Evidence map›Paper›PMID 31415590›Full record

ArticlePloS one2019

Genetic and clinical predictors of CD4 lymphocyte recovery during suppressive antiretroviral therapy: Whole exome sequencing and antiretroviral therapy response phenotypes.

Ruth Greenblatt, Peter Bacchetti, Ross Boylan, Kord Kober, Gayle Springer, Kathryn Anastos, Michael Busch, Mardge Cohen, Seble Kassaye, Deborah Gustafson and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 25% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Observational
  4. Article
  5. Article
  6. Article
  7. Review
  8. Identification of CD8AIDS research and therapy · 2022
    Article
  9. Article
  10. 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

12 authors at 7 institutions in 1 country.

Ruth GreenblattUCSF School of Pharmacy, Department of Clinical Pharmacy, San Francisco, CA, United States of America.
Peter BacchettiUCSF School of Medicine, Department of Epidemiology and Biostatistics, San Francisco, CA, United States of America.
Ross BoylanUCSF School of Medicine, Department of Epidemiology and Biostatistics, San Francisco, CA, United States of America.
Kord KoberUCSF School of Nursing, Department of Physiological Nursing, San Francisco, CA, United States of America.ORCID 0000-0001-9732-3321
Gayle SpringerJohns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, United States of America.
Kathryn AnastosAlbert Einstein College of Medicine and Montefiore Health Systems, Bronx, NY, United States of America.
Michael BuschUCSF School of Medicine, Department of Epidemiology and Biostatistics, San Francisco, CA, United States of America.
Mardge CohenStroger Hospital, Chicago, IL, United States of America.
Seble KassayeGeorgetown University Medical Center, Department of Medicine, Washington, DC, United States of America.
Deborah GustafsonState University of New York, Downstate Medical Center, Department of Neurology, Brooklyn, NY, United States of America.
Bradley AouizeratNew York University School of Dentistry and Bluestone Center for Clinical Research, NY, NY, United States of America.ORCID 0000-0002-6047-9397
Women’s Interagency HIV Study
University of California, San Francisco · USAlbert Einstein College of Medicine · USCenter for Clinical Research (United States) · USGeorgetown University · USJohn H. Stroger, Jr. Hospital of Cook County · USJohns Hopkins University · USState University of New York · US

Funding

Women's Interagency HIV Study (WIHS-V)U01AI035004 · NIAID · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI ANASTOS, KATHRYN M., SHARMA, ANJALI · 1993 to 2018
$65.7M
WOMEN'S INTERAGENCY HIV STUDY ORGANIZATION, MANAGEMENT AND COMMUNICATIONSU01AI034989 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AOUIZERAT, BRADLEY E, GREENBLATT, RUTH MARTHA · 1993 to 2018
$65.6M
Women's Interagency HIV Study (WIHS) IIIU01AI031834 · NIAID · SUNY DOWNSTATE MEDICAL CENTER · PI GUSTAFSON, DEBORAH R., MINKOFF, HOWARD · 1998 to 2018
$53.5M
WOMEN'S INTERAGENCY HIV STUDY (WIHS) ORGANIZATION AND MANAGEMENTU01AI034994 · NIAID · GEORGETOWN UNIVERSITY · PI KASSAYE, SEBLE G · 1993 to 2018
$52.0M
Women's Interagency HIV Study (WIHS) IV, Chicago ConsortiumU01AI034993 · NIAID · HEKTOEN INSTITUTE FOR MEDICAL RESEARCH · PI COHEN, MARDGE H, FRENCH, AUDREY · 1994 to 2018
$51.0M
WIHS DATA MANAGEMENT AND ANALYSIS CENTER(WDMAC)U01AI042590 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GANGE, STEPHEN J, GOLUB, ELIZABETH T · 1998 to 2018
$38.4M
NIAID NIH HHS U01 AI031834NIAID NIH HHS U01 AI034989NIAID NIH HHS U01 AI034993NIAID NIH HHS U01 AI034994NIAID NIH HHS U01 AI035004NIAID NIH HHS U01 AI042590
6 · The paper itself

Abstract

Increase of peripheral blood CD4 lymphocyte counts is a key goal of combined antiretroviral therapy (cART); most, but not all, recipients respond adequately and promptly. A small number of studies have examined specific genetic factors associated with the extent of CD4 recovery. We report a genome-wide examination of factors that predict CD4 recovery in HIV-infected women. We identified women in in a cohort study who were on cART with viral load below 400 copies, and drew racially and ethnically matched samples of those with good CD4 response over 2 years or poor response. We analyzed the exomes of those women employing next generation sequencing for genes associated with CD4 recovery after controlling for non-genetic factors identified through forward stepwise selection as important. We studied 48 women with good CD4 recovery and 42 with poor CD4 recovery during virologically-suppressive cART. Stepwise logistic regression selected only age as a statistically significant (p<0.05) non-genetic predictor of response type (each additional year of age reduced the odds of good recovery by 11% (OR = 0.89, CI = 0.84-0.96, p = 0.0009). After adjustment for age and genomic estimates of race and ethnicity, 41 genes harbored variations associated with CD4 recovery group (p≤0.001); 5 of these have been previously reported to be associated with HIV infection, 4 genes would likely influence CD4 homeostasis, and 13 genes either had known functions or were members of product families that had functions for which interactions with HIV or effects on lymphocyte homeostasis were biologically plausible. Greater age was the strongest acquired factor that predicted poor CD4 cell recovery. Sequence variations spanning 41 genes were independently predictive of CD4 recovery. Many of these genes have functions that impact the cell cycle, apoptosis, lymphocyte migration, or have known interactions with HIV. These findings may help inform new hypotheses related to responses to HIV therapy and CD4 lymphocyte homeostasis.

Indexed as

Exome SequencingPhenotypeAdultAnti-HIV AgentsCD4 Lymphocyte CountFemaleHIV InfectionsHumansMaleMiddle AgedTreatment OutcomeViral LoadAnti-HIV Agents

Identifiers

PMID31415590
PMCPMC6695188
OpenAlexW2968552908

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.