Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

作者：Tang Michele W^*; Rhee Soo Yon; Bertagnolio Silvia; Ford Nathan; Holmes Susan; Sigaloff Kim C; Hamers Raph L; de Wit Tobias F Rinke; Fleury Herve J; Kanki Phyllis J; Ruxrungtham Kiat; Hawkins Claudia A; Wallis Carole L; Stevens Wendy; van Zyl Gert U; Manosuthi Weerawat; Hosseinipour Mina C; Ngo Giang Huong Nicole; Belec Laurent; Peeters Martine; Aghokeng Avelin; Bunupuradah Torsak; Burda Sherri; Cane Patricia; Cappelli Giulia; Charpentier Charlotte

来源：Journal of Infectious Diseases, 2013, 207(suppl_2): S70-S77.

DOI：10.1093/infdis/jit114

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

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. %26lt;br%26gt;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. %26lt;br%26gt;Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, %26gt;= 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. %26lt;br%26gt;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.

• 出版日期2013-6-15
• 单位西北大学