ICAAC: 48-week results show maraviroc still potent in highly treatment-experienced

Forty-eight week results from the MOTIVATE 1 study of maraviroc in highly treatment-experienced patients show viral suppression is still being maintained in the majority of patients who added the drug to optimised background therapy. The findings were presented this week at the 47^th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago.

The CCR5 antagonist maraviroc (Celsentri) is being studied in two ongoing clinical trials (MOTIVATE 1 and 2) in treatment-experienced patients. It was recently approved for use in treatment-experienced patients in the United States and Europe.

MOTIVATE 1 recruited patients from Canada and the US, and randomised patients to receive maraviroc at one of two doses (300 mg once daily, or 150 mg twice daily) or placebo. Everyone in the study received an optimised background therapy (OBT) combination selected according to resistance profiles.

Eligibility criteria and baseline characteristics of participants in this study have been described previously in a report on 24-week results of this study, presented at the Conference on Retroviruses and Opportunistic Infections in February.

Of note, 69% of the once daily maraviroc group and 75% of the twice daily group had two or fewer active drugs in their background regimen, no participants took darunavir/ritonavir and around 10% took tipranavir/ritonavir.

Week 48 results, presented as a late breaker on Tuesday, show that although the proportion of patients with undetectable viral load has declined slightly since week 24 in the maraviroc treatment groups, the majority of patients still have viral load below 400 copies/ml, and continue to enjoy sustained CD4 cell gains (+113 and 122 cells/mm³ for the once and twice daily groups respectively).

In summary, 57.5% of those receiving the twice-daily dose of maraviroc had viral load below 400 copies/ml at week 48, and 46.8% had viral load below 50 copies/ml.

In comparison 22% of the placebo group had viral load below 400 copies/ml at week 48, and 16% viral load below 50 copies/ml.

Participants in the study were stratified by baseline viral load (above and below 100,000 copies/ml), and according to previous exposure to T-20 (enfuvirtide) (the only agent in a new drug class available at the time the study began).

Among those with no previous history of T-20 use, and who included the drug in their background regimen, 61% in the twice daily arm had viral load below 50 copies/ml at week 48, compared to 32% of those who had already used T-20. Seventy-one per cent of enfuvirtide-naïve patients had viral load below 400 copies/ml.

When analysed according to baseline viral load, those with baseline viral load below 100,000 copies/ml were much more likely to have viral load below 50 copies/ml at week 48 (60% vs 32%).

Safety analyses continue to show no unexpected adverse events, and no difference between the placebo group and maraviroc group in rates of discontinuation due to adverse events (around 6%) or in serious adverse events (grade 3-4) (around 17%).