Substantial HIV reduction persists for 2-3 weeks with single dose of PRO-140 antibody

This article is more than 14 years old. Click here for more recent articles on this topic

A single dose of a monoclonal antibody that blocks the CCR5 receptor on human immune cells is enough to reduce HIV viral load by 90% (1 log10) for two to three weeks, pharmaceutical company Progenics announced today in a press release.

The monoclonal antibody product, called PRO 140, was tested in a phase 1b dose-escalation study in 39 HIV-positive individuals. Participants in the multicentre study were randomised to placebo or to one of three escalating single doses of PRO-140, which was administered intravenously.

At the two higher doses tested (2mg/kg and 5mg/kg) viral load fell by an average of 1.2 and 1.8 log10 respectively, with a maximum observed reduction of 2.5log10 in one patient who received the highest dose. All ten participants who received the 5mg/kg dose experienced a viral load reduction of at least 1log10.

Glossary

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

monoclonal antibody

Monoclonal antibodies are antibodies that are made by identical immune cells, which are all clones of a unique parent cell. Some of them have an effect on the immune system. 

receptor

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Nine days after the antibody was administered participants in the two higher dose groups had sustained viral load reductions: a mean of 1.04 and 1.7 log10 respectively.

Viral load remained suppressed at least 1log10 below baseline for two to three weeks before returning to baseline approximately 30 days after treatment.

"As an HIV/AIDS researcher for more than two decades, I was particularly gratified to see these results from our proprietary PRO 140 antibody, as they represent the largest reported single-dose mean reduction in viral load for any antiretroviral drug,” said Paul J. Maddon, Progenics’ chief executive.

Other products that block HIV’s use of the CCR5 receptor, such as maraviroc, are oral drugs that must be taken once or twice a day. PRO 140 represents the first antiretroviral drug that might permit weekly treatment, along with the nucleoside analogue elvucitabine. PRO 140 is also reported to be active against viruses that have evolved resistance to CCR5 antagonists such as maraviroc.