Virus Genes

, Volume 35, Issue 2, pp 167–174

Transmembrane protein polymorphisms and resistance to T-20 (Enfuvirtide, Fuzeon®) in HIV-1 infected therapy-naive seroconverters and AIDS patients under HAART-T-20 therapy

  • Vladimir A. Morozov
  • Alexei V. Morozov
  • Dirck Schürmann
  • Heiko Jessen
  • Claudia Kücherer
Article

DOI: 10.1007/s11262-007-0098-8

Cite this article as:
Morozov, V.A., Morozov, A.V., Schürmann, D. et al. Virus Genes (2007) 35: 167. doi:10.1007/s11262-007-0098-8

Abstract

The human immunodeficiency virus type 1 fusion inhibitor T-20 (Enfuvirtide, Fuzeon®) has recently been introduced into clinical practice. T-20 in combination with HAART efficiently inhibits HIV-1 replication, however T-20 resistance has been reported and the number of confirmed resistant-associated mutations is growing.

In this study we aimed to analyze HIV-1 gp41 transmembrane protein (TM) variability and primary resistance to T-20 in plasma viruses from 10 HIV-1 subtype B infected homosexuals. Nine out of ten were documented seroconverters. Nine individuals (including one long time infected therapy naïve individual) were part of four linked virus infection chains. We also examined TM polymorphism in two AIDS patients under HAART and T-20 therapy. Obtained TM amplicons were examined for minor variants by clonal analysis.

Sequences polymorphism of the N-terminal regions of the fusion domain (FD) and the heptad repeat 2 (HR2) domain were demonstrated in examined seroconverters. Analysis of the heptad repeat 1 (HR1) domain revealed T-20 resistance in cloned sequences from 3/10 individuals. In two individuals these mutations were present as minor viral quasispecies. Transmission of the resistant virus to the sexual partner was traced in virus infection chain.

Baseline TM amplicons (population sequence) and clones from two patients under HAART did not contain T-20 resistance associated mutations. After onset of T-20 therapy only resistant viruses were identified in plasma from the patients. As shown by clonal analysis of plasma from one patient, treatment interruption results in viruses reverting to a T-20-sensitive genotype.

Keywords

HIV-1 Seroconverter Transmission chains env transmembrane protein T-20 Natural resistance 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Vladimir A. Morozov
    • 1
    • 4
  • Alexei V. Morozov
    • 1
  • Dirck Schürmann
    • 2
  • Heiko Jessen
    • 3
  • Claudia Kücherer
    • 1
  1. 1.HIV Variabilitat und moleculare Epidemiologie/P11Robert Koch-InstitutBerlinGermany
  2. 2.Department of Internal Medicine/Infectious Diseases and Pulmonary MedicineCharité-Universitätsmedizin BerlinBerlinGermany
  3. 3.Medical PracticeBerlinGermany
  4. 4.Vaccine DivisionInstitute of Human VirologyBaltimoreUSA

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