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

被引：10

作者：

Saeng-aroon, Siriphan ^{[2
]}

Tsuchiya, Naho ^{[4
]}

Auwanit, Wattana ^{[2
]}

Ayuthaya, Panasda Isarangura Na ^{[2
]}

Pathipvanich, Panita ^{[3
]}

Sawanpanyalert, Pathom ^{[2
]}

Rojanawiwat, Archawin ^{[2
]}

Kannagi, Mari ^{[5
]}

Ariyoshi, Koya ^{[4
]}

Sugiura, Wataru ^{[1
,6
,7
]}

机构：

[1] Nagoya Med Ctr, Clin Res Ctr, Dept Infect & Immunol, Naka Ku, Nagoya, Aichi 4600001, Japan

[2] Minist Publ Hlth, Natl Inst Hlth, Dept Med Sci, Nonthaburi, Thailand

[3] Lampang Hosp, Lampang, Thailand

[4] Nagasaki Univ, Global COE Program, Dept Clin Med, Inst Trop Med, Nagasaki 852, Japan

[5] Tokyo Med & Dent Univ, Dept Immunotherapeut, Tokyo, Japan

[6] Nagoya Grad Sch Med, Dept AIDS Res, Nagoya, Aichi, Japan

[7] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan

来源：

ANTIVIRAL RESEARCH | 2010年 / 87卷 / 01期

关键词：

CRF01_AE; Polymorphism; Drug resistance; Connection domain; RNase H; GPOvir; IMMUNODEFICIENCY-VIRUS TYPE-1; RNASE-H DOMAINS; REVERSE-TRANSCRIPTASE; CONNECTION DOMAIN; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; NUCLEOSIDE ANALOGS; INITIAL REGIMEN; HIV-1; RT; ZIDOVUDINE;

D O I：

10.1016/j.antiviral.2010.04.001

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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-naive 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-nave prior to GPOvir (naive group), and 30 had previous ART (exposed group). To clarify the effect of previous ART in drug-resistant acquisition pathways, naive and exposed groups were compared. The exposed group had predominantly thymidine analogue-related mutations, whereas the naive group had a higher prevalence of Q151M and K103N mutations. M184V lamivudine resistance was most frequent in both naive 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. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：22 / 29

页数：8