New way of attacking HIV looks promising in early trial

A new monoclonal antibody treatment that blocks HIV’s ability to infect human cells is safe and effective, according to a preliminary trial in patients the results of which are published in the March 1^st edition of the Journal of Infectious Diseases

HGS004 is a human monoclonal antibody that binds to and inhibits the activity of the CCR5 receptor on the cell surface. HIV uses both the CCR5 and the CD4 receptors to gain entry to the cell but CCR5 is the primary receptor enabling HIV transmission and replication from the early stages of infection through to progression to AIDS.

Small-molecule CCR5 inhibitors like maraviroc and vicriviroc have already been shown to be effective HIV treatments, leading to maraviroc gaining a license last year.

But monoclonal antibody drugs have advantages compared to traditional small-molecule drugs. They can be dosed less frequently - biweekly or even monthly- and usually do not interfere with other drugs allowing a greater freedom of combination. They also should theoretically work against resistant strains. However, they have to be injected, rather than taken orally.

Preclinical research with HGS004 has shown that it binds tightly to human CCR5, prevents HIV entry and viral transmission.

But this new study has looked at its effects in 63 patients infected with CCR5-tropic HIV as a “proof of concept” study - a trial to demonstrate clinical efficacy with a small number of strictly selected patients.

All patients were randomised to receive a single intravenous dose of HGS004 at one of five doses – 0.4, 2, 8, 20 or 40 mg per kg body weight- or placebo. After 14 days 54% of patients in the 8, 20 and 40mg/kg group had a greater than log₁₀ drop in HIV RNA levels. In the 40mg/kg cohort four out of 10 patients had a greater than log10 reduction in HIV at day 28.

The antibody was well tolerated at all doses, with no increase in toxicities seen at higher doses.

The US authors say this study suggests HGS004 is safe and shows meaningful anti-HIV activity. But they suggest further studies should be carried out with HGS101 – a derivative of HGS004 which is five to ten times more potent but retains other characteristics of the original.