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Title: Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors
Authors: Sunee Sirivichayakul
Kiat Ruxrungtham
Chaiwat Ungsedhapand
Wichai Techasathit
Sasiwimol Ubolyam
Theshinee Chuenyam
Sean Emery
David Cooper
Joep Lange
Praphan Phanuphak
Chulalongkorn University
The HIV Netherlands Australia Thailand Research Collaboration
Mahidol University
Kirby Institute
Natl. AIDS Therapy Evaluation Centre
Keywords: Immunology and Microbiology
Issue Date: 5-Sep-2003
Citation: AIDS. Vol.17, No.13 (2003), 1889-1896
Abstract: Objectives: To investigate genotypic drug resistance in HIV-1 subtype A/E infection associated with failure of double/triple-nucleoside reverse transcriptase (RT) inhibitor therapy. Methods: Patients from HIV-NAT 002 [stavudine (d4T)/didanosine (ddl) dose reduction study] and HIV-NAT 003 (zidovudine (ZDV)/lamivudine (3TC) versus ZDV/3TC/ddl) whose HIV-1 RNA was > 1000 copies/ml at week 48 and/or week 96 were tested for genotypic resistance. In both studies, after 48 weeks, patients were switched to the other dual or triple-nucleoside RT inhibitor (NRTI) either according to randomization or to the occurrence of virological failure. Results: Resistance mutations found in the d4T/ddl, ZDV/3TC, and ZDV/3TC/ddl groups: none at baseline; at week 48, nucleoside analogue mutations (NAM), 2/17 (12%), 2/10 (20%), and 1/8; Q151M complex, 3/17 (18%), 0%, and 0%; M184V, 0%, 10/10 (P < 0.001), 3/8; V75T, 3/17 (18%), 0%, and 0%; L74V, 3/7 (18%), 0%, and 0%, respectively. At week 96, among the switchers, i.e., group A d4T/ddl to ZDV/3TC, group B ZDV/3TC to d4T/ddl, and group C ZDV/3TC/ddl to d4T/3TC/abacavir: NAM, 12/21 (57%), 4/7 and 1/3; Q151M, 4/21 (19%), 0% and 1/3, respectively. Interestingly, four or more NAM were observed in a higher proportion in group A (4/17 versus none in the others). Conclusions: Multi-NRTI resistance (NAM and Q151M) and M184V (only in 3TC failure) are commonly found in HIV-1 subtype A/E infection associated with NRTI failure. Suboptimal d4T/ddl therapy led to a high incidence of V75T and L74V mutations. Switching from d4T/ddl to ZDV/3TC may be associated with a higher incidence of four or more NAM. Thus, suboptimal and dual NRTI therapy is not recommended for global application. © 2003 Lippincott Williams & Wilkins.
ISSN: 02699370
Appears in Collections:Scopus 2001-2005

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