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Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.
J Infect Dis. 2013 Jun 15; 207 Suppl 2:S70-7.JI

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.

Authors+Show Affiliations

Division Infectious Diseases, Department of Medicine, Stanford University, California 94305, USA. micheletang@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23687292

Citation

Tang, Michele W., et al. "Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated With First-line Stavudine-containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine." The Journal of Infectious Diseases, vol. 207 Suppl 2, 2013, pp. S70-7.
Tang MW, Rhee SY, Bertagnolio S, et al. Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. J Infect Dis. 2013;207 Suppl 2:S70-7.
Tang, M. W., Rhee, S. Y., Bertagnolio, S., Ford, N., Holmes, S., Sigaloff, K. C., Hamers, R. L., de Wit, T. F., Fleury, H. J., Kanki, P. J., Ruxrungtham, K., Hawkins, C. A., Wallis, C. L., Stevens, W., van Zyl, G. U., Manosuthi, W., Hosseinipour, M. C., Ngo-Giang-Huong, N., Belec, L., ... Shafer, R. W. (2013). Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. The Journal of Infectious Diseases, 207 Suppl 2, S70-7. https://doi.org/10.1093/infdis/jit114
Tang MW, et al. Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated With First-line Stavudine-containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine. J Infect Dis. 2013 Jun 15;207 Suppl 2:S70-7. PubMed PMID: 23687292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine. AU - Tang,Michele W, AU - Rhee,Soo-Yon, AU - Bertagnolio,Silvia, AU - Ford,Nathan, AU - Holmes,Susan, AU - Sigaloff,Kim C, AU - Hamers,Raph L, AU - de Wit,Tobias F Rinke, AU - Fleury,Herve J, AU - Kanki,Phyllis J, AU - Ruxrungtham,Kiat, AU - Hawkins,Claudia A, AU - Wallis,Carole L, AU - Stevens,Wendy, AU - van Zyl,Gert U, AU - Manosuthi,Weerawat, AU - Hosseinipour,Mina C, AU - Ngo-Giang-Huong,Nicole, AU - Belec,Laurent, AU - Peeters,Martine, AU - Aghokeng,Avelin, AU - Bunupuradah,Torsak, AU - Burda,Sherri, AU - Cane,Patricia, AU - Cappelli,Giulia, AU - Charpentier,Charlotte, AU - Dagnra,Anoumou Y, AU - Deshpande,Alaka K, AU - El-Katib,Ziad, AU - Eshleman,Susan H, AU - Fokam,Joseph, AU - Gody,Jean-Chrysostome, AU - Katzenstein,David, AU - Koyalta,Donato D, AU - Kumwenda,Johnstone J, AU - Lallemant,Marc, AU - Lynen,Lutgarde, AU - Marconi,Vincent C, AU - Margot,Nicolas A, AU - Moussa,Sandrine, AU - Ndung'u,Thumbi, AU - Nyambi,Phillipe N, AU - Orrell,Catherine, AU - Schapiro,Jonathan M, AU - Schuurman,Rob, AU - Sirivichayakul,Sunee, AU - Smith,Davey, AU - Zolfo,Maria, AU - Jordan,Michael R, AU - Shafer,Robert W, PY - 2013/5/21/entrez PY - 2013/5/25/pubmed PY - 2013/8/3/medline KW - AZT KW - HIV-1 KW - NRTI KW - TDF KW - d4T KW - drug resistance KW - mutations KW - nucleoside reverse transcriptase inhibitor KW - stavudine KW - subtypes KW - tenofovir KW - zidovudine SP - S70 EP - 7 JF - The Journal of infectious diseases JO - J Infect Dis VL - 207 Suppl 2 N2 - 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. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/23687292/Nucleoside_reverse_transcriptase_inhibitor_resistance_mutations_associated_with_first_line_stavudine_containing_antiretroviral_therapy:_programmatic_implications_for_countries_phasing_out_stavudine_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jit114 DB - PRIME DP - Unbound Medicine ER -