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)

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; parti...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2012-07, Vol.206 (2), p.258-266
Main Authors: Duerr, Ann, Huang, Yunda, Buchbinder, Susan, Coombs, Robert W., Sanchez, Jorge, del Rio, Carlos, Casapia, Martin, Santiago, Steven, Gilbert, Peter, Corey, Lawrence, Robertson, Michael N.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - immunology
Adenoviridae Infections - complications
Adenovirus
Adult
AIDS
AIDS Vaccines - adverse effects
AIDS Vaccines - genetics
AIDS Vaccines - immunology
Applied microbiology
Biological and medical sciences
Circumcision, Male
Experimentation
Female
Fundamental and applied biological sciences. Psychology
Genetic Vectors
HIV
HIV 1
HIV infections
HIV Infections - etiology
HIV Infections - prevention & control
HIV Infections - transmission
HIV-1 - immunology
HIV/AIDS
Human immunodeficiency virus
Humans
Infections
Infectious diseases
Major and Brief Reports
Male
Medical sciences
Microbiology
Miscellaneous
Placebos
Proportional Hazards Models
Research facilities
Risk Factors
Sexual Behavior
Time Factors
Vaccination
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Synthetic - adverse effects
Vaccines, Synthetic - immunology
Viral Load
Virology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Clinical Trials Registration. NCT00095576.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jis342