Vicriviroc: a CCR5 antagonist for treatment-experienced patients with HIV-1 infection.
BACKGROUND
Despite the availability of 31 antiretroviral agents or fixed-dose combinations in the United States and European Union, there is a continuing need for antiretroviral agents with high genetic barriers to resistance, simple dosing schedules, and favorable tolerability and safety profiles. Vicriviroc is a small-molecule chemokine receptor antagonist that inhibits the binding of R5-tropic HIV-1 to host cells at the CCR5 co-receptor, thus preventing viral entry.


OBJECTIVE
To present an evidence-based assessment of the clinical efficacy, pharmacokinetics, and safety profile of vicriviroc.


METHODS
We discuss available peer-reviewed publications as well as preliminary data presented at relevant scientific meetings.


CONCLUSIONS
Vicriviroc has a favorable pharmacokinetic profile with a half-life that enables once-daily dosing. Minimal drug interactions have been demonstrated with other available antiretrovirals. Early clinical trials have established the safety of vicriviroc in both treatment-naive and treatment-experienced R5-tropic HIV-1 infected individuals. A Phase II study in treatment-experienced patients demonstrated early efficacy of 30 mg vicriviroc in a regimen containing a ritonavir-boosted protease inhibitor (PI/r). Phase III studies using the 30-mg PI/r dosing paradigm in R5-tropic treatment-experienced patients have completed 48 weeks, but data are not yet available. These results will further elucidate the role of vicriviroc in the treatment of HIV-1 infected individuals.
Kümmerle
Tim
T
Department of Internal Medicine I, University of Cologne, 50937 Köln, Germany.
Lehmann
Clara
C
Hartmann
Pia
P
Wyen
Christoph
C
Fätkenheuer
Gerd
G
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053586:Virus Internalization / Q000187:drug effects
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines; D011743:Pyrimidines; C486781:vicriviroc