Evidence map›Paper›PMID 27914856›Full record

ArticleThe Lancet. Infectious diseases2017

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study.

John Gregson, Pontiano Kaleebu, Vincent C Marconi, Cloete van Vuuren, Nicaise Ndembi, Raph L Hamers, Phyllis Kanki, Christopher J Hoffmann, Shahin Lockman, Deenan Pillay and 9 more

Open access · hybridAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 3 pooled it
6.0field-weighted citation impact, top 3% 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

47 citing papers in PubMed, 3 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 18 institutions in 7 countries.

John GregsonDepartment of Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Pontiano KaleebuMRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; Uganda Research Unit on AIDS, Entebbe, Uganda.
Vincent C MarconiDepartment of Global Health, Emory University Rollins School of Public Health, Emory University, Atlanta, GA, USA; Division of Infectious Diseases, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
Cloete van VuurenDivision of Infectious Diseases, University of the Free State, and 3 Military Hospital, Bloemfontein, South Africa.
Nicaise NdembiInstitute of Human Virology Nigeria, Abuja, Nigeria.
Raph L HamersAmsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center, University of Amsterdam, Netherlands.
Phyllis KankiDepartment of Immunology and Infectious Disease, Harvard T H Chan School of Public Health, Boston, MA, USA.
Christopher J HoffmannAurum Institute, Johannesburg South Africa; Johns Hopkins University, Baltimore, MD, USA.
Shahin LockmanBrigham and Women's Hospital, Boston, MA, USA.
Deenan PillayDepartment of Infection, University College London, London, UK; Africa Health Research Institute, KwaZulu Natal, South Africa.
Tulio de OliveiraNelson R Mandela School of Medicine, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
Nathan ClumeckSaint-Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Gillian HuntNational Institute for Communicable Diseases, Sandringham, South Africa.
Bernhard KerschbergerMédecins Sans Frontières (Operational Centre Geneva), Mbabane, Swaziland.
Robert W ShaferDepartment of Medicine, Stanford University, Stanford, CA, USA.
Chunfu YangInternational Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Elliot RaizesDivision of Global HIV/AIDS, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Rami KantorDivision of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA.
Ravindra K GuptaDepartment of Infection, University College London, London, UK; Africa Health Research Institute, KwaZulu Natal, South Africa. Electronic address: ravindra.gupta@ucl.ac.uk.
Centers for Disease Control and Prevention · USAcademic Medical Center · NLAfrica Health Research Institute · ZABrigham and Women's Hospital · USBrown University · USEmory University · USHarvard University · USInstitute of Human Virology · NGJohns Hopkins University · USLondon School of Hygiene & Tropical Medicine · GBMédecins Sans Frontières · UGNational Institute for Communicable DiseasesStanford University · USUganda Virus Research Institute · UGUniversité Libre de Bruxelles · BEUniversity College London · GBUniversity of KwaZulu-Natal · ZAUniversity of the Free State · ZA

Funding

Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI CURT G BECKWITH · 1998 to 2026
$51.7M
Botswana-Harvard T.H. Chan School of Public Health AIDS Initiative Partnership CTU Y18 SupplementUM1AI069456 · NIAID · THE BOTSWANA HARVARD HEALTH PARTNERSHIP · PI SHAHIN LOCKMAN, Joseph Moeketsi Makhema · 2012 to 2026
$29.4M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025008 · NCRR · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2007 to 2011
$29.0M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
PUBLIC HIV DRUG RESISTANCE DATABASER01AI068581 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 2006 to 2017
$6.2M
HIV-1 Drug Resistance in Different SubtypesR01AI066922 · NIAID · STANFORD UNIVERSITY · PI KANTOR, RAMI, KATZENSTEIN, DAVID ALLENBERG · 2008 to 2012
$3.6M
Optimizing HIV Treatment Monitoring under Resource ConstraintsR01AI108441 · NIAID · BROWN UNIVERSITY · PI HOGAN, JOSEPH W, KANTOR, RAMI · 2015 to 2019
$3.5M
Antiretroviral drug resistance in KwaZulu NatalR01AI098558 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI KURITZKES, DANIEL R., MARCONI, VINCENT CHARLES · 2013 to 2017
$2.3M
CGH CDC HHS U2G GH000925Medical Research Council G0600044Medical Research Council MC_U950080938NCATS NIH HHS UL1 TR000454NCRR NIH HHS UL1 RR025008NIAID NIH HHS P30 AI042853NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI066922NIAID NIH HHS R01 AI068581NIAID NIH HHS R01 AI098558NIAID NIH HHS R01 AI108441NIAID NIH HHS UM1 AI069456Wellcome Trust
6 · The paper itself

Abstract

backgroundHIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.

methodsWe retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.

findingsOf 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60·5 cells per μL [IQR 21·0-128·0] in patients with TAMS vs 95·0 cells per μL [37·0-177·0] in patients without TAMs; p=0·007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0·0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0·0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0·0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0·64 (p<0·0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1·29 (1·13-1·47; p<0·0001)

interpretationTAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.

fundingThe Wellcome Trust.

Indexed as

AdultAfrica South of the SaharaAlkynesAntiretroviral Therapy, Highly ActiveBenzoxazinesCyclopropanesDrug Resistance, ViralFemaleHIV-1HIV InfectionsHumansLamivudineMaleMutationNevirapineRetrospective StudiesAlkynesBenzoxazinesCyclopropanesefavirenzLamivudineNevirapineReverse Transcriptase InhibitorsTenofovir

Identifiers

PMID27914856
PMCPMC5421555
OpenAlexW2557523555

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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.