Evidence map›Paper›PMID 22933296›Full record

ArticleJournal of virology2012

Ultrasensitive allele-specific PCR reveals rare preexisting drug-resistant variants and a large replicating virus population in macaques infected with a simian immunodeficiency virus containing human immunodeficiency virus reverse transcriptase.

Valerie F Boltz, Zandrea Ambrose, Mary F Kearney, Wei Shao, Vineet N Kewalramani, Frank Maldarelli, John W Mellors, John M Coffin

Open access · bronzeAbstract readValidation Study
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
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

18 citing papers in PubMed, 24 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

8 authors at 5 institutions in 1 country.

Valerie F BoltzHIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, USA. boltzv@mail.nih.gov
Zandrea Ambrose
Mary F Kearney
Wei Shao
Vineet N Kewalramani
Frank Maldarelli
John W Mellors
John M Coffin
National Cancer Institute · USUniversity of Pittsburgh · USFrederick National Laboratory for Cancer Research · USScience Applications International Corporation (United States) · USTufts University · US

Funding

New Animal Models to Study HIV-1 Pathogenesis, Therapy, and ReservoirsZIABC010488 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEWALRAMANI, VINEET N · 2009 to 2025
$5.2M
Origin and Evolution of HIV-1 Drug Resistance in the RT-SHIVmne Macaque ModelR01AI080290 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSE, ZANDREA · 2010 to 2013
$1.5M
Intramural NIH HHSNIAID NIH HHS R01 AI080290
6 · The paper itself

Abstract

It has been proposed that most drug-resistant mutants, resulting from a single-nucleotide change, exist at low frequency in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) populations in vivo prior to the initiation of antiretroviral therapy (ART). To test this hypothesis and to investigate the emergence of resistant mutants with drug selection, we developed a new ultrasensitive allele-specific PCR (UsASP) assay, which can detect drug resistance mutations at a frequency of ≥0.001% of the virus population. We applied this assay to plasma samples obtained from macaques infected with an SIV variant containing HIV-1 reverse transcriptase (RT) (RT-simian-human immunodeficiency [SHIV](mne)), before and after they were exposed to a short course of efavirenz (EFV) monotherapy. We detected RT inhibitor (RTI) resistance mutations K65R and M184I but not K103N in 2 of 2 RT-SHIV-infected macaques prior to EFV exposure. After three doses over 4 days of EFV monotherapy, 103N mutations (AAC and AAT) rapidly emerged and increased in the population to levels of ∼20%, indicating that they were present prior to EFV exposure. The rapid increase of 103N mutations from <0.001% to 20% of the viral population indicates that the replicating virus population size in RT-SHIV-infected macaques must be 10(6) or more infected cells per replication cycle.

Indexed as

Macaca nemestrinaAlkynesAllelesAnimalsBenzoxazinesCyclopropanesDrug Resistance, ViralHIV Reverse TranscriptaseMutationPolymerase Chain ReactionSequence Analysis, DNASimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusAlkynesBenzoxazinesCyclopropanesefavirenzHIV Reverse Transcriptasereverse transcriptase, Human immunodeficiency virus 1

Identifiers

PMID22933296
PMCPMC3497681
OpenAlexW2104559550

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.