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Abstract
Residual HIV-1 disease eradication (rhide) trial: an HIV-1 reservoir eradication approach in humans using stimulatory and novel intensification therapy
R J Pomerantz1, M Otero1, G Nunnari1, A Malin1, C Coates1, C Dascenzo1, J DeSimone1, T J Babinchak1, H Zhang1, G Dornadula1, D Culnan1, J Sullivan1, Y Xu1, J Stern2, W Cavert3, A T Haase3, J Kulkosky4
1Thomas Jefferson University, Philadelphia, PA 19107, United States; 2Pennsylvania Hospital, Infectious Disease Section, Philadelphia, PA 19107, United States; 3University of Minnesota Medical School, Minneapolis, MN 55455, United States; 4Thomas Jefferson University, Philadelphia, PA 19107, United States
B>Background: HAART has led to significant changes in mortality and morbidity. Nevertheless, due to two main molecular mechanisms of viral persistence, cryptic viral replication and proviral latency in resting T-cells, HAART does not eradicate HIV-1. These mechanisms of residual reservoir disease in vivo were approached with a rationally-designed combination therapeutic protocol.
B>Methods: Three patients with HIV-1 infection on HAART, with less than 50 copies/ml of plasma viral RNA, were enrolled. They continued their baseline HAART, and DDI plus hydroxyurea (HU) were added as novel intensification to attack cryptic viral replication. The patients were then treated in our bone marrow transplant unit with low dose OKT3, followed by a two week course of subcutaneous IL-2 to stimulate latent provirus. Plasma viral RNA and 2-LTR DNA circles were analyzed via quantitative RT and DNA-PCR respectively, with PBMC co-cultures to detect replication-competent virus.
B>Results: All treated patients had only modest side effects. Replication-competent virus was undetectable after treatment and plasma viral RNA also became undetectable in each of these patients, using an ultrasensitive laboratory RT-PCR assay which quantitates to 5 copies/ml. Tonsillar biopsies were performed and no in situ hybridization for HIV-1-specific RNA was detected. HIV-1 2-LTR DNA circles, which suggest on-going viral replication, also disappeared after treatment. The first two patients have already been given trials off all anti-retroviral therapy, with one patient having no viral rebound for several months.
B>Conclusions: This represents the first translational research protocol to combine both novel intensification and stimulatory therapeutics to deplete residual viral reservoirs in vivo. This trial demonstrates that intensification and stimulatory therapy in eradication protocols, when properly designed and at precise doses, can be given safely to patients.
The XIV International AIDS Conference
Abstract no.
WePeB5894
Suggested Citation
" R J Pomerantz , , et al.
Residual HIV-1 disease eradication (rhide) trial: an HIV-1 reservoir eradication approach in humans using stimulatory and novel intensification therapy.
Poster Exhibition:
The XIV International AIDS Conference:
Abstract no.
WePeB5894"
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