Evidence map›Paper›PMID 30759103›Full record

ArticlePloS one2019

Presence, persistence and effects of pre-treatment HIV-1 drug resistance variants detected using next generation sequencing: A Retrospective longitudinal study from rural coastal Kenya.

Amin S Hassan, David F Bibby, Shalton M Mwaringa, Clara A Agutu, Kennedy K Ndirangu, Eduard J Sanders, Patricia A Cane, Jean L Mbisa, James A Berkley

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 3 pooled it
2.0field-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

10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 20 citations in OpenAlex.

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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

9 authors at 3 institutions in 2 countries.

Amin S HassanKEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.ORCID 0000-0001-5296-4264
David F BibbyVirus Reference Department, Public Health England, London, United Kingdom.
Shalton M MwaringaKEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.
Clara A AgutuKEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.
Kennedy K NdiranguKilifi County Hospital, Kilifi, Kenya.
Eduard J SandersKEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.
Patricia A CaneVirus Reference Department, Public Health England, London, United Kingdom.
Jean L MbisaVirus Reference Department, Public Health England, London, United Kingdom.
James A BerkleyKEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.ORCID 0000-0002-1236-849X
Kenya Medical Research Institute · KEPublic Health England · GBMoving the GoalPosts · KE

Funding

Wellcome Trust 107752/Z/15/ZWellcome Trust 209294/Z/17/ZWellcome Trust WT083579MAWellcome Trust WT089351MA
6 · The paper itself

Abstract

backgroundThe epidemiology of HIV-1 drug resistance (HIVDR) determined by Sanger capillary sequencing, has been widely studied. However, much less is known about HIVDR detected using next generation sequencing (NGS) methods. We aimed to determine the presence, persistence and effect of pre-treatment HIVDR variants detected using NGS in HIV-1 infected antiretroviral treatment (ART) naïve participants from rural Coastal Kenya.

methodsIn a retrospective longitudinal study, samples from HIV-1 infected participants collected prior [n = 2 time-points] and after [n = 1 time-point] ART initiation were considered. An ultra-deep amplicon-based NGS assay, calling for nucleotide variants at >2.0% frequency of viral population, was used. Suspected virologic failure (sVF) was defined as a one-off HIV-1 viral load of >1000 copies/ml whilst on ART.

resultsOf the 50 eligible participants, 12 (24.0% [95% CI: 13.1-38.2]) had at least one detectable pre-treatment HIVDR variant against Protease Inhibitors (PIs, n = 6 [12%]), Nucleoside Reverse Transcriptase Inhibitors (NRTIs, n = 4 [8.0%]) and Non-NRTIs (n = 3 [6.0%]). Overall, 15 pre-treatment resistance variants were detected (frequency, range: 2.3-92.0%). A positive correlation was observed between mutation frequency and absolute load for NRTI and/or NNRTI variants (r = 0.761 [p = 0.028]), but not for PI variants (r = -0.117 [p = 0.803]). Participants with pre-treatment NRTI and/or NNRTI resistance had increased odds of sVF (OR = 6.0; 95% CI = 1.0-36.9; p = 0.054).

conclusionsUsing NGS, pre-treatment resistance variants were common, though observed PI variants were unlikely transmitted, but rather probably generated de novo. Even when detected from a low frequency, pre-treatment NRTI and/or NNRTI resistance variants may adversely affect treatment outcomes.

Indexed as

Antiretroviral Therapy, Highly ActiveDrug Resistance, ViralAdultAnti-Retroviral AgentsFemaleGenetic VariationHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansKenyaLongitudinal StudiesMalePhylogenyRetrospective StudiesRural PopulationAnti-Retroviral Agents

Identifiers

PMID30759103
PMCPMC6373901
OpenAlexW2914383177

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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.