IAS: Vicriviroc still effective at 48 weeks in treatment-experienced, but relationship with cancer remains uncertain

Encouraging data demonstrating the enduring antiviral efficacy of vicriviroc in treatment-experienced patients was presented to the 4^thInternational AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention Conference in Sydney on Tuesday July 24^th. However, investigators remain uncertain about the drug’s relationship with cancer. A total of eight malignancies have now been reported amongst vicriviroc-treated patients compared to two in the placebo arm.

Vicriviroc (VCV), is a novel CCR5 inhibitor being developed by Schering-Plough, and is being examined in the ACTG 5211 trial. Investigators presented 48-week data to the Sydney conference, updating the 24-week data presented at the Sixteenth International AIDS Conference in Toronto in August 2006. A year’s worth of data represents the longest follow-up available for a CCR5 inhibitor-based regimen in treatment-experienced patients. It is planned to follow patients in the ACTG 5211 trial for five years.

The study enrolled 118 treatment-experienced patients who were failing therapy. All patients had R5-tropic virus, as confirmed with the Trofile assay. The median viral load at baseline was 4.56 log₁₀ and the CD4 cell count was 146 cells/mm³. To start, participants remained on their failing therapy and were randomised to receive either VCV at 5, 10, or 15 mg daily or a placebo. After two weeks of this regimen, the background therapy was optimised on the basis of resistance tests conducted at baseline. All patients took low dose ritonavir as this drug is known to boost levels of VCV.

Forty-eight week data were reported on 88 participants: 30 receiving 10 mg VCV daily, 30 receiving 15 mg VCV daily and 28 receiving the placebo. The 5 mg VCV arm was stopped early at the behest of the study monitoring committee. In the groups continuing, 82% of participants (23 of 28) in the placebo arm stopped treatment early, compared with between 30% of patients taking the 10mg dose of VCV and 37% taking the 15mg dose.

Participants were monitored for changes in viral load and CD4 cell count. Also recorded were the proportion of participants with an undetectable viral load (below 50 copies/ml) and the proportion reporting virologic failure. Participants in the placebo arm were allowed to cross over to the VCV arm following virologic failure.

At week 48, participants receiving VCV had a median drop in viral load of between -1.44 and -1.92 log₁₀, and a median increase in CD4 cell count of between 96 cells/mm³ (for patients taking the 15mg dose) and 130 cells/mm³ (for those randomised to take the 10mg dose). These values are similar to those reported at week 24. Data for the placebo group was unavailable, as there were only five participants in the group at week 48.

The percentage of participants achieving an undetectable viral load with VCV ranged from 27% to 37%, compared with 11% in the placebo arm. Moreover, in the 20 participants receiving VCV and with an undetectable viral load at 24 weeks, 70% remained undetectable at 48 weeks.

Patients had the option of commencing therapy with T-20. Of the VCV-treated patients who opted to initiate T-20 therapy, the best drops in viral load were observed in patients who had never taken T-20 before (mean decrease in viral load, -2 log₁₀).

Virologic failure occurred in 27% of patients taking the 10mg dose of VCV and 35% of those on the 15mg dose. This contrasted to 86% of participants receiving placebo who experienced virological failure. Of 26 VCV participants with virologic failure, nine (35%) had virus that had switched from an R5 tropism to an X4 or mixed/dual tropism.

Data were presented on the patients who changed HIV tropism during VCV therapy. The original study design excluded these patients from further analysis. However, it was subsequently decided to allow then to continue VCV therapy if their physician thought it worthwhile. CD4 cell count and viral load in these individuals remained broadly stable after the change in tropism.

Two additional malignancies amongst VCV-treated patients were reported since the 24-week data were presented in Toronto. At 24-weeks, six cases of cancer had been observed amongst VCV-treated patients compared to two in the placebo arm (one of these patients had briefly been treated with a 10mg dose of VCV). Dr R Gulick, who presented the data, said that VCV’s relationship with cancer remained uncertain because of the small number of cases. Other serious adverse events were similar across all arms, and no seizures were reported.