Evidence map›Paper›PMID 25140907›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2014

Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya.

Michael H Chung, Ingrid A Beck, Sandra Dross, Kenneth Tapia, James N Kiarie, Barbra A Richardson, Julie Overbaugh, Samah R Sakr, Grace C John-Stewart, Lisa M Frenkel

Abstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  18. HIV-1 drug resistance and resistance testing.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2016
    Review
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  20. Observational
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.

Michael H ChungDepartments of *Global Health; †Medicine; ‡Epidemiology, University of Washington, Seattle, WA; §Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA; ‖Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya; ¶Department of Biostatistics, University of Washington, Seattle, WA; #Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; **Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA; ††Coptic Hospital, Nairobi, Kenya; Departments of ‡‡Pediatrics; and §§Laboratory Medicine, University of Washington, Seattle, WA.
Ingrid A Beck
Sandra Dross
Kenneth Tapia
James N Kiarie
Barbra A Richardson
Julie Overbaugh
Samah R Sakr
Grace C John-Stewart
Lisa M Frenkel

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
Reservoirs of drug-resistant HIV-1R01AI058723 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2005 to 2009
$2.0M
Pediatric HIV-1 in Africa: Pathogenesis and ManagementK24HD054314 · NICHD · UNIVERSITY OF WASHINGTON · PI JOHN-STEWART, GRACE C. · 2006 to 2016
$1.2M
HAART Adherence Interventions in Africa: an RCTK23AI065222 · NIAID · UNIVERSITY OF WASHINGTON · PI CHUNG, MICHAEL HOONBAE · 2005 to 2009
$639k
NIAID NIH HHS K23 AI065222NIAID NIH HHS K23-AI065222NIAID NIH HHS P30 AI027757NIAID NIH HHS P30AI027757NIAID NIH HHS R01 AI058723NIAID NIH HHS R01-AI058723NICHD NIH HHS K24 HD054314PHS HHS U62/CCU024512
6 · The paper itself

Abstract

backgroundTransmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the time of ART initiation.

methodsPre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1000 copies/mL) at 6-month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing.

resultsAmong 386 participants, TDR was detected by OLA in 3.89% (95% confidence interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P < 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared with frequencies ≥2% (22% vs. 63%; P < 0.001).

conclusionsDetection of TDR by a point mutation assay may prevent the use of suboptimal ART.

Indexed as

Antiretroviral Therapy, Highly ActiveDrug Resistance, ViralAdultAnti-HIV AgentsDNA, ViralFemaleHIV-1HIV InfectionsHumansKenyaLigase Chain ReactionMaleMiddle AgedMolecular Diagnostic TechniquesMutationOligonucleotide ProbesAnti-HIV AgentsDNA, ViralOligonucleotide ProbesReverse Transcriptase Inhibitors

Identifiers

PMID25140907
PMCPMC4197120

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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.