Evidence map›Paper›PMID 29661652›Full record

ArticleJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology2018

Next generation sequencing reveals a high frequency of CXCR4 utilizing viruses in HIV-1 chronically infected drug experienced individuals in South Africa.

Nontokozo D Matume, Denis M Tebit, Laurie R Gray, Marie-Louise Hammarskjold, David Rekosh, Pascal O Bessong

Abstract read
In one paragraph

Article in Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Article
  4. 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

6 authors.

Nontokozo D MatumeHIV/AIDS & Global Health Research Programme, University of Venda, Thohoyandou, South Africa. Electronic address: 11575283@mvula.univen.ac.za.
Denis M TebitMyles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA. Electronic address: dmt6u@eservices.virginia.edu.
Laurie R GrayMyles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA. Electronic address: lrg4n@virginia.edu.
Marie-Louise HammarskjoldMyles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA. Electronic address: mh7g@virginia.edu.
David RekoshMyles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, USA. Electronic address: dr4u@virginia.edu.
Pascal O BessongHIV/AIDS & Global Health Research Programme, University of Venda, Thohoyandou, South Africa. Electronic address: bessong@univen.ac.za.

Funding

Global Infectious Disease Research Training Program at UVAD43TW006578 · FIC · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUERRANT, RICHARD L · 2003 to 2018
$2.7M
FIC NIH HHS D43 TW006578
6 · The paper itself

Abstract

backgroundEntry inhibitors, such as Maraviroc, bind to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses). In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. The use of Maraviroc is reserved for salvage therapy in South Africa.

objectiveIn this study, we examined the frequency of R5 and X4 viruses, using next generation sequencing, in patients under treatment to draw inferences on the utility of Maraviroc in a South African population. STUDY

designProviral DNA was isolated from peripheral blood mononuclear cells (PBMC) of 72 chronically HIV infected patients on antiretroviral treatment. HIV V3 loop gene was amplified and sequenced on an Illumina MiniSeq platform. Viral subtypes were determined by the jumping profile Hidden Markov Model (jpHMM) and REGA genotyping tools. De Novo consensus sequences were derived for the majority and minority populations for each patient using Geneious

resultsQuality V3 loop sequences were obtained from 72 patients, with 5 years (range: 0-16) median duration on treatment. Subtypes A1, B and C viruses were identified at frequencies of 4% (3/72), 4% (3/72) and 92% (66/72) respectively. Fifty four percent (39/72) of patients exclusively harboured R5 viral quasispecies; and 21% (15/72) exclusively harbored X4 viral quasispecies. Twenty five percent of patients (18/72) harbored dual/mixture of R5X4 quasispecies. Of these 18 patients, about 28% (5/18) harbored the R5+X4, a mixture with a majority R5 and minority X4 viruses, while about 72% (13/18) harbored the R5X4+ mixture with a majority X4 and minority R5 viruses. The proportion of all patients who harbored X4 viruses either exclusively or dual/mixture was 46% (33/72). Thirty-five percent (23/66) of the patients who were of HIV-1 subtype C harboured X4 viruses (χ

conclusionThe effectiveness of Maraviroc as a component in salvage therapy may be compromised for a significant number of chronically infected patients harboring CXCR4 utilizing viruses.

Indexed as

GenotypeHigh-Throughput Nucleotide SequencingViral TropismAdolescentAdultAgedAnti-Retroviral AgentsChildChild, PreschoolFemaleGenotyping TechniquesHIV-1HIV InfectionsHumansLeukocytes, MononuclearMaleAnti-Retroviral AgentsCXCR4 protein, humanMaravirocReceptors, CXCR4Receptors, HIVChronic HIV infectionCo-receptor usageMaravirocNext generation sequencingSouth Africa

Identifiers

PMID29661652
PMCPMC7229640

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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.