Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors

• Published in: AIDS (London) Vol. 17; no. 13; pp. 1889 - 1896
• Main Authors: SIRIVICHAYAKUL, Sunee, RUXRUNGTHAM, Kiat, UNGSEDHAPAND, Chaiwat, TECHASATHIT, Wichai, UBOLYAM, Sasiwimol, CHUENYAM, Theshinee, EMERY, Sean, COOPER, David, LANGE, Joep, PHANUPHAK, Praphan
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 05.09.2003
• Subjects: AIDS/HIV; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Didanosine - therapeutic use; Drug Resistance, Multiple; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Genotype; HIV Infections - drug therapy; HIV Infections - virology; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; Human viral diseases; Humans; Infectious diseases; Lamivudine - therapeutic use; Medical sciences; Mutation; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - therapeutic use; Stavudine - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Zidovudine - therapeutic use; Purine nucleoside; RNA-directed DNA polymerase; nucleoside reverse transcriptase inhibitors; HIV-1 virus; Stavudine; Microbiological investigation; genotypic resistance; Reverse transcriptase inhibitor; Antiviral; Nucleoside; Pyrimidine nucleoside; Immunopathology; Typing; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Genotype; Lamivudine; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Resistance; Nucleotidyltransferases; Viral disease; Dideoxynucleoside; Abacavir; Human immunodeficiency virus; Nucleosidic analog; Mutation; HIV-1 subtype A/E; Didanosine; Subtype; Zidovudine
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200309050-00007

To investigate genotypic drug resistance in HIV-1 subtype A/E infection associated with failure of double/triple-nucleoside reverse transcriptase (RT) inhibitor therapy. Patients from HIV-NAT 002 [stavudine (d4T)/didanosine (ddI) dose reduction study] and HIV-NAT 003 (zidovudine (ZDV)/lamivudine (3TC) versus ZDV/3TC/ddI) 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. Resistance mutations found in the d4T/ddI, ZDV/3TC, and ZDV/3TC/ddI 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/ddI to ZDV/3TC, group B ZDV/3TC to d4T/ddI, and group C ZDV/3TC/ddI 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). 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/ddI therapy led to a high incidence of V75T and L74V mutations. Switching from d4T/ddI 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.