ias 2013 conference, page-5

The abstract has been released on the IAS 2103 iphone / android app.

Background: Biotron Limited's lead compound,BIT225, blocks Vpu ion channel activity and has anti-HIV-1 activity in vitro. Theantiviral effect is greater in cells of the monocyte lineage; with circulatingmonocytes able to differentiate into tissue resident macrophages, a keycellular reservoir of HIV-1. BIT225 is anovel antiviral drug that disrupts viral assembly within the host cell,resulting in a substantial loss of infectivity of the progeny virus. BIT225 wasfound to be well tolerated in a Phase I clinical trial in healthy volunteers.This study is the first clinical evaluation of BIT225 therapy in HIV-1 infectedsubjects.

Methods: BIT004 is a phase 1b/2a, placebo-controlled, randomized study ofthe safety, pharmacokinetics and antiviral activity of BIT225 in 21 HIV-1 + , antiretroviral therapy naïve subjects. Subjectsreceived BIT225 (400 mg BID) or placebo treatment for 10 days (randomized 2:1).Twenty-one subjects were enrolled and completed treatment. To explore the potential of BIT225 to reducethe viral burden within the monocyte reservoir, CD14 + monocytes isolated from the peripheral blood on days 0, 5, 10 and 20, were cocultured ex vivo withMT4 T cells. De novo HIV-1 replication was measured byp24 activity of released virus into the culture supernatant to day 25 ofcoculture. In addition, monocyte sampleswere collected for RT-PCR HIV-1 single copy assay analysis. Results: Cocultures were established with monocytes isolated at days 0, 5, 10and 20 for both BIT225 treated and placebo controls. Placebo controls demonstrated similar levelsof infectious virus released from the monocytes, at all time points, indicativeof a stable level of infection. BIT225 treatment resulted in a reduced level ofHIV-1 transmission from this compartment. When the BIT225 treated patients were grouped at baseline into thosewith high versus low viral load (using the median), BIT225 resulted in asignificant reduction in the amount of infectious virus released from themonocytes in the higher viral load cohort.

Conclusions: This study's unique designdemonstrates that BIT225 can significantly reduce the dissemination of HIV-1 frominfected monocytes. Potentially this hasimportant ramifications for diminishing the seeding/re-seeding of the viralreservoir.