Vicriviroc 24-week results in triple-class experienced R5-tropic patients
Mike Youle, for natap.org
After the disappointment of earlier vicriviroc studies it was comforting to see some positive news with the late-breaker presentation by Trip Gulick of the ACTG5211 study assessing 3 doses of vicriviroc (VCV) against placebo in the highly experienced R5-tropic patient population.
One hundred and eighteen subjects (median VL 36,380 copies/mL and CD4 146 cells/mm3) were randomised within the study and viral load declines were significantly greater in all three vicriviroc arms compared to placebo at day 14 and week 24 (p<0.05; ITT analysis).
Although not statistically significant the lower dose of 5mg resulted in more virologic failures and greater X4 virus emergence in that arm. Thirty three per cent of participants were already experienced to T-20 (enfurvitide). The group was 92% male, 66% Caucasian, 20% Black and 12% Hispanic.
Tropism at study entry was R5 only in 86% patients with only 10% with dual or mixed tropic. Considering that at screen, a few weeks before this, all were R5 only goes to show some of the limitations of the current technology to exactly decide the tropism of a patients virus. However, emerging data that even mixed/dual tropic virus responds to R5 receptor blockers may make the use of such an assay less vital.
Viral load reductions of >-1.5 logs were seen in at all VCV doses at week 24 (compared to -0.2log in OBT alone with CD4 increases of +84-142 compared to no change in the OBT alone group, and are detailed in Table 1.
When the responses were broken down by baseline tropism, good suppression was seen even in the X4/R5 tropic populations.
In a poster from Angela Sanone from Schering-Plough the effect of combining the vicriviroc with a range of boosted protease inhibitors (atazanavir, saquinavir, indinavir, fosamprenavir and tipranavir; also unboosted nelfinavir) was evaluated in a pharmacokinetic study in healthy volunteers. It seems that the addition of any of these agents has negligible effect on the key VCV PK parameters and no significant adverse events were reported. Clearly, further data will be needed with boosted lopinavir and with TMC114 (darunavir).
Table 1: Results of vivriviroc dose-finding study
|5mg QD||10mg QD||15mg QD||OBT only|
|Mean log change in viral load|
|Change in CD4|
|Tropism switch to X4/R5 or X4||27%||10%||7%||4%|
This article is part of a longer report on new antiretroviral studies at the conferences, available at:
- Gulick R, Su Z, Flexner C et al. ACTG 5211: phase II study of the safety and efficacy of vicriviroc in HIV-infected treatment-experienced subjects. Late breaker abstract THLB0217.
- Sansone A, Keung A, Tetteh E et al. Vicriviroc (VCV) pharmacokinetics (PK): lack of impact of ritonavir (RTV)-boosted protease inhibitors (PI). Poster abstract TUPE0074.