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Abstract
Combination Stimulatory Approaches with Interleukin-7 Targeting Residual HIV-1 Disease: Highly Active Anti-Latency Therapy (HAALT)
Pomerantz R.1, Wang F.-X.1, Xu Y.1, Nunnari G.1
Introduction: These studies were utilized to develop combination anti-HIV-1 latency stimulatory approaches to induce viral outgrowth from resting CD4+ T lymphocytes and CD8-depleted PBMCs from patients on viral suppressive HAART; seeking down-modulation of viral reservoirs.
Methods: The methods used were ex vivo stimulatory approaches, using IL-7 combined with other activators including prostratin, IL-2, OKT3 and other non-tumorogenic phorbol esters. Viral outgrowth was monitored by p24 antigen expression, infectious unit assays, and RT-PCR. Stages of activation were analyzed via FACS, and effects on the T-cell mRNA and protein expression were evaluated using microarrays for genomics and proteomics.
Results: These studies, which extend the initial data on IL-7 (Pomerantz, R.J., et al., J.C.I., 2005), demonstrated that combination approaches with IL-7 and IL-2, or IL-7 with prostratin, lead to induced viral outgrowth from several cell-specific reservoirs within the peripheral blood of these patients. Strain-specificity for each of the individual activators and then combined approaches towards residual disease molecular perturbation was demonstrated by sequencing of the envelope glycoprotein and phylogenetic tree analyses. Of importance, partially or “low-level” activated CD4+ T-lymphocytes were demonstrated to express HIV-1 in these experiments.
Conclusions: These studies demonstrated that combination approaches will be necessary to both molecularly interrogate and stimulate various diverse viral strains from subtypes of CD4+ T-lymphocytes within the peripheral blood of virally-suppressed patients on HAART. As such, a combination “highly active anti-latency therapy (HAALT)” approach has been modeled in vitro, for now translational utility in humans.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
WePe8.13B01
Suggested Citation
"PomerantzR., et al.
Combination Stimulatory Approaches with Interleukin-7 Targeting Residual HIV-1 Disease: Highly Active Anti-Latency Therapy (HAALT).
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
WePe8.13B01"
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