Autologous T-cell therapy based on a lentiviral vector expressing long antisense RNA targeted against HIV-1 env gene influences HIV replication and evolution in vivo

Alexander Pasternak,Nikolay Korokhov,Laurent Humeau,Vladimir Lukashov,Ben Berkhout

doi:10.1186/1742-4690-10-s1-o46

Alexander Pasternak, Nikolay Korokhov + Show 3 more

Open Access

https://doi.org/10.1186/1742-4690-10-s1-o46

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Abstract

Materials and methods Autologous CD4 T lymphocytes from HIV-infected subjects were genetically modified ex vivo with the vector, expanded, and 10-80 billion vector-modified cells were reinfused into patients. Longitudinal effects of the therapy on HIV-1 env evolution were analyzed in 17 subjects sampled both pre-infusion and monthly postinfusion for 6 to 12 months. Plasma-derived viral RNA from 144 samples was amplified, cloned, and the fulllength gp120 coding region was sequenced in 8-10 clones for each sample.

Highlights

We report the results of a Phase II clinical trial of VRX496, an HIV-based vector encoding a 937-nt long antisense (AS) RNA targeting the gp[120] coding region of HIV-1 env gene [1-3]
Materials and methods Autologous CD4+ T lymphocytes from HIV-infected subjects were genetically modified ex vivo with the vector, expanded, and 10-80 billion vector-modified cells were reinfused into patients
Longitudinal effects of the therapy on HIV-1 env evolution were analyzed in 17 subjects sampled both pre-infusion and monthly postinfusion for 6 to 12 months

Summary

Introduction

We report the results of a Phase II clinical trial of VRX496, an HIV-based vector encoding a 937-nt long antisense (AS) RNA targeting the gp[120] coding region of HIV-1 env gene [1-3]. Materials and methods Autologous CD4+ T lymphocytes from HIV-infected subjects were genetically modified ex vivo with the vector, expanded, and 10-80 billion vector-modified cells were reinfused into patients.

Results

Conclusion