biostudies-literatureBurdorf RMNational Institute of Allergy and Infectious DiseasesUNC Lineberger Comprehensive Cancer CenterNIAID NIH HHSNCI NIH HHSNational Institutes of HealthNIH HHS86-94https://www.ebi.ac.uk/biostudies/studies/S-EPMC11272071biostudies-literatureUnknown230(1)<h4>Background</h4>The 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.<h4>Methods</h4>We 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%.<h4>Results</h4>We 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.<h4>Conclusions</h4>Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.The Journal of infectious diseasesImpact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes.PMC11272071R01-HD080485P30 AI050410R01 AI140970P30 CA016086R01-AI40970P30-AI050410P30-CA016086Maliwichi MSwanstrom RChagomerana MBJumbe AZhou SWallie SLong NAmon CLi YAdams LBurdorf RMTegha GHosseinipour MCHill CSfalseImpact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes.<h4>Background</h4>The 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.<h4>Methods</h4>We 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%.<h4>Results</h4>We 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.<h4>Conclusions</h4>Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.2024-01-01T00:00:00Z2024 Jul2025-04-04T02:21:54.981Z2025-04-04T02:21:54.981ZS-EPMC112720713905273310.1093/infdis/jiae131