Prevalence of the K65R mutation in subtype C HIV-1-infected subjects failing TDF-containing first-line antiretroviral therapy in South Africa using deep sequencing

• Published in: Antiviral therapy 2014-01, Vol.19, p.A76-A76
• Main Authors: Casadella, M, Noguera-Julian, M, Sunpath, H, Gordon, M, Kuritzkes, D R, Marconi, V, Paredes, R
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus 1
• ISSN: 1359-6535

Tenofovir (TDF) is one of the first-line nucleoside reverse transcriptase inhibitors antiretroviral therapy options in the South African national treatment plan. In a previous study, 69.7% of participants developing virological failure (VF) to a TDF-containing regimen in South Africa had the K65R mutation by Sanger sequencing of plasma viruses. We performed a proof-of-concept analysis in South African subjects infected with Subtype C HIV-1 who developed VF to TDF and did not have the K65R mutation at VF by Sanger sequencing. The complete pol gene was amplified and sequenced in a MiSeq platform using a Nextera-XT shotgun approach. A 1% threshold level was chosen for detection of minority variants. Resistance mutations were defined according to the IAS-USA 2013 list. Deep HIV-1 sequencing slightly increases the prevalence of K65R mutation at TDF failure, but enables detection of additional, clinically relevant, mutations in a large proportion of subjects. With adequate logistics and further cost reductions, it could become a cost-effective tool for resistance surveillance and clinical monitoring in resource-limited settings.