Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients

Carmona, Rocı́o; Pérez-Álvarez, Lucı́a; Muñoz, Mercedes; Casado, Gema; Delgado, Elena; Sierra, María; Thomson, Michael M.; Vega, Yolanda; Parga, Elena Vázquez de; Contreras, Gerardo; Medrano, Leandro; Nájera, Rafael

doi:10.1016/j.jcv.2004.11.009

Cited by 61 publications

(62 citation statements)

References 20 publications

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“…Direct sequencing of 10 amplicons results in recovery of resistance-associated mutation (N43S) only in 01-004 (as shown by nearly equal double picks at the same position on chromatogram). Thus, matching reported 10% frequency of natural resistance to T-20 among subtype B infected patients [22]. Clonal analysis of the amplicons confirmed this mutation in two out of five examined clones, giving quasiequal amount of resistant to non-resistant virus variants in 01-004.…”

Section: Diversity In Fd-hr1 Domains In Viruses From Therapynaive Sermentioning

confidence: 64%

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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

Morozov

Schürmann

et al. 2007

Virus Genes

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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.

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Section: Diversity In Fd-hr1 Domains In Viruses From Therapynaive Sermentioning

confidence: 64%

“…Limited data are available concerning TM variation and natural resistance to T-20 therapy in naïve individuals and seroconverters [21][22][23]. Nothing is known about horizontal transmission of T-20-resistant virus if present together with a sensitive virus strains.…”

Section: Introductionmentioning

confidence: 99%

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

Morozov

Schürmann

et al. 2007

Virus Genes

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“…The major mutations identified include G36D/S, I37 V, V38A/E/M, Q39H/R, Q40H, N42T, and N43D. [3][4][5] Other secondary mutations including N126K, E137K and S138A in the HR2 region were also described to associate with ENF resistance. 6 ENF resistanceassociated mutations have been reported in HAART-experienced patients but very uncommonly in antiretroviral treatment-naïve experienced patients, 3 samples were collected from a patient underwent different ENF treatment intervals (pre-ENF, on ENF and post-ENF).…”

Section: Introductionmentioning

confidence: 99%

High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong

Leung

Chen

Wong

et al. 2010

Journal of Clinical Virology

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“…However, the complete success of these strategies has been limited by the appearance of resistant strains. Interpretation of resistanceassociated mutation patterns is becoming increasingly complex, considering the variety of therapy regimens, the influence that certain mutations might have even on resistance to drugs to which the patient has never been exposed (natural resistance, cross-resistance, and resistance transmission) [Ná jera et al, 1994[Ná jera et al, , 1995Lech et al, 1996;Carmona et al, 2005;Turner and Wainberg, 2006], and the persistence of resistance mutations in patients previously treated with different drugs. Thus, drug-resistance is now a widespread and growing problem, that not only involves antiretroviral-treated patients, but also drug-naïve individuals infected with HIV resistant strains.…”

Section: Introductionmentioning

confidence: 99%

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

Ríos

Delgado

Pérez-Álvarez

et al. 2007

Journal of Medical Virology

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This study reports the analysis of human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) coding sequences from 136 HIV-1-infected subjects from Chile, 66 (49%) of them under antiretroviral (ARV) treatment. The prevalence of mutations conferring high or intermediate resistance levels to ARVs was 77% among treated patients and 2.5% among drug-naïve subjects. The distribution of resistance prevalence in treated patients by drug class was 61% to nucleoside RT inhibitors, 84% to nonnucleoside RT inhibitors, and 46% to PR inhibitors. Phylogenetic analysis revealed that 115 (85%) subjects were infected with subtype B viruses, 1 with a subtype F1 virus, and 20 (15%) carried BF intersubtype recombinants. Most BF recombinants grouped into two clusters, one related to CRF12_BF, while the other could represent a new circulating recombinant form (CRF). In conclusion, this is the first report analysing the prevalence of ARV resistance which includes patients under HAART from Chile. Additionally, phylogenetic analysis of the PR-RT coding sequences reveals the presence of BF intersubtype recombinants.

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Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients

Cited by 61 publications

References 20 publications

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

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

High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong

Antiretroviral drug resistance and phylogenetic diversity of HIV‐1 in Chile

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