Evidence map›Paper›PMID 26951820›Full record

ArticleThe Journal of infectious diseases2016

Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02.

Ellen M Leitman, Jacob Hurst, Masahiko Mori, James Kublin, Thumbi Ndung'u, Bruce D Walker, Jonathan Carlson, Glenda E Gray, Philippa C Matthews, Nicole Frahm and 1 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00413725 (A Multicenter Double-Blind Randomized Placebo-Controlled Phase IIB Test-of-Concept Study to Evaluate the Safety and Efficacy of a Three-Dose Regimen of the Clade B-based Merck Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine in HIV-1 Uninfected Adults in South Africa), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00413725 phase2completednot on this map

A Multicenter Double-Blind Randomized Placebo-Controlled Phase IIB Test-of-Concept Study to Evaluate the Safety and Efficacy of a Three-Dose Regimen of the Clade B-based Merck Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine in HIV-1 Uninfected Adults in South Africa

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2007 to 2012Enrolled801ConditionsHIV InfectionsArmsMRKAd5 HIV-1 gag/pol/nef, Placebo
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Role of HIV-specific CD8The Journal of experimental medicine · 2017
    Article
  6. Current views on the potential for development of a HIV vaccine.Expert opinion on biological therapy · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 4 countries.

Ellen M LeitmanDepartment of Paediatrics.
Jacob HurstNuffield Department of Medicine, University of Oxford, United Kingdom.
Masahiko MoriDepartment of Paediatrics.
James KublinHIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
Thumbi Ndung'uRagon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal KwaZulu-Natal Research Institute for Tuberculosis and HIV-1, University of KwaZulu-Natal, Durban Max Planck Institute for Infection Biology, Berlin, Germany.
Bruce D WalkerRagon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.
Jonathan CarlsoneScience Group, Microsoft Research, Redmond, Washington.
Glenda E GraySouth African Medical Research Council, Cape Town Perinatal HIV-1 Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Philippa C MatthewsNuffield Department of Medicine, University of Oxford, United Kingdom.
Nicole FrahmHIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle.
Philip J R GoulderDepartment of Paediatrics HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.
University of KwaZulu-Natal · ZAUniversity of Oxford · GBCancer Research Center · USFred Hutch Cancer Center · USMicrosoft (United States) · USPerinatal HIV Research Unit · ZARagon Institute of MGH, MIT and Harvard · US

Funding

LOC: HIV Vaccine Trials NetworkUM1AI068614 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Dan H. Barouch, Lawrence Corey · 2011 to 2026
$1175.6M
LC: HIV Vaccine Trials NetworkUM1AI068618 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Margaret Juliana McElrath · 2011 to 2026
$483.6M
SDMC: HIV Vaccine Trials NetworkUM1AI068635 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Peter B. Gilbert, Yunda Huang · 2011 to 2026
$385.9M
Leadership Group for a Global HIV Vaccine Clinical Trials NetworkU01AI068614 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COREY, LAWRENCE · 2006 to 2010
$181.5M
HVTN Laboratory ProgramU01AI068618 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MCELRATH, MARGARET JULIANA · 2006 to 2010
$82.6M
Leadership for HIV/AIDS Clinical Trials Networks; HIV Vaccine Trials NetworkU01AI068635 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SELF, STEVEN G. · 2006 to 2010
$53.8M
Soweto Clinical Trials UnitUM1AI069453 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI Glenda E Gray, Lerato Mohapi · 2012 to 2026
$40.9M
University of KwaZulu-Natal - CAPRISA HIV/AIDS Clinical Trials UnitU01AI069469 · NIAID · UNIVERSITY OF KWAZULU-NATAL · PI ABDOOL KARIM, SALIM S · 2007 to 2011
$28.0M
Soweto Clinical Trials UnitU01AI069453 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI GRAY, GLENDA · 2007 to 2011
$25.5M
Optimizing CD8+ T-cell responses against C clade HIV infection in subSaharan AfriR01AI046995 · NIAID · UNIVERSITY OF OXFORD · PI GOULDER, PHILIP J · 2000 to 2014
$6.8M
Cape Town Clinical Trials Unit (CT-CTU) for HIV/AIDS Prevention & TreatmentU01AI069519 · NIAID · UNIVERSITY OF CAPE TOWN · PI WOOD, ROBIN · 2007 to 2011
$4.6M
Howard Hughes Medical InstituteMedical Research Council G0501777NIAID NIH HHS R01 AI046995NIAID NIH HHS U01 AI068614NIAID NIH HHS U01 AI068618NIAID NIH HHS U01 AI068635NIAID NIH HHS U01 AI069453NIAID NIH HHS U01 AI069469NIAID NIH HHS U01 AI069519NIAID NIH HHS UM1 AI068614NIAID NIH HHS UM1 AI068618NIAID NIH HHS UM1 AI068635NIAID NIH HHS UM1 AI069453Wellcome TrustWellcome Trust WT104748MA
6 · The paper itself

Abstract

backgroundHLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent.

methodsViral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed.

resultsAmong those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4(+) T-cell count of <350 cells/mm(3) (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/10(6) peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients.

conclusionsIn addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4(+) T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition. CLINICAL TRIALS REGISTRATION: NCT00413725, DOH-27-0207-1539.

Indexed as

Viral LoadAdultAllelesCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunospot AssayFemaleHIV InfectionsHLA-B AntigensHumansMalePlacebosSAIDS VaccinesYoung AdultHLA-B58 antigenHLA-B AntigensPlacebosSAIDS VaccinesGag-specific CD8+ T cellsHIV-1 vaccineHLA class IPhambili trial

Identifiers

PMID26951820
PMCPMC4936641
OpenAlexW2337169759

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.