title: Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort.
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.
authors.affiliation: National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Siriphan
authors.initials: S
authors.lastname: Saeng-aroon
authors.forename: Naho
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Wattana
authors.initials: W
authors.lastname: Auwanit
authors.forename: Panasda Isarangura Na
authors.initials: PI
authors.lastname: Ayuthaya
authors.forename: Panita
authors.initials: P
authors.lastname: Pathipvanich
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
authors.forename: Archawin
authors.initials: A
authors.lastname: Rojanawiwat
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D019829:Nevirapine / Q000008:administration & dosage* / Q000494:pharmacology; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D018119:Stavudine / Q000008:administration & dosage* / Q000494:pharmacology; D013785:Thailand; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine