Evidence map›Paper›PMID 30977467›Full record

ArticleAntiviral therapy2019

Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia.

F Parker Hudson, Lloyd Mulenga, Andrew O Westfall, Ranjit Warrier, Aggrey Mweemba, Michael S Saag, Jeffrey Sa Stringer, Joseph J Eron, Benjamin H Chi

Abstract read
In one paragraph

Article in Antiviral therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

9 authors.

F Parker HudsonDepartment of Internal Medicine, University of Texas at Austin, Austin, TX, USA.
Lloyd MulengaSchool of Medicine, University of Zambia, Lusaka, Zambia.
Andrew O WestfallDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Ranjit WarrierCentre for Infectious Disease Research in Zambia, Lusaka, Zambia.
Aggrey MweembaSchool of Medicine, University of Zambia, Lusaka, Zambia.
Michael S SaagDepartment of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Jeffrey Sa StringerUNC Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joseph J EronDepartment of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Benjamin H ChiUNC Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Funding

Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Alabama-Clinical Trials UnitU01AI069452 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SAAG, MICHAEL S. · 2007 to 2011
$16.6M
Training in Sexually Transmitted Infections and HIVT32AI007001 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SENA-SOBERANO, ARLENE C. · 1985 to 2025
$10.9M
Mentoring new investigators in PMTCT implementation researchK24AI120796 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Benjamin H. Chi · 2016 to 2026
$1.3M
NIAID NIH HHS K24 AI120796NIAID NIH HHS P30 AI027767NIAID NIH HHS P30 AI050410NIAID NIH HHS T32 AI007001NIAID NIH HHS U01 AI069452
6 · The paper itself

Abstract

backgroundHIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia.

methodsWe analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death.

resultsOf 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%.

conclusionsWe found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.

Indexed as

Drug Resistance, ViralAdultAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountFemaleGenotypeHIV-1HIV InfectionsHumansMaleMiddle AgedMutationRNA, ViralTreatment FailureViral LoadAnti-HIV AgentsRNA, Viral

Identifiers

PMID30977467
PMCPMC9119376

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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.