Background:  Inhibition of HIV entry by CCR5 antagonists is a new strategy currently studied for treatment of HIV infection. Apart from CD4⁺ cells, CCR5 is present on a variety of other immune cells (eg, CD8⁺ cells). Since hepatitis C virus (HCV) is largely controlled by CD8⁺ cells, there is theoretical concern that inhibition of CCR5 may negatively alter the course of patients co-infected with this virus.

Methods:  Aviremic patients for HIV (<400 copies/mL) receiving ritonavir (RTV) -boosted protease inhibitor (PI) containing ART with viremic HCV co-infection were enrolled into this randomized, double-blind, placebo-controlled multicenter study. We scheduled 40 subjects to receive 5 mg, 10 mg, or 15 mg vicriviroc (VCV) once daily, or placebo for 28 days in addition to their stable ART. Safety was the first objective of this study, and pharmacokinetics was a second objective. Clinical examination and laboratory tests (eg, HCV RNA, ALT, AST, GGT) were performed at days –1, 7, 14, 21, 28, 31, 33, 35, 42, and 49. An intention-to-treat analysis was performed including all randomized subjects with HCV RNA at all time points as the 1° parameter.

Results:  The study was terminated prematurely because of slow enrollment after 28 subjects (18 men, 10 women) enrolled. Median (range) baseline values were (n = 28):  41 (25 to 56) years for age, 436 (128 to 1240)/µL for CD4⁺ cells, and 4.9 (1.5 to 6.6) log₁₀ copies/mL for HCV RNA. No differences in increase of HCV RNA at day 28 (and on all other days studied) were observed between VCV arms and placebo. The median day 28 HCV RNA log₁₀ change from baseline (range) were 0.10 (–0.3 to 3.8), 0.21 (–1.3 to 1.9), 0.25 (–1.5 to 2.8), and –0.19 (–1.6 to 0.9) for the placebo, 5-mg, 10-mg, and 15-mg groups, respectively. Adverse events were equally distributed among placebo and VCV arms and were generally mild (headache, diarrhea). Transient elevations of ALT, AST, or GGT occurred in 4 patients on treatment (3 VCV, 1 placebo), 2 of whom were considered clinically significant (1 VCV 10 mg, 1 placebo). The VCV subject had an increase in ALT to twice baseline at day 28. Pharmacokinetic parameters (C_max, C_min, AUC) of VCV with RTV were dose dependent and comparable to healthy volunteers.

Conclusions:  This is the first study of a CCR5 antagonist in patients with HIV and HCV co-infection. Our results show that VCV was well tolerated and safe when administered for 28 days. There was no indication that VCV negatively influences HCV infection in terms of increasing HCV viral load.