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J Infect Dis. 2013 Jun 15;207 Suppl 2:S70-7. doi: 10.1093/infdis/jit114.

Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.

Author information

1
Division Infectious Diseases, Department of Medicine, Stanford University, California 94305, USA. micheletang@gmail.com

Abstract

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.

KEYWORDS:

AZT; HIV-1; NRTI; TDF; d4T; drug resistance; mutations; nucleoside reverse transcriptase inhibitor; stavudine; subtypes; tenofovir; zidovudine

PMID:
23687292
PMCID:
PMC3657117
DOI:
10.1093/infdis/jit114
[Indexed for MEDLINE]
Free PMC Article

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