Title: Low-frequency HIV-1 drug resistance mutations in antiretroviral naive individuals in Botswana
Authors: Maruapula D, Seatla KK, Morerinyane O, Molebatsi K, Giandhari J, de Oliveira T, Musonda RM, Leteane M, Mpoloka SW, Rowley CF, Moyo S, Gaseitsiwe S.
Journal: Medicine (Baltimore),101(28):e29577. doi: 10.1097/MD.0000000000029577: (2022)
Background: Individuals living with human immunodeficiency virus (HIV) who experience virological failure (VF) after combination antiretroviral therapy (cART) initiation may have had low-frequency drug resistance mutations (DRMs) at cART initiation. There are no data on low-frequency DRMs among cART-na├»ve HIV-positive individuals in Botswana.
Methods: We evaluated the prevalence of low-frequency DRMs among cART-na├»ve individuals previously sequenced using Sanger sequencing. The generated pol amplicons were sequenced by next-generation sequencing.
Results: We observed low-frequency DRMs (detected at <20% in 33/103 (32%) of the successfully sequenced individuals, of whom four also had mutations detected at >20%. K65R was the most common low-frequency DRM detected in 8 individuals. Eighty-two of the 103 individuals had follow-up viral load data while on cART. Twenty-seven of the 82 individuals harbored low-frequency DRMs. Only 12 of 82 individuals experienced VF. The following low-frequency DRMs were observed in four individuals experiencing VF: K65R, K103N, V108I, and Y188C. No statistically significant difference was observed in the prevalence of low-frequency DRMs between individuals experiencing VF (4/12) and those not experiencing VF (23/70) (P = .97). However, individuals with non-nucleoside reverse transcriptase inhibitors-associated low-frequency DRMs were 2.68 times more likely to experience VF (odds ratio, 2.68, 95% confidential interval, 0.4-13.9) compared with those without (P = .22).
Conclusion: Next-generation sequencing was able to detect low-frequency DRMs in this cohort in Botswana, but these DRMs did not contribute significantly to VF.
Citation: Maruapula D, Seatla KK, Morerinyane O, Molebatsi K, Giandhari J, de Oliveira T, Musonda RM, Leteane M, Mpoloka SW, Rowley CF, Moyo S, Gaseitsiwe S. Low-frequency HIV-1 drug resistance mutations in antiretroviral naive individuals in Botswana Medicine (Baltimore),101(28):e29577. doi: 10.1097/MD.0000000000029577: (2022).
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