XVIII International AIDS Conference

Abstract

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Both immune activation and viral load are reduced within 28 days by VS411, the first antiviral-hyperactivation limiting therapeutic (AV-HALT) - a phase II study

E. Katabira1, P. Cahn2, J. Lange3, R. Maserati4, D. Baev5, S.A. Calarota5, D. De Forni5, M.R. Stevens6, J. Lisziewicz7, F. Lori5, for the VS411 Study Group

1Makerere Medical School, Kampala, Uganda, 2Fundación Huesped, Buenos Aires, Argentina, 3IATEC, Amsterdam, Netherlands, 4Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 5ViroStatics srl, Alghero (SS), Italy, 6ViroStatics srl, Princeton, NJ, United States, 7Genetic Immunity Kft., Budapest, Hungary

Background: Excessive immune activation drives disease progression and HIV-associated pathologies even with successful HAART. A new antiretroviral class, AV-HALTs, reduces both viral load and excessive immune activation. VS411, the first-in-class NRTI-based AV-HALT, combines low-dose, slow-release 2´,3´-dideoxyinosine (ddI) with low-dose hydroxycarbamide (HC) to accomplish both objectives with a favorable toxicity profile.
Methods: Multinational, double-blind, 28-day Phase IIa study: ART-naïve HIV-1-infected adults randomized into five VS411 dose arms. Activation/proliferation markers and HIV-specific T-cell responses analyzed by flow cytometry and ELISPOT. Results analyzed using ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t
tests.
Results: 58 subjects (median RNA: 4.50 log10, CD4: 406.5 cells/mm3, 50% female, 50% black) enrolled and analyzed (ITT-exposed). VS411 produced significant viral load reductions (P< .001), CD4 increases (P=.002), and significant, rapid immune activation marker reductions without suppression of HIV-specific immune responses. There were no SAEs/discontinuations or major differences between arms in clinical/laboratory safety, nor induction of nucleoside resistance.

VS411 results tables
[VS411 results tables]


Conclusions: VS411 was well-tolerated, increased CD4 counts and reduced VL, T-cell activation, and proliferating (Ki-67+) CD4+ T-cells without suppressing HIV-specific immune responses. The ddI200mg/HC900mg QD formulation (doses lower than traditionally investigated) demonstrated the greatest CD4+ increase (+135 cells), fewest AEs, and VL reduction of -1.47 log10. VS411 represents a new class, AV-HALTs, combining antiviral efficacy with novel, potentially beneficial reductions in the excessive immune system activation associated with HIV disease.


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