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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency
Scientific Reports, Volume 6, Article 38153, Year 2016
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Description
The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort. Ten-fold variation in susceptibility to PIs atazanavir and lopinavir was observed across 20 viruses, with EC50 s ranging 0.71-6.95 nM for atazanvir and 0.64-8.54 nM for lopinavir. Ten amino acid residues in Gag correlated with lopinavir EC50 (p < 0.01), of which 380 K and 389I showed modest impacts on in vitro drug susceptibility. Finally a significant relationship between drug susceptibility and replication capacity was observed for atazanavir and lopinavir but not darunavir. Our findings demonstrate large variation in susceptibility of PI-naïve subtype C viruses that appears to correlate with replication efficiency and could impact clinical outcomes. © 2016 The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC5128871/bin/srep38153-s1.docx
Authors & Co-Authors
Sutherland, Katherine A.
United Kingdom, London
Ucl Faculty of Medical Sciences
Collier, Dami Aderonke
United States, Atlanta
Emory University
Claiborne, Daniel T.
United States, Atlanta
Emory University
Prince, Jessica L.
United States, Atlanta
Emory University
Deymier, Martin J.
United States, Atlanta
Emory University
Goldstein, Richard A.
United States, Atlanta
Emory University
Hunter, Eric
United States, Atlanta
Emory University
Gupta, Ravindra K.
United States, Atlanta
Emory University
Statistics
Citations: 9
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.1038/srep38153
ISSN:
20452322
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Study Locations
Zambia