XVIII International AIDS Conference

Abstract

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Miltefosine efficiently inhibit HIV-1 transmission from human primary monocyte-derived dendritic cells to CD4+ T Cells

R. Garg, M.J. Tremblay

Laval University, Medical Biology, Quebec, Canada

Background: Miltefosine (Hexadecylphosphocholine) is a phosphorylcholine ester of hexadecanol, a membrane-active, alkylphospholipid. Miltefosine is an antiprotozoal drug. Miltefosine was originally discovered and synthesized as an antineoplastic. Dendritic cells (DCs) are versatile antigen-presenting cells, play a key role in HIV-1 infection and dissemination. Indeed, it has been reported that HIV-1 is efficiently transferred from DCs to CD4+ T cells via different routes (early transfer & late transfer). In the present study, we investigated the influence of miltefosine on virus interaction with physiologically relevant human monocyte-derived dendritic cells.
Methods: Primary human monocyte-derived immature dendritic cells (iDCs) were first pulsed with NL4-3Balenv (fully competent R5-tropic virus) for 1 hour and washed. Next iDCs were incubated with or without autologous CD4+ T cells and either left untreated or treated with different doses of miltefosine. Viral replication was assayed by measuring the cell-free p24 content at different time interval. To define whether Miltefosine are affecting the early and/or late transfer phase, iDCs were first treated with the antiretroviral drug efavirenz (EFV) before pulsing with virions.
Results: We demonstrate that miltefosine significantly inhibit HIV-1 transmission from iDCs to CD4+ T cells. We provide evidence that miltefosine exert an effect on both early and late phase transfer event.
Conclusions: Altogether, these findings represent a new functional role of miltefosine for HIV-1 transmission. Our data set the stage for future development of this class of drug for better treatment of HIV-1.


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