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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

dc.contributor.authorObasa, Adetayo Emmanuelen_ZA
dc.contributor.authorAmbikan, Anoop T.en_ZA
dc.contributor.authorGupta, Sohamen_ZA
dc.contributor.authorNeogi, Ujjwalen_ZA
dc.contributor.authorJacobs, Graeme Brendonen_ZA
dc.date.accessioned2021-03-11T12:01:18Z
dc.date.available2021-03-11T12:01:18Z
dc.date.issued2019
dc.identifier.citationObasa, A. E., et al. 2021. 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. BMC Infectious Diseases, 21:214, doi:10.1186/s12879-021-05905-2
dc.identifier.issn1471-2334 (online)
dc.identifier.otherdoi:10.1186/s12879-021-05905-2
dc.identifier.urihttp://hdl.handle.net/10019.1/109641
dc.descriptionCITATION: Obasa, A. E., et al. 2021. 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. BMC Infectious Diseases, 21:214, doi:10.1186/s12879-021-05905-2.
dc.descriptionThe original publication is available at https://bmcinfectdis.biomedcentral.com
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractBackground: HIV-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. Methods: During 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. Results: Statistically 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. Conclusions: HTS-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.en_ZA
dc.description.urihttps://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05905-2
dc.format.extent8 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherBMC (part of Springer Nature)en_ZA
dc.subjectProtease inhibitorsen_ZA
dc.subjectDrug resistanceen_ZA
dc.subjectBoosted protease inhibitorsen_ZA
dc.subjectAntiviral nucleosidesen_ZA
dc.subjectHIV/AIDSen_ZA
dc.titleIncreased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africaen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyrighten_ZA


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