Drug resistance mutations against protease, reverse transcriptase and integrase inhibitors in people living with HIV-1 receiving boosted protease inhibitors in South Africa
Date
2020-03
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Abstract
The South African national combination antiretroviral therapy (cART) roll-out program
started in 2006, with over 4.4 million people accessing treatment since it was first
introduced. HIV-1 drug resistance can hamper the success of cART. This study
determined the patterns of HIV-1 drug-resistance associated mutations (RAMs) in
People Living with HIV-1 (PLHIV-1). Receiving first (for children below 3 years of age)
and second-line (for adults) cART regimens in South Africa. During 2017 and 2018,
110 patients plasma samples were selected, 96 samples including those of 17 children
and infants were successfully analyzed. All patients were receiving a boosted protease
inhibitor (bPI) as part of their cART regimen. The viral sequences were analyzed for
RAMs through genotypic resistance testing. We performed genotypic resistance testing
(GRT) for Protease inhibitors (PIs), Reverse transcriptase inhibitors (RTIs) and Integrase
strand transfer inhibitors (InSTIs). Viral sequences were subtyped using REGAv3 and
COMET. Based on the PR/RT sequences, HIV-1 subtypes were classified as 95 (99%)
HIV-1 subtype C (HIV-1C) while one sample as 02_AG. Integrase sequencing was
successful for 89 sequences, and all the sequences were classified as HIV-1C (99%,
88/89) except one sequence classified CRF02_AG, as observed in PR/RT. Of the
96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM
nucleoside reverse transcriptase inhibitor (NRTI). The most frequent non-nucleoside
reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). Protease
inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed.
Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations while one sample had T66I. The accessory RAM E157Q was identified in two (2.2%).
The data indicates that the majority of the patients failed on bPIs didn’t have any
mutation; therefore adherence could be major issue in these groups of individuals. We
propose continued viral load monitoring for better management of infected PLHIV.
Description
CITATION: Obasa, A.E., Mikasi, S.G., Brado, D., Cloete, R., Singh, K., Neogi, U. & Jacobs, G.B. 2020. Drug resistance mutations against protease, reverse transcriptase and integrase inhibitors in people living with HIV-1 receiving boosted protease inhibitors in South Africa. Frontier in Microbiology, 11:438:1-9. https://doi.org/10.3389/fmicb.2020.00438.
The original publication is available at https://www.frontiersin.org/journals/microbiology#
The original publication is available at https://www.frontiersin.org/journals/microbiology#
Keywords
HIV-1, reverse transcriptase inhibitor (RTI), protease inhibitor (PI), integrase strand-transfer inhibitor (InSTI), resistance, South Africa, resistance-associated mutations (RAMs), combination antiretroviral therapy (cART)
Citation
Obasa AE, Mikasi SG, Brado D, Cloete R, Singh K, Neogi U and Jacobs GB (2020) Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa. Front. Microbiol. 11:438. doi: 10.3389/fmicb.2020.00438
Obasa, A.E., Mikasi, S.G., Brado, D., Cloete, R., Singh, K., Neogi, U. & Jacobs, G.B. 2020. Drug resistance mutations against protease, reverse transcriptase and integrase inhibitors in people living with HIV-1 receiving boosted protease inhibitors in South Africa. Frontier in Microbiology, 11:438:1-9. https://doi.org/10.3389/fmicb.2020.00438.
Obasa, A.E., Mikasi, S.G., Brado, D., Cloete, R., Singh, K., Neogi, U. & Jacobs, G.B. 2020. Drug resistance mutations against protease, reverse transcriptase and integrase inhibitors in people living with HIV-1 receiving boosted protease inhibitors in South Africa. Frontier in Microbiology, 11:438:1-9. https://doi.org/10.3389/fmicb.2020.00438.