Evidence map›Paper›PMID 33387480›Full record

SynthesisThe lancet. HIV2021

Isoniazid preventive therapy plus antiretroviral therapy for the prevention of tuberculosis: a systematic review and meta-analysis of individual participant data.

Jennifer M Ross, Anani Badje, Molebogeng X Rangaka, A Sarah Walker, Adrienne E Shapiro, Katherine K Thomas, Xavier Anglaret, Serge Eholie, Delphine Gabillard, Andrew Boulle and 6 more

Open access · greenAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The lancet. HIV, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 5 pooled it
0.9field-weighted citation impact, top 14% 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, 5 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Household Contact Tracing With Intensified Tuberculosis and Human Immunodeficiency Virus Screening in South Africa: A Cluster-Randomized Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  13. Trial
  14. Article
  15. Observational
  16. Article
  17. Article
  18. Review
  19. Tuberculosis Preventive Treatment for Pregnant People With HIV in South Africa: A Modeling Analysis of Clinical Benefits and Risks.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    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

16 authors at 9 institutions in 5 countries.

Jennifer M RossDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA. Electronic address: jross3@uw.edu.
Anani BadjeUniversity of Bordeaux, Bordeaux, France.
Molebogeng X RangakaMRC Clinical Trials Unit, University College London, London, UK.
A Sarah WalkerMRC Clinical Trials Unit, University College London, London, UK.
Adrienne E ShapiroDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
Katherine K ThomasDepartment of Global Health, University of Washington, Seattle, WA, USA.
Xavier AnglaretUniversity of Bordeaux, Bordeaux, France.
Serge EholieUniversity Félix Houphouet-Boigny, Abidjan, Côte d'Ivoire.
Delphine GabillardUniversity of Bordeaux, Bordeaux, France.
Andrew BoulleWellcome Centre for Infectious Disease Research in Africa, University of Cape Town, Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
Gary MaartensWellcome Centre for Infectious Disease Research in Africa, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Robert J WilkinsonWellcome Centre for Infectious Disease Research in Africa, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK; Department of Infectious Diseases, Imperial College London, London, UK.
Nathan FordCentre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
Jonathan E GolubSchool of Medicine, Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA.
Brian G WilliamsSouth African Centre for Epidemiological Modelling and Analysis, Stellenbosch, South Africa.
Ruanne V BarnabasDepartment of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
University of Washington · USUniversité de Bordeaux · FRMRC Clinical Trials Unit at UCL · GBUniversity of Cape Town · ZAJohns Hopkins University · USStellenbosch University · ZAThe Francis Crick Institute · GBUniversité Félix Houphouët-Boigny · CIWellcome Centre for Infectious Diseases Research in Africa · ZA

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI EDWIN ROBERTO ORELLANA · 1988 to 2026
$104.9M
Validation and Application of a Model for Human-like TB Latency in RabbitsU19AI111276 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI ALLAND, DAVID, ALLAND, DAVID · 2014 to 2020
$23.3M
VENEREAL DISEASET32AI007140 · NIAID · UNIVERSITY OF WASHINGTON · PI Julia Cook Dombrowski · 1985 to 2026
$19.4M
Modeling approaches to prioritize TB prevention among people with HIV in UgandaK01AI138620 · NIAID · UNIVERSITY OF WASHINGTON · PI ROSS, JENNIFER M · 2019 to 2022
$446k
Cancer Research UK FC001218Medical Research Council MC_EX_G1100693Medical Research Council MC_EX_UU_G1100693Medical Research Council MC_UU_12023/22Medical Research Council MC_UU_12023/23Medical Research Council MC_UU_12023/26NIAID NIH HHS K01 AI138620NIAID NIH HHS L30 AI140333NIAID NIH HHS P30 AI027757NIAID NIH HHS T32 AI007140NIAID NIH HHS U19 AI111276Wellcome Trust 104803Wellcome Trust 203135Wellcome Trust 203135/Z/16/Z
6 · The paper itself

Abstract

backgroundIsoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups.

methodsWe searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400.

findingsOf 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49-0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43-1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR.

interpretationIsoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV.

fundingNational Institutes of Health and National Institute of Allergy and Infectious Diseases.

Indexed as

Antibiotic ProphylaxisAdultAnti-Retroviral AgentsAntitubercular AgentsCD4 Lymphocyte CountCoinfectionFemaleHIV InfectionsHumansIsoniazidMaleTreatment OutcomeTuberculosisAnti-Retroviral AgentsAntitubercular AgentsIsoniazid

Identifiers

PMID33387480
PMCPMC7875572
OpenAlexW3116072604

What OpenQuestion holds

Textmetadata
LicenceTDM
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.