Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya
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Abstract
BACKGROUND: Antiretroviral therapy containing an integrasestrand transfer inhibitor plus two Nucleoside ReverseTranscriptase inhibitors has now been recommended fortreatment of HIV-1-infected patients. This thus determinedpossible pre-existing integrase resistance-associated mutations inthe integrase gene prior to introduction of integrase inhibitorscombination therapy in Kenya.
METHODS: Drug experienced HIV patients were enrolled at KisiiTeaching and Referral in Kenya. Blood specimens from (33)patients were collected for direct sequencing of HIV-1 pol-integrase genes. Drug resistance mutations were interpretedaccording to the Stanford algorithm and phylogenetically analysedusing insilico tools.
RESULTS: From pooled 188 Kenyan HIV integrase sequences thatwere analysed for drug resistance, no major mutations conferringresistance to integrase inhibitors were detected. However,polymorphic accessory mutations associated with reducedsusceptibility of integrase inhibitors were observed in lowfrequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%),G140S/A/C (1.1%) and E157Q (0.5%). Phylogenetic analysis (330sequences revealed that HIV-1 subtype A1 accounted for majorityof the infections, 26 (78.8%), followed by D, 5 (15.2%) and C, 2(6%).
CONCLUSION: The integrase inhibitors will be effective in Kenyawhere HIV-1 subtype A1 is still the most predominant. However,occurring polymorphisms may warrant further investigationamong drug experienced individuals on dolutegravir combinationor integrase inhibitor treatment