• Dorcas Maruapula, Kaelo K Seatla, Olorato Morerinyane, Kesaobaka Molebatsi, Jennifer Giandhari, Tulio de Oliveira, Rosemary M Musonda, Melvin Leteane, Sununguko W Mpoloka, Christopher F Rowley, Sikhulile Moyo, and Simani Gaseitsiwe.
• Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
• Medicine (Baltimore). 2022 Jul 15; 101 (28): e29577e29577.

BackgroundIndividuals 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-naïve HIV-positive individuals in Botswana.MethodsWe evaluated the prevalence of low-frequency DRMs among cART-naïve individuals previously sequenced using Sanger sequencing. The generated pol amplicons were sequenced by next-generation sequencing.ResultsWe 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).ConclusionNext-generation sequencing was able to detect low-frequency DRMs in this cohort in Botswana, but these DRMs did not contribute significantly to VF.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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