Original Research

Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy

Zhiyong Zhou, Kevin Tang, Guoqing Zhang, Nellie Wadonda-Kabondo, Kundai Moyo, Lori A. Rowe, Joshua R. DeVos, Nick Wagar, Du-Ping Zheng, Hongxiong Guo, John Nkengasong, Mike Frace, Scott Sammons, Chunfu Yang
African Journal of Laboratory Medicine | Vol 7, No 1 | a708 | DOI: https://doi.org/10.4102/ajlm.v7i1.708 | © 2018 Zhiyong Zhou, Kevin Tang, Guoqing Zhang, Nellie Wadonda-Kabondo, Kundai Moyo, Lori A. Rowe, Joshua R DeVos, Nick Wagar, Du-Ping Zheng, Hongxiong Guo, John Nkengasong, Mike Frace, Scott Sammons, Chunfu Yang | This work is licensed under CC Attribution 4.0
Submitted: 13 October 2017 | Published: 30 May 2018

About the author(s)

Zhiyong Zhou, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Kevin Tang, Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Guoqing Zhang, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Nellie Wadonda-Kabondo, Department of Preventive Health, Ministry of Health, Lilongwe, Malawi
Kundai Moyo, Department of Preventive Health, Ministry of Health, Lilongwe, Malawi
Lori A. Rowe, Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Joshua R. DeVos, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Nick Wagar, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Du-Ping Zheng, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Hongxiong Guo, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
John Nkengasong, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Mike Frace, Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Scott Sammons, Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, United States
Chunfu Yang, International Laboratory Branch, Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States


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Abstract

Background: Minority drug resistance mutations (DRMs) that are often missed by Sanger sequencing are clinically significant, as they can cause virologic failure in individuals treated with antiretroviral therapy (ART) drugs.

Objective: This study aimed to estimate the prevalence of minor DRMs among patients enrolled in a Malawi HIV drug resistance monitoring survey at baseline and at one year after initiation of ART.

Methods: Forty-one plasma specimens collected from HIV-1 subtype C-positive patients and seven clonal control samples were analysed using ultra-deep sequencing technology.

Results: Deep sequencing identified all 72 DRMs detected by Sanger sequencing at the level of ≥20% and 79 additional minority DRMs at the level of < 20% from the 41 Malawian clinical specimens. Overall, DRMs were detected in 85% of pre-ART and 90.5% of virologic failure patients by deep sequencing. Among pre-ART patients, deep sequencing identified a statistically significant higher prevalence of DRMs to nucleoside reverse transcriptase inhibitors (NRTIs) compared with Sanger sequencing. The difference was mainly due to the high prevalence of minority K65R and M184I mutations. Most virologic failure patients harboured DRMs against both NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). These minority DRMs contributed to the increased or enhanced virologic failures in these patients.

Conclusion: The results revealed the presence of minority DRMs to NRTIs and NNRTIs in specimens collected at baseline and virologic failure time points. These minority DRMs not only increased resistance levels to NRTIs and NNRTIs for the prescribed ART, but also expanded resistance to additional major first-line ART drugs. This study suggested that drug resistance testing that uses more sensitive technologies, is needed in this setting.


Keywords

deep sequencing; HIV-1 subtype C; ART-naïve; virologic failure; minority DR variants; Malawi

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