Following on the heels of the prior post, a new paper published online today in the Journal of Infectious Diseases confirms that uncircumcised MSM with pre-existing antibody responses to Ad5 experienced an enhanced risk of HIV acquisition in the STEP trial. Importantly, however, this study documents that the effect has waned over time.
J Infect Dis. (2012)
First published online: May 4, 2012
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)
Ann Duerr1, Yunda Huang1, Susan Buchbinder2, Robert W. Coombs3, Jorge Sanchez4, Carlos del Rio5, Martin Casapia6, Steven Santiago7, Peter Gilbert1, Lawrence Corey1, Michael N. Robertson8 and for the Step/ HVTN 504 study team
1Fred Hutchinson Cancer Research Center, Seattle, WA
2San Francisco Department of Public Health, San Francisco, CA
3Departments of Laboratory Medicine & Medicine, University of Washington, Seattle, WA
4Asociacion Civil Impacta Salud y Educacion, Lima, Peru
5Department of Medicine, Emory University School of Medicine and Emory Center for AIDS Research, Atlanta, GA
6Asociacion Civil Selva Amazonica, Iquitos, Peru
7Care Resource, Miami, FL
8Merck Research Laboratories, West Point, PA
Background: The Step study tested whether an adenovirus serotype 5 (Ad5)-vectored HIV vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis non-efficacy criteria were met. Vaccinations were halted; participants were unblinded. In post-hoc analyses, more HIV infections occurred in vaccinees vs. placebo (V: P) recipients in men who had Ad5 neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition (V: P) over time.
Methods: We used cox proportional hazard models for analyses of vaccine effect on HIV acquisition and analysis of vaccine effect modifiers, and non-parametric and semi-parametric methods for analysis of constancy of relative risk over time.
Findings: 172 of 1836 men were infected. The adjusted V: P hazard ratio (HR) for all follow-up time was 1·40 (95% CI [1·03, 1·92], p=0·03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. 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.
Interpretation: The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination.