Efficacy and safety of once-daily (QD) compared with twice-daily (BID) maraviroc plus optimized background therapy (OBT) in treatment-experienced patients infected with CCR5-tropic-HIV-1: 24-week combined analysis of the MOTIVATE 1 and 2 studies
Objectives: Maraviroc, a CCR5 antagonist, plus OBT demonstrated significantly greater virologic and immunologic efficacy and a similar safety profile compared to OBT plus placebo, in two double-blind studies in treatment-experienced patients – MOTIVATE 1 (USA/Canada) and MOTIVATE 2 (Europe/Australia/USA). A planned 24-week analysis of pooled data was conducted.
Methods: Patients with triple-class-drug-experience and/or triple-class-drug-resistance, CCR5-tropic-HIV-1 only (Trofileä), and HIV-1-RNA ³5000 copies/mL were randomized 1:2:2 to OBT (3–6 ARVs +/- low-dose ritonavir; darunavir/r not permitted) plus placebo, maraviroc 300mg QD or BID. Endpoints included change from baseline in HIV-1-RNA (primary) and proportion of subjects achieving <400/<50 copies/mL (secondary) at week-24. Subgroup analyses by screening HIV-1-RNA, baseline CD4 count, and number of active drugs in OBT regimen were conducted.
| ||PBO + OBT: % <50 / <400 copies/mL||MVC QD + OBT: % <50 / <400 copies/mL||MVC BID + OBT: % <50 / <400 copies/mL|
|OVERALL||23% / 28% (N=209)||44% / 55% (N=414)||45% / 61% (N=426)|
|No active drugs in OBT (based on genotypic/phenotypic test results)||3% / 6% (N=35)||18% / 26% (N=51)||29% / 41% (N=56)|
|Baseline CD4 count <50 cells/mm3||3% / 5% (N=37)||11% / 20% (N=85)||20% / 31% (N=85)|
|Screening HIV-1-RNA ³100,000 copies/mL||11% / 16% (N=84)||28% / 45% (N=170)||35% / 52% (N=176)|
Primary and secondary endpoint analyses demonstrated superior virologic and immunologic efficacy of each maraviroc group vs. placebo. Although the studies were not designed to compare maraviroc QD to BID, a greater number of patients in certain subgroups receiving maraviroc BID achieved virologic suppression, including patients with no active drugs in OBT, low CD4 (baseline), or high HIV-1-RNA (screening). Pooled analyses demonstrated similar safety profiles for BID and QD groups versus placebo, with no increased hepatotoxicity with maraviroc compared to placebo, including hepatitis B and C co-infected patients, and no imbalance in malignancies (either AIDS or non-AIDS associated).
Conclusions: Maraviroc plus OBT demonstrated statistically greater efficacy and similar safety to placebo plus OBT in this pooled 24-week analysis. In selected sub-populations there were higher rates of virologic suppression with maraviroc BID than with maraviroc QD.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
"GulickR.M., et al.
Efficacy and safety of once-daily (QD) compared with twice-daily (BID) maraviroc plus optimized background therapy (OBT) in treatment-experienced patients infected with CCR5-tropic-HIV-1: 24-week combined analysis of the MOTIVATE 1 and 2 studies.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: