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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Date
2020
Authors
Mabeya, Sepha
Nyamache, Anthony
Ngugi, Caroline
Nyerere, Andrew
Lihana, Raphael
Journal Title
Journal ISSN
Volume Title
Publisher
Jimma University
Abstract
BACKGROUND: Antiretroviral therapy containing an integrase strand transfer inhibitor plus two Nucleoside Reverse Transcriptase inhibitors has now been recommended for treatment of HIV-1-infected patients. This thus determined possible pre-existing integrase resistance associated mutations in the integrase gene prior to introduction of integrase inhibitors combination therapy in Kenya.
METHODS: Drug experienced HIV patients were enrolled at Kisii Teaching and Referral in Kenya. Blood specimens from (33) patients were collected for direct sequencing of HIV-1 polintegrase genes. Drug resistance mutations were interpreted according to the Stanford algorithm and phylogenetically analysed using insilico tools.
RESULTS: From pooled 188 Kenyan HIV integrase sequences that were analysed for drug resistance, no major mutations conferring resistance to integrase inhibitors were detected. However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). Phylogenetic analysis (330 sequences revealed that HIV-1 subtype A1 accounted for majority of the infections, 26 (78.8%), followed by D, 5 (15.2%) and C, 2 (6%).
CONCLUSION: The integrase inhibitors will be effective in Kenya where HIV-1 subtype A1 is still the most predominant. However, occurring polymorphisms may warrant further investigation among drug experienced individuals on dolutegravir combination or integrase inhibitor treatment.
Description
A research article published in Ethiopian Journal of Health Sciences
Keywords
Integrase, Dolutegravir, Mutations, Resistance
Citation
Sepha, M., Anthony, N., Caroline, N., Andrew, N., & Raphael, L. (2020). 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. Ethiopian journal of health sciences, 30(1).