Title |
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)
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Published in |
Journal of Infectious Diseases, May 2012
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DOI | 10.1093/infdis/jis342 |
Pubmed ID | |
Authors |
Ann Duerr, Yunda Huang, Susan Buchbinder, Robert W. Coombs, Jorge Sanchez, Carlos del Rio, Martin Casapia, Steven Santiago, Peter Gilbert, Lawrence Corey, Michael N. Robertson |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 9 | 19% |
Brazil | 3 | 6% |
South Africa | 1 | 2% |
India | 1 | 2% |
Germany | 1 | 2% |
Kenya | 1 | 2% |
Unknown | 32 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 43 | 90% |
Scientists | 2 | 4% |
Practitioners (doctors, other healthcare professionals) | 2 | 4% |
Science communicators (journalists, bloggers, editors) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Sweden | 1 | <1% |
Canada | 1 | <1% |
Unknown | 144 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 23% |
Student > Bachelor | 20 | 14% |
Researcher | 16 | 11% |
Student > Master | 15 | 10% |
Student > Doctoral Student | 13 | 9% |
Other | 19 | 13% |
Unknown | 29 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 36 | 25% |
Medicine and Dentistry | 27 | 18% |
Biochemistry, Genetics and Molecular Biology | 18 | 12% |
Immunology and Microbiology | 15 | 10% |
Nursing and Health Professions | 4 | 3% |
Other | 15 | 10% |
Unknown | 31 | 21% |