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. MorozovAffiliated withHIV Variabilitat und moleculare Epidemiologie/P11, Robert Koch-InstitutVaccine Division, Institute of Human Virology Email author
- , Alexei V. MorozovAffiliated withHIV Variabilitat und moleculare Epidemiologie/P11, Robert Koch-Institut
- , Dirck SchürmannAffiliated withDepartment of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin
- , Heiko JessenAffiliated withMedical Practice
- , Claudia KüchererAffiliated withHIV Variabilitat und moleculare Epidemiologie/P11, Robert Koch-Institut
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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.
KeywordsHIV-1 Seroconverter Transmission chains env transmembrane protein T-20 Natural resistance
- 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
Volume 35, Issue 2 , pp 167-174
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- Springer US
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- Transmission chains
- env transmembrane protein
- Natural resistance
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- Author Affiliations
- 1. HIV Variabilitat und moleculare Epidemiologie/P11, Robert Koch-Institut, 20 Nordufer, 13353, Berlin, Germany
- 4. Vaccine Division, Institute of Human Virology, 725 W. Lombard Street, Baltimore, MD, 21201, USA
- 2. Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- 3. Medical Practice, Berlin, Germany