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© Research
Publication : Journal of acquired immune deficiency syndromes (1999)

Increased polymorphism in the HR-1 gp41 env gene encoding the enfuvirtide (T-20) target in HIV-1 variants harboring multiple antiretroviral drug resistance mutations in the pol gene

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of acquired immune deficiency syndromes (1999) - 01 Jan 2007

Si-Mohamed A, Piketty C, Tisserand P, LeGoff J, Weiss L, Charpentier C, Kazatchkine MD, Bélec L

Link to Pubmed [PMID] – 17075396

J. Acquir. Immune Defic. Syndr. 2007 Jan;44(1):1-5

BACKGROUND: Sequence variations in HR-1 gp41 env gene region encoding the target for T-20 have previously been reported among patients naive to inhibitory fusion.

OBJECTIVE: To evaluate whether a previous therapeutic history of patients could have an impact on a differential evolution of the gp41 polymorphism.

METHODS: We assessed the genetic polymorphism within the critical HR-1 gp41 env gene region in HIV-1 variants from 108 T-20-naive patients (Groups I-III) and 12 patients receiving T-20 as part of a salvage regimen (Group IV). T-20-naive patients included 50 patients exhibiting variants harboring resistance mutations to NRTIs, NNRTIs, and PIs (Group I), 24 patients with variants harboring resistance mutations for NRTIs and/or NNRTIs (Group II), and 34 antiretroviral drug-naive patients (Group III).

RESULTS: In T-20-naive patients whose HIV harbored resistance mutations to NRTIs, NNRTIs, and/or PIs, the mean number of synonymous mutations (ds) per patient was decreased and the mean number of nonsynonymous (da) mutations per patient was increased, resulting in a significant decrease in the mean Sigmads/Sigmada ratio as compared with antiretroviral drug-naive patients (Group III; 4.1 vs. 11.6; P < 0.0001). The mean number of polymorphic mutations in HR-1 gp41 per patient was two-fold higher in patients exhibiting antiretroviral drug resistance mutations (Groups I and II) than in antiretroviral drug-naive patients (Group III; 0.41 vs. 0.20; P < 0.05).

CONCLUSION: Our observations indicate that the HR-1 gp41 T-20 target is subjected to high genetic variability, including intrinsic polymorphism and selection of T-20 resistance mutations under T-20 intake, that is increased by the presence of resistance mutations to NRTIs, NNRTIs, and/or PIs. Our data provide a basis for a potential impact of previous antiretroviral drug history on the therapeutic efficacy of T-20.

http://www.ncbi.nlm.nih.gov/pubmed/17075396