Evidence map›Paper›PMID 29649264›Full record

ArticlePloS one2018

Age at antiretroviral therapy initiation and cell-associated HIV-1 DNA levels in HIV-1-infected children.

Louise Kuhn, Maria Paximadis, Bianca Da Costa Dias, Shayne Loubser, Renate Strehlau, Faeezah Patel, Stephanie Shiau, Ashraf Coovadia, Elaine J Abrams, Caroline T Tiemessen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 5% 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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. HIV-1 reservoir evolution in infants infected with clade C from Mozambique.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023
    Article
  15. Article
  16. HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022
    Review
  17. Significance of initiating antiretroviral therapy in the early stage of HIV infection.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022
    Article
  18. Review
  19. Article
  20. Article
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

10 authors at 1 institution in 2 countries.

Louise KuhnGertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0002-2305-8665
Maria PaximadisCentre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
Bianca Da Costa DiasCentre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
Shayne LoubserCentre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
Renate StrehlauEmpilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Faeezah PatelEmpilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Stephanie ShiauGertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
Ashraf CoovadiaEmpilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Elaine J AbramsDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Caroline T TiemessenCentre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.ORCID 0000-0002-0991-1690
University of the Witwatersrand · ZA

Funding

Early neonatal treatment and immune quiescenceU01HD080441 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KUHN, LOUISE · 2014 to 2018
$5.1M
Host epigenetic and mitochondrial function in HIV-infected childrenR01HD073952 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KUHN, LOUISE · 2012 to 2016
$3.7M
Bone health in perinatally HIV-infected South African children on antiretroviralsR01HD073977 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARPADI, STEPHEN M, YIN, MICHAEL T · 2012 to 2016
$3.6M
Treatment Options for Protease Inhibitor Exposed ChildrenR01HD061255 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KUHN, LOUISE · 2010 to 2014
$2.9M
NICHD NIH HHS R01 HD061255NICHD NIH HHS R01 HD073952NICHD NIH HHS R01 HD073977NICHD NIH HHS U01 HD080441NIH HHS HD061255NIH HHS HD073952NIH HHS HD073977NIH HHS HD080441
6 · The paper itself

Abstract

backgroundThe latent viral reservoir is the major obstacle to achieving HIV remission and necessitates life-long antiretroviral therapy (ART) for HIV-infected individuals. Studies in adults and children have found that initiating ART soon after infection is associated with a reduction in the size of the HIV-1 reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but currently older HIV-infected children suppressed on ART.

methodsThe study participants comprised of a cohort of 146 early-treated children with HIV-1 RNA <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa. A stored buffy coat sample collected after a median 4.3 years on ART and where HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect total HIV-1 subtype C proviral DNA was used. Children were followed prospectively for up to 3 years after this measurement to investigate subsequent HIV-1 RNA rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline prior to HIV-1 DNA measurement and other factors were investigated.

resultsA gradient between age at ART initiation and later HIV-1 DNA levels was observed. When ART was started <2 months of age, the lowest levels of cell-associated HIV-1 DNA (median 1.4 log10copies/106 cells, interquartile range [IQR] 0.95-1.55) were observed compared to ART started at 2-4 months (median 1.68, IQR 1.26-1.97) or 5-14 months of age (median1.98, IQR 1.69-2.25). A low CD4 T-cell count pre-treatment predicted higher levels of HIV-1 DNA on later testing. The probability of HIV-1 RNA rebound >50 copies/ml whilst on ART within 3 years after the DNA measurement was 2.07 (95% CI: 1.352-3.167) times greater if the HIV-1 DNA level was above the median of 55 copies/106 cells.

conclusionsCell-associated HIV-1 DNA levels measured after more than 4 years on ART were lower the younger the age of the child when ART was initiated. This marker of the size of the viral reservoir also predicted subsequent viral rebound/treatment failure while ART was sustained. The results provide additional evidence of the benefits of prompt diagnosis and early ART initiation in newborns and infants.

Indexed as

Age FactorsAnti-HIV AgentsChild, PreschoolCohort StudiesDNA, ViralFemaleHIV-1HIV InfectionsHumansMaleProportional Hazards ModelsTime FactorsTreatment FailureAnti-HIV AgentsDNA, Viral

Identifiers

PMID29649264
PMCPMC5896970
OpenAlexW2797581063

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.