Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges.
BACKGROUND
Although HIV has become a treatable disease with near to normal life expectancy, the quest for the development of better tolerated drugs with simple dosing schedules and a high barrier to the emergence of drug resistance remains. Vicriviroc is a small-molecule chemokine receptor antagonist that inhibits the binding of R5-tropic HIV-1 to host cells at the CC-chemokine receptor 5 (CCR5) co-receptor, thus, preventing viral entry. CCR5 inhibitors are believed to possibly decrease inflammation from the immune system and thereby offer additional properties further to their antiretroviral efficacy.


METHODS
This review is based on a PubMed search covering the years 2005 - 2010 for pharmacokinetic, pharmacological and clinical data of vicriviroc.


RESULTS
In this review, the pharmacokinetic, pharmacological and clinical data of vicriviroc are presented. Moreover, the potential role of vicriviroc in the growing HIV armamentarium is discussed.


CONCLUSIONS
Vicriviroc is being developed to be administered in combination with a ritonavir-boosted protease inhibitor for patients with R5-tropic virus. Early clinical trials have established the safety of vicriviroc in both treatment-naive and -experienced R5-tropic HIV-1 infected individuals. Recently, two Phase III clinical trials in treatment-experienced patients failed to prove its superiority over available HIV medications. Phase III trials for treatment-naive patients are still under planning. Clearly, more favorable study results are needed to move vicriviroc into drug registration and approval.
Lenz
Johannes Carl Christoph
JC
University of Bonn, Medicine I, Sigmund-Freudstr. 25, Bonn 53105, Germany.
Rockstroh
Jürgen Kurt
JK
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D015897:Comorbidity; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000453:epidemiology; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines; D011743:Pyrimidines; C486781:vicriviroc