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IAS 2005: Rio de Janeiro; July 24-27

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The Body Covers: The 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment
Vicriviroc (SCH 417690, SCH-D), a CCR5 Antagonist, Generally Well Tolerated and Effective in 14-Day Monotherapy Study

July 26, 2005

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

IAS 2005 featured a bevy of oral presentations on CCR5 antagonists, a new class of HIV medications in development that seeks to prevent HIV from binding to the CCR5 cellular co-receptor, which facilitates HIV's entry into the host cell.

This study reported on the continuing clinical development of a Schering-Plough CCR5 antagonist termed SCH 417690, which was previously known as SCH-D and is now called vicriviroc. Several other companies are also developing antagonists of the CCR5 co-receptor for clinical use, including GlaxoSmithKline (which presented data on GSK873140 at this conference) and Pfizer, Inc. (which presented data on UK-427,857, a.k.a. maraviroc) among others. All these compounds are currently at a similar stage of development.

The current report represents a dose-finding study to establish the ability of vicriviroc to achieve antiviral effect in HIV-infected individuals. The study is similar in many ways to efforts by Pfizer and GlaxoSmithKline to better understand the antiviral profiles, pharmacokinetics and safety characteristics of their CCR5-inhibiting compounds.

This randomized, blinded study by D. Schuermann, of Charatie Hospital in Berlin, Germany, et al evaluated 48 HIV-infected individuals who were treated for 14 days with placebo or 1 of 3 twice-daily doses of vicriviroc monotherapy: 10 mg, 25 mg or 50 mg. The patients were divided into 3 cohorts, each consisting of 16 patients. In each cohort, 4 patients received placebo while 12 received one of the doses of vicriviroc.

Among the criteria for entry were that participants should only have detectable CCR5-tropic virus (i.e., no CXCR4-tropic virus), as monitored by the PhenoSense co-receptor assay developed by ViroLogic. Patients also needed to have a CD4+ cell count greater than 200 cells/mm3 and were either treatment naive or had previously received treatment but not for at least 8 weeks prior to enrollment in the current study.

Patients' mean baseline HIV RNA was 4.6 log10 copies/mL, and the mean baseline CD4+ cell count was 478 cells/mm3. Eighty-two percent of the study patients were male.

The results showed that vicriviroc was well tolerated, in doses up to 100 mg daily for 14 days, although 1 or 2 cases of seizures were reported transiently in several of the patients who received the drug. This situation will clearly need to be monitored over longer follow-up in more advanced clinical trials.

Most importantly, vicriviroc resulted in maintenance of steady-state Cmin values that were above the IC90 value for this compound as studied in tissue culture. Consistently, vicriviroc mediated a dose-related suppression of HIV RNA at all 3 doses that were studied, with a mean reduction in viral load of 1.62 log10 copies/mL after 14 days of treatment. Following this period, viral rebound to baseline slowly occurred over 2 weeks in the absence of treatment. An increase in CD4+ cell count was also observed during the period of study.

Clearly, these findings create an important rationale for the further clinical development of vicriviroc. A phase 2 study of vicriviroc is now recruiting treatment-experienced patients at sites throughout the United States; click here for more clinical trial information.

One final note: In this study, the compound was also shown to be effective against viral isolates of multiple subtypes -- not just subtype B -- which raises interesting questions as to the drug's potential usefulness in developing nations, where non-B-subtypes are prevalent. As resistance to existing antiretrovirals continues to increase in places such as Africa, Asia and South America, the availability of new drugs in new classes could become a critical issue.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Reference

Abstract: SCH 417690: antiviral activity of a potent new CCR5 receptor antagonist (Oral TuOa0205)
Authored by: D Schuermann, C Pechardscheck, R Rouzier, R Nougarede, G Faetkenheuer, I Ochlast, F Raffi, C Hoffman, W Greaves, A Sansone

Affiliations: Charatie Hospital, Berlin, Germany; CentreCap, Montpellier, France; University of Cologne, Cologne, Germany; Biotrial/University Hospital, Nantes and Rennes, France; University of Kiel, Kiel, Germany; Schering Plough Research Institute, Kenilworth, New Jersey, United States of America
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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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