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Sieve analysis in HIV-1 vaccine efficacy trials

Edlefsen, Paul T.; Gilbert, Peter B.; Rolland, Morgane

doi: 10.1097/COH.0b013e328362db2b
CHANGING ENVIRONMENT IN HIV VACCINE: Edited by Nelson L. Michael and Glenda Gray

Purpose of review: The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine.

Recent findings: The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses.

Summary: Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

aStatistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

bU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring

cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA

Correspondenceto Morgane Rolland, Ph.D, Chief, Viral Genetics section, U.S. Military HIV Research Program (MHRP); HJF, 503 Robert Grant Avenue, Room 2A46, Silver Spring, MD 20910, USA. Tel: +1 301 319 2099; fax: +1 301 319 7684; e-mail: mrolland@hivresearch.org

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