Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.
BACKGROUND
Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study.


METHODS
The present study was a double-blind, randomized phase 2 study of vicriviroc in treatment-experienced, human immunodeficiency virus (HIV)-infected subjects experiencing virologic failure while receiving a ritonavir-containing regimen with an HIV-1 RNA level >or=5000 copies/mL and CCR5-using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV-1 RNA levels at day 14; secondary end points included safety/tolerability and HIV-1 RNA changes at week 24.


RESULTS
One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log(10)) copies/mL and a median CD4 cell count of 146 cells/mm(3). At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log(10) copies/mL) were greater in the vicriviroc groups (-0.87 and -1.51 [5 mg], -1.15 and -1.86 [10 mg], and -0.92 and -1.68 [15 mg]) than in the placebo group (+0.06 and -0.29) (P<.01). Grade 3/4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo.


CONCLUSIONS
In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.
Gulick
Roy M
RM
Weill Medical College of Cornell University, New York, New York, NY, USA. rgulick@med.cornell.edu
Su
Zhaohui
Z
Flexner
Charles
C
Hughes
Michael D
MD
Skolnik
Paul R
PR
Wilkin
Timothy J
TJ
Gross
Robert
R
Krambrink
Amy
A
Coakley
Eoin
E
Greaves
Wayne L
WL
Zolopa
Andrew
A
Reichman
Richard
R
Godfrey
Catherine
C
Hirsch
Martin
M
Kuritzkes
Daniel R
DR
D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D015497:HIV-1 / Q000145:classification / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines; D011743:Pyrimidines; D012367:RNA, Viral; D019438:Ritonavir; C486781:vicriviroc