Drug-resistant mutation patterns in CRF01_AE cases that failed d4T + 3TC + nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort

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• 作者：Siriphan Saeng-aroon ; Naho Tsuchiya ; Wattana Auwanit ; Panasda Isarangura Na Ayuthaya ; Panita Pathipvanich ; Pathom Sawanpanyalert ; Archawin Rojanawiwat ; Mari Kannagi ; Koya Ariyoshi ; Wataru Sugiura
• 关键词：CRF01_AE ; Polymorphism ; Drug resistance ; Connection domain ; RNase H ; GPOvir
• 刊名：Antiviral Research
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：87
• 期：1
• 页码：22-29
• 全文大小：436 K

文摘

HIV/AIDS patients are treated in Thailand's national antiretroviral treatment (ART) program with a generic combination tablet of stavudine, lamivudine, and nevirapine (GPOvir). To determine GPOvir-resistant mutations, HIV-1 sequences of 59 GPOvir-failure cases from the Lampang cohort were compared with sequences from 76 randomly selected ART-naïve cases. The GPOvir-failure cases had not only known stavudine-, lamivudine- and nevirapine-resistant mutations, but also V118I, G196E, and H221Y. Among the 59 GPOvir-failure cases, 29 were ART-naïve prior to GPOvir (naïve group), and 30 had previous ART (exposed group). To clarify the effect of previous ART in drug-resistant acquisition pathways, naïve and exposed groups were compared. The exposed group had predominantly thymidine analogue-related mutations, whereas the naïve group had a higher prevalence of Q151M and K103N mutations. M184V lamivudine resistance was most frequent in both naïve and exposed groups. To identify which mutations in CRF01_AE pol were polymorphisms, the connection and RNase domains were also analyzed. CRF01_AE-specific polymorphisms were found in 19 residues, and GPOvir-failure cases had significantly higher frequency of N348I, E399D, P537S, and I542M. Our results expand identification of mutations in CRF01_AE pol that are polymorphisms by also analyzing the connection and RNase H domains.