Effect of rAd5-Vector HIV-1 Preventive Vaccines on HIV-1 Acquisition: A Participant-Level Meta-Analysis of Randomized Trials

PloS One
Yunda HuangPeter Gilbert

Abstract

Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505, participants of all three studies were unblinded to their vaccination assignments during the study but continued follow-up. Rigorous meta-analysis can provide crucial information to advise the future utility of rAd5-vector vaccines. We included participant-level data from all three efficacy trials, and three Phase 1-2 trials evaluating the HVTN505 vaccine regimen. We predefined two co-primary analysis cohorts for assessing the vaccine effect on HIV-1 acquisition. The modified-intention-to-treat (MITT) cohort included all randomly assigned participants HIV-1 uninfected at study entry, who received at least the first vaccine/placebo, and the Ad5 cohort included MITT participants who received at least one dose of rAd5-HIV vaccine or rAd5-placebo. Multivariable Cox regression models were used to estimate hazard ratios (HRs) of HIV-1 infection (vaccine vs. placebo) and evaluate HR variation across va...Continue Reading

References

Oct 31, 2002·Statistics in Medicine·Paula R WilliamsonAnthony G Marson
Nov 17, 2006·The Journal of Infectious Diseases·Andrew T CatanzaroUNKNOWN Vaccine Research Center 006 Study Team
Nov 17, 2006·The Journal of Infectious Diseases·Barney S GrahamUNKNOWN Vaccine Research Center 004 Study Team
Feb 28, 2007·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jorge A TavelBarney S Graham
Mar 30, 2007·Vaccine·Andrew T CatanzaroUNKNOWN VRC 007 Study Team
Apr 25, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Frances H PriddyUNKNOWN Merck V520-016 Study Group
Nov 18, 2008·Lancet·M Juliana McElrathUNKNOWN Step Study Protocol Team
Dec 26, 2008·AIDS Research and Human Retroviruses·Clayton D HarroUNKNOWN Merck V520-007/012 Study Teams
Feb 9, 2010·BMJ : British Medical Journal·Richard D RileyGhada Abo-Zaid
Sep 22, 2010·AIDS Research and Human Retroviruses·Ouzama NicholsonUNKNOWN for the Merck V520-018/HIV Vaccine Trials Network 050 Study Team
Aug 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen C De RosaUNKNOWN National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network
Dec 29, 2011·The Journal of Clinical Investigation·Nicole FrahmM Juliana McElrath
Jul 17, 2013·Clinical and Experimental Vaccine Research·Youngjoo Choi, Jun Chang
Oct 9, 2013·The New England Journal of Medicine·Scott M HammerUNKNOWN HVTN 505 Study Team
Feb 25, 2014·The Lancet Infectious Diseases·Glenda E GrayUNKNOWN HVTN 503/Phambili study team

❮ Previous
Next ❯

Methods Mentioned

BETA
circumcision

Software Mentioned

Step
Ovid Medline
Phambili
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.