ArticleThe Journal of infectious diseases2024
Impact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes.
Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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Authors and funding
14 authors.
Funding
Abstract
backgroundThe association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs.
methodsWe enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor-based regimen and cohort B started a protease inhibitor-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%.
resultsWe sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58-6.18) and 2.38 (95% CI, 1.00-5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART.
conclusionsUsing accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.
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