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Small Study Suggests Once-Daily MVC Plus ATV/r as Viable First Regimen
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
IAC: Once-Daily Maraviroc (MVC) + Atazanavir/Ritonavir(ATV/r) vs. Emtricitabine/Tenofovir(TDF/FTC) + ATV/r in Treatment Naïve Patients: A Week 24 Planned Interim Analysis - (07/22/10)
A 121-person study found similar virologic responses with once-daily maraviroc and once-daily tenofovir/emtricitabine (TDF/FTC)--both with atazanavir/ritonavir--after 24 weeks [1]. The trial will run for 48 weeks but does not have the statistical power to demonstrate noninferiority of the maraviroc regimen to the standard three-drug combination. Two people stopped the maraviroc combo because of side effects, while none stopped the comparator regimen for that reason.
Although licensed as a twice-daily antiretroviral, the CCR5 antagonist maraviroc yields higher concentrations when given with most protease inhibitors (PIs). Regimens including maraviroc or raltegravir plus a boosted PI have emerged as potential first-line combinations that would avoid the toxicities of nucleosides and the nucleotide TDF. But such regimens would have to be given once daily to match the convenience of combinations containing TDF/FTC or abacavir/lamivudine.
Clinical investigators in the United States, Spain, and Germany undertook this open-label trial in previously untreated adults with CCR5-using virus (according to the enhanced Trofile assay), a viral load above 1000 copies, and a CD4 count above 100. No one had virus resistant to study drugs when the trial began. The investigators randomized 60 people to take 150 mg of maraviroc once daily and 61 to take once-daily TDF/FTC, both with once-daily atazanavir/ritonavir.
Average pretreatment viral load stood at 4.6 log copies in the maraviroc group (about 40,000 copies) and 4.7 in the TDF/FTC group (about 50,000 copies). About one quarter of participants starting maraviroc and one third starting TDF/FTC had a viral load above 100,000 when the study began. Starting CD4 counts averaged 344 in the maraviroc arm and 358 in the TDF/FTC arm. Three quarters of study participants in both arms were men, and age averaged 38.3 in the maraviroc group and 35.3 in the TDF/FTC group.
At a planned 24-week interim analysis, 48 people (80%) taking maraviroc and 54 taking TDF/FTC (88.5%) had a viral load below 50 copies in a discontinued-equals-failure analysis. Virologic response rates did not differ substantially between the two arms among people who began treatment with a viral load above 100,000 copies (81% with maraviroc and 77% with TDF/FTC). CD4 counts rose by an average 195 with maraviroc and 173 with TDF/FTC.
Two discontinuations for side effects in the maraviroc group contributed to the slightly higher failure rate because no one stopped the TDF/FTC regimen for side effects. But altogether 5 people discontinued the maraviroc regimen and 4 quit the TDF/FTC regimen by week 24.
Ten people taking TDF/FTC (16.4%) and 5 taking maraviroc (8.3%) had a serious adverse event, but none of these problems in the maraviroc arm could be attributed to that drug. There were 20 grade 3 or 4 adverse events with maraviroc (33.3%) versus 13 with TDF/FTC (21.3%). One malignancy and one category C event developed in the maraviroc group, numbers identical to those in the TDF/FTC group. There were 16 grade 3 or 4 cases of hyperbilirubinemia in the maraviroc group (26%) and 8 (13%) in the TDF/FTC group.
A phase 3 trial of maraviroc plus atazanavir/ritonavir is planned.
Reference
1. Mills A, Mildvan D, Podzamczer D, et al. Safety and immunovirological activity of once daily maraviroc (MVC) in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine 200mg/tenofovir 300mg QD (TDF/FTC) + ATV/r in treatment-naïve patients infected with CCR5-tropic HIV-1 (Study A4001078): a week 24 planned interim analysis. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract THLBB203.
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