Evidence map›Paper›PMID 26175454›Full record

ArticleThe Journal of infectious diseases2016

Phenotype, Genotype, and Drug Resistance in Subtype C HIV-1 Infection.

Anne Derache, Carole L Wallis, Saran Vardhanabhuti, John Bartlett, Nagalingeswaran Kumarasamy, David Katzenstein

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–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

9 citing papers in PubMed.

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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

6 authors.

Anne DeracheDivision of Infectious Diseases, Stanford University, California.
Carole L WallisDepartment of Molecular Pathology, Lancet Laboratories and BARC-SA, Johannesburg, South Africa.
Saran VardhanabhutiHarvard School of Public Health, Boston, Massachusetts.
John BartlettDuke University Medical Center, Durham, North Carolina.
Nagalingeswaran KumarasamyY. R. Gaitonde Centre for AIDS Research and Education, Chennai, India.
David KatzensteinDivision of Infectious Diseases, Stanford University, California.

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
WOMEN'S HEALTH AGENDAU01AI038858 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI BENSON, CONSTANCE ANN · 1996 to 2008
$157.5M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
The Malawi Clinical Trials UnitU01AI069518 · NIAID · JOHNS HOPKINS UNIVERSITY · PI TAHA, TAHA E · 2007 to 2011
$46.7M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitU01AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BENSON, CONSTANCE ANN · 2007 to 2011
$19.3M
HIV-1 Drug Resistance in Different SubtypesR01AI066922 · NIAID · STANFORD UNIVERSITY · PI KANTOR, RAMI, KATZENSTEIN, DAVID ALLENBERG · 2008 to 2012
$3.6M
NIAID NIH HHS AI068634NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI066922NIAID NIH HHS R01 AI066922-01A2NIAID NIH HHS U01 AI038858NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01AI068636NIAID NIH HHS U01 AI069432NIAID NIH HHS U01AI069432NIAID NIH HHS U01 AI069518NIAID NIH HHS U01AI069518NIAID NIH HHS U01AI38858NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636PHS HHS U01069484
6 · The paper itself

Abstract

backgroundVirologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure.

methodsAIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations.

resultsGenotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI.

conclusionsAlthough genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype.

Indexed as

AdultAfrica South of the SaharaAnti-HIV AgentsDrug Resistance, ViralFemaleGenotypeHIV-1HIV InfectionsHumansMaleMutagenesis, Site-DirectedPhenotypeThailandAnti-HIV Agents2nd NNRTI generationfirst-line failuregenotype/phenotype comparisonHIVsubtype C

Identifiers

PMID26175454
PMCPMC4690149

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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.