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    <abstract>The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, &gt;= two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.</abstract>
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    <subject>
      <topic>HIV-1</topic>
      <topic>drug resistance</topic>
      <topic>mutations</topic>
      <topic>nucleoside reverse transcriptase</topic>
      <topic>inhibitor</topic>
      <topic>NRTI</topic>
      <topic>stavudine</topic>
      <topic>d4T</topic>
      <topic>zidovudine</topic>
      <topic>AZT</topic>
      <topic>tenofovir</topic>
      <topic>TDF</topic>
      <topic>subtypes</topic>
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        <title>Journal of Infectious Diseases</title>
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          <number>207</number>
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        <detail type="volume">
          <number>2</number>
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          <list> S70-S77</list>
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        <dateIssued>2013</dateIssued>
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      <identifier type="issn">0022-1899</identifier>
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    <identifier type="uri">https://www.documentation.ird.fr/hor/fdi:010060440</identifier>
    <identifier type="doi">10.1093/infdis/jit114</identifier>
    <identifier type="issn">0022-1899</identifier>
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