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

Siriphan Saeng-aroon, Naho Tsuchiya, Wattana Auwanit, Panasda Isarangura Na Ayuthaya, Panita Pathipvanich, Pathom Sawanpanyalert, Archawin Rojanawiwat, Mari Kannagi, Koya Ariyoshi, Wataru Sugiura

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalAntiviral Research
Volume87
Issue number1
DOIs
Publication statusPublished - 2010 Jul
Externally publishedYes

Keywords

  • CRF01_AE
  • Connection domain
  • Drug resistance
  • GPOvir
  • Polymorphism
  • RNase H

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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