October 28, 2008 (Washington, DC) — A humanized monoclonal antibody, PRO 140, which targets CCR5-tropic virus, might be a viable approach to treating human immunodeficiency virus (HIV). Tantalizing data were presented here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

The results are from an interim analysis of the first 15 patients in a dose-escalation study. The patients had to have not started therapy or to have been off it for 12 weeks prior to enrollment. Their baseline averages were 35,480 HIV RNA copies/mL and a CD4 cell count of 403 cells/µL. A single dose of placebo or the monoclonal antibody was administered, and the patients were followed for 58 days.

Those receiving placebo showed a mean maximum 0.48 log10 reduction in HIV RNA (range, 0.15 - 0.73); that increased to +0.06 log10 by day 12. Patients receiving 5 mg/kg of PRO 140 saw a decline of 1.9 log10 (range, 1.44 - 2.17) for mean maximum log10 reductions and of 1.88 log10 for mean log10 changes. Patients receiving 10 mg/kg achieved a reduction of 2.17 log10 (range, 2.09 - 2.26) and 2.01 log10, respectively. Control of viremia slowly waned, but by day 22, patients who had received the larger dose of the monoclonal antibody still had a reduction in HIV RNA levels of 1.5 log10.

Lead author Jeffrey M. Jacobson, MD, from Drexel University College of Medicine in Philadelphia, Pennsylvania, told Medscape HIV/AIDS that the study confirmed and extended the initial single-dose study. The larger dose extended the duration of the antiviral effect, and studies of even larger doses are envisioned.

“This drug works differently from the other CCR5 inhibitors and potentially could be synergistic with them, or work on viruses that have developed resistance to them,” explained Dr. Jacobson.

The current intravenous administration of PRO 140 suggests dosing every 2 to 3 weeks, whereas modeling suggests that an increase in the dose might extend that to a month. The manufacturer and supporter of the study, Progenics, is investigating other possible modes of administration, including a transdermal patch that might administer a more steady state of the drug.

Dr. Jacobson said: “There are patients who clearly are not adhering to their regimens and not benefiting from them. Having a systemic treatment that could be administered at long enough intervals, and making it convenient enough, might have a place with patients who cannot or will not take their oral therapies” on the sustained basis that is required to prevent the development of viral resistance.

He also can envision a potential prophylactic use of the monoclonal antibody as a form of pre-exposure prophylaxis, at least in high-risk populations.

“If several of these [injectable or infusible] drugs could be developed and brought to clinical use, it would be much easier to provide directly observed therapy on a monthly basis” for hard-to-manage patients, Daniel Kuritzkes, MD, a Harvard University researcher and the conference organizer, told Medscape HIV/AIDS.

Dr. Kuritzkes noted that in vitro work “has demonstrated that the antibody is active against viruses that have developed resistance to small-molecule inhibitors, like maraviroc and vicriviroc.” But the drug candidate “faces a high bar” to widespread use.

The study was supported by a grant from the National Institutes of Health. Neither Dr. Jacobson nor Dr. Kuritzkes have disclosed any relevant financial relationships.

48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstract H-1269a. Presented October 26, 2008.

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