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A Look Back at Once-Daily 150-mg Maraviroc
for Experienced in MOTIVATE Trials
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
When given with any boosted protease inhibitor (PI) except tipranavir or fosamprenavir, once-daily maraviroc at a dose of 150 mg controlled viral replication as well as twice-daily 150-mg maraviroc in a retrospective analysis of 48-week data from the MOTIVATE trials [1]. That finding held true in people who started treatment with a high viral load or a low CD4 count.
For people planning a rescue regimen with any boosted PI except tipranavir, the MOTIVATE studies randomized patients to once- or twice-daily maraviroc at a dose of 150 mg or to placebo, with an optimized background regimen [2]. This post hoc analysis of MOTIVATE data, presented by David Hardy (University of California, Los Angeles), compared the efficacy of once-daily maraviroc versus twice-daily maraviroc with boosted PIs at study week 48.
The analysis involved 448 people starting a salvage regimen including a boosted PI, 187 randomized to once-daily maraviroc, 176 to twice-daily maraviroc, and 85 to placebo. The boosted PIs considered in this analysis were atazanavir, lopinavir, indinavir, and saquinavir. Everyone had CCR5-using virus according to ESTA, the enhanced Trofile assay. Age averaged 44 to 47 across the three study arms, 88% were men, and about 80% were white. Median initial CD4 counts were 177 in the once-daily arm, 187 in the twice-daily arm, and 167 in the placebo arm. Baseline viral loads were close to 100,000 copies.
At week 48, similar proportions in the once-daily and twice-daily maraviroc groups had a viral load below 50 copies:
--Once daily: 85 of 187, 45.5%
--Twice daily: 84 of 176, 47.4%
--Placebo: 14 of 85, 16.5%
Proportions with a sub-50 load at week 48 after starting the maraviroc regimen with more than 100,000 copies were also similar with once- and twice-daily dosing:
--Once daily: 30 of 78, 38.5%
--Twice daily: 30 of 77, 39%
--Placebo: 6 of 42, 14.3%
Sub-50-copy response rates at 48 weeks were lower in people who began maraviroc with fewer than 50 CD4s, but still comparable between the once-daily regimen and the twice-daily regimen (17.2% and 18.5%).
Among people who started maraviroc with no active drugs in the background regimen (by weighted optimized background regimen susceptibility score), response rates were 35.9% with once-daily maraviroc and 35.7% with twice-daily dosing. Respective response rates for people who began maraviroc with 1 or more active background drugs were 59.7% and 58.1%. In both of these comparisons, response rates were substantially higher with either maraviroc regimen than with placebo.
Hardy and colleagues also looked at people using any boosted PI or atazanavir/ritonavir or lopinavir/ritonavir for the first time in their maraviroc regimen. Again, 48-week sub-50-copy response rates with once-daily maraviroc matched or slightly exceeded rates with twice-daily maraviroc: for any first-time boosted PI, 59.0% once daily and 56.3% twice daily; for first-time atazanavir/ritonavir, 59.4% once daily and 57.1% twice daily; for first-time lopinavir/ritonavir, 69.0% once daily and 58.1% twice daily.
In an earlier assessment of maraviroc trough concentrations in HIV-positive people, the median maraviroc trough in 15 people taking 150 mg of maraviroc once daily with darunavir/ritonavir (800/100 mg once daily) was 50 ng/mL, compared with 48 ng/mL in 12 people taking 300 mg of maraviroc twice daily with tenofovir/emtricitabine [3]. Mean troughs were 65 ng/mL with once-daily 150-mg maraviroc and 48 ng/mL with twice-daily 300-mg maraviroc.
Hardy and colleagues proposed that once-daily maraviroc at 150 mg--taken with any boosted PI except tipranavir or fosamprenavir--"may be a potential option for treatment-experienced patients seeking a simplified treatment regimen."
References
1. Taylor S, Arribas J, Perno CF, et al. Efficacy of maraviroc (MVC) administered once-daily or twice-daily with boosted protease inhibitors to treatment-experienced patients. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUAB0106.
2. Gulick RM, Lalezari J, Goodrich J, et al; MOTIVATE Study Teams. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359:1429-1441. http://www.nejm.org/doi/full/10.1056/NEJMoa0803152.
3. Taylor S, Dufty N, Watson J, et al. MVC 300 mg once daily + DRV/RTV 800/100 mg once daily provides MVC trough concentrations comparable to trough concentrations in HIV-1 patients taking MVC 300 mg twice daily + TVD: implications for phase 3 studies. Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. http://www.retroconference.org/2011/PDFs/636.pdf.
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