Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy : programmatic implications for countries phasing out stavudine
BACKGROUND: 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.
METHODS: 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.
RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ 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.
CONCLUSIONS: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:207 Suppl 2 |
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| Enthalten in: |
The Journal of infectious diseases - 207 Suppl 2(2013) vom: 15. Juni, Seite S70-7 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 02.08.2013 Date Revised 21.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jit114 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM22762484X |
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| 041 | |a eng | ||
| 100 | 1 | |a Tang, Michele W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy |b programmatic implications for countries phasing out stavudine |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.08.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ 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 | ||
| 520 | |a CONCLUSIONS: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AZT | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a NRTI | |
| 650 | 4 | |a TDF | |
| 650 | 4 | |a d4T | |
| 650 | 4 | |a drug resistance | |
| 650 | 4 | |a mutations | |
| 650 | 4 | |a nucleoside reverse transcriptase inhibitor | |
| 650 | 4 | |a stavudine | |
| 650 | 4 | |a subtypes | |
| 650 | 4 | |a tenofovir | |
| 650 | 4 | |a zidovudine | |
| 650 | 7 | |a Alkynes |2 NLM | |
| 650 | 7 | |a Anti-Retroviral Agents |2 NLM | |
| 650 | 7 | |a Benzoxazines |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Organophosphonates |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Reverse Transcriptase Inhibitors |2 NLM | |
| 650 | 7 | |a Zidovudine |2 NLM | |
| 650 | 7 | |a 4B9XT59T7S |2 NLM | |
| 650 | 7 | |a Nevirapine |2 NLM | |
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| 650 | 7 | |a Tenofovir |2 NLM | |
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| 700 | 1 | |a Ruxrungtham, Kiat |e verfasserin |4 aut | |
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| 700 | 1 | |a Wallis, Carole L |e verfasserin |4 aut | |
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| 700 | 1 | |a Hosseinipour, Mina C |e verfasserin |4 aut | |
| 700 | 1 | |a Ngo-Giang-Huong, Nicole |e verfasserin |4 aut | |
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