Evidence map›Paper›PMID 33632139›Full record

ArticleBMC infectious diseases2021

Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa.

Adetayo Emmanuel Obasa, Anoop T Ambikan, Soham Gupta, Ujjwal Neogi, Graeme Brendon Jacobs

Open access · goldAbstract read
In one paragraph

Article in BMC infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 33% 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, 1 synthesis or guideline pooled it, 13 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

5 authors at 2 institutions in 2 countries.

Adetayo Emmanuel ObasaDepartment of Pathology, Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, 7505, South Africa. obasa@sun.ac.za.ORCID http://orcid.org/0000-0003-0934-9586
Anoop T AmbikanDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.
Soham GuptaDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.
Ujjwal NeogiDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.
Graeme Brendon JacobsDepartment of Pathology, Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, 7505, South Africa.
Karolinska Institutet · SEStellenbosch University · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients on the South African national second-line cART regimen receiving bPIs.

methodsDuring 2017 and 2018, 67 patient samples were sequenced using high-throughput sequencing (HTS), of which 56 samples were included in the final analysis because the patient's treatment regimen was available at the time of sampling. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.

resultsStatistically significantly higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p = 0.042) and integrase inhibitor RAM (4%; 2/56; p = 0.002). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase.

conclusionsHTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in < 20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.

Indexed as

Anti-Retroviral AgentsDrug Resistance, ViralGenes, polGenotypeHIV-1HIV InfectionsHIV Protease InhibitorsHumansMutationQuasispeciesRNA, ViralSouth AfricaAnti-Retroviral AgentsHIV Protease InhibitorsRNA, ViralBoosted protease inhibitors (bPIs)High-throughput sequencing (HTS)Non-nucleoside reverse transcriptase inhibitors (NNRTIs)Nucleoside reverse transcriptase inhibitors (NRTIs)

Identifiers

PMID33632139
PMCPMC7908688
OpenAlexW3117110387

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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.