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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Deep sequencing reveals minor protease resistance mutations in Patients failing a protease inhibitor regimen
Journal of Virology, Volume 86, No. 11, Year 2012
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Description
Standard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise< 20% of the circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an antiretroviral regimen after antiretroviral failure. In patients with poor adherence, resistant variants may not reach this threshold. Therefore, deep sequencing would be potentially valuable for detecting minority resistant variants. We compared bulk sequencing and deep sequencing to detect HIV-1 drug resistance at the time of a second-line protease inhibitor (PI)-based antiretroviral regimen failure. Eligibility criteria were virologic failure (HIV-1 RNA load of>500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance. © 2012, American Society for Microbiology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3372173/bin/supp_86_11_6231__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3372173/bin/supp_86.11.6231_TableS1.pdf
Authors & Co-Authors
Fisher, Randall G.
South Africa, Stellenbosch
Stellenbosch University
Van Zyl, Gert Uves
South Africa, Stellenbosch
Stellenbosch University
South Africa, Johannesburg
National Health Laboratory Service
Travers, Simon A.A.
South Africa, Bellville
University of the Western Cape
Pond, Sergei L.Kosakovsky
United States, La Jolla
University of California, San Diego
Engelbrech, Susan
South Africa, Stellenbosch
Stellenbosch University
South Africa, Johannesburg
National Health Laboratory Service
Murrell, Ben
South Africa, Stellenbosch
Stellenbosch University
South Africa, Tygerberg
South African Medical Research Council
Scheffler, Konrad
South Africa, Stellenbosch
Stellenbosch University
Smith, Davey
United States, La Jolla
University of California, San Diego
Statistics
Citations: 60
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1128/JVI.06541-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Cancer
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study