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Basic Characteristics of Mutations
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Mutation Site
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K70T |
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Mutation Site Sentence
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Twelve sequences had a TRAM not on the WHO SDRM list (A62V, n = 10;K70T, n = 2), although in four of these sequences the mutation was present with the K65R mutation. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
|
Treatment
|
tenofovir (TDF) |
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Location
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South Africa |
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Literature Information
|
|
PMID
|
31143879
|
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Title
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Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis
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Author
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Chimukangara B,Lessells RJ,Rhee SY,Giandhari J,Kharsany ABM,Naidoo K,Lewis L,Cawood C,Khanyile D,Ayalew KA,Diallo K,Samuel R,Hunt G,Vandormael A,Stray-Pedersen B,Gordon M,Makadzange T,Kiepiela P,Ramjee G,Ledwaba J,Kalimashe M,Morris L,Parikh UM,Mellors JW,Shafer RW,Katzenstein D,Moodley P,Gupta RK,Pillay D,Abdool Karim SS,de Oliveira T
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Journal
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EClinicalMedicine
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Journal Info
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2019 Mar 18;9:26-34
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Abstract
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BACKGROUND: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naive adults from South Africa. METHODS: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naive adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. FINDINGS: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11.9% (95% confidence interval (CI) 9.2-15.0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4-11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13-1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05-1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). INTERPRETATION: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. SOURCE OF FUNDING: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. DISCLAIMER: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.
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Sequence Data
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-
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