TY - JOUR
T1 - Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment
T2 - Follow-up study from the Lampang cohort
AU - Saeng-aroon, Siriphan
AU - Tsuchiya, Naho
AU - Auwanit, Wattana
AU - Ayuthaya, Panasda Isarangura Na
AU - Pathipvanich, Panita
AU - Sawanpanyalert, Pathom
AU - Rojanawiwat, Archawin
AU - Kannagi, Mari
AU - Ariyoshi, Koya
AU - Sugiura, Wataru
N1 - Funding Information:
We are grateful to all the participants of the Lampang cohort. We appreciate the technical assistance of Mrs. Arunratsamee Katesomboon, Mr. Amornsak Kladnil, Ms. Suthira Kasemsuk, Ms. Sriprai Seneewong-na yuthaya, Ms. Nutira Boonna, and Mr. Prapan Wongnamnong. We are indebted to Dr. Shiino Teiichiro, Dr. Shiro Ibe and Dr. Junko Shibata for guiding the analysis of genetic diversity of the RT gene. We also thank Ms. Claire Baldwin for her assistance in preparing the manuscript. This study was supported by The Ministry of Public Health Thailand , Ministry of Health, Labor and Welfare of Japan , and Human Sciences Grant.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - CRF01_AE
KW - Connection domain
KW - Drug resistance
KW - GPOvir
KW - Polymorphism
KW - RNase H
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U2 - 10.1016/j.antiviral.2010.04.001
DO - 10.1016/j.antiviral.2010.04.001
M3 - Article
C2 - 20382184
AN - SCOPUS:77953519153
VL - 87
SP - 22
EP - 29
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 1
ER -