Important note: Information in this article was accurate in August 2007. The state of the art may have changed since the publication date.
HIV Treatment Bulletin - Vol. 8, No. 8/9, August-September 2007
Simon Collins, HIV i-Base
Two late breaker posters at the meeting presented additional results for maraviroc in treatment-experienced patients.
Elna van der Ryst from Pfizer analysed 24 week efficacy results from the combined Phase III Motivate 1 and 2 studies, by screening genotypic, phenotypic and overall susceptibility scores to OBT, as well as by first-time use of selected background drugs.[1]
Efficacy results, including response by number of active drugs, were presented at CROI this year, and were reported in the March/April issue of HTB.[2]
In these studies, CCR5-tropic patients with triple-class-experience and/or resistance, and HIV-1-RNA >5000 copies/mL were randomised 2:2:1 to OBT (3–6 ARVs ±low-dose ritonavir) plus maraviroc QD, BID or placebo.
Viral response by use of active lopinavir/r or T-20 is detailed in Table 1.
| Table 1: Viral response by use of active T-20 or lopinavir/r | |||
| Placebo + OBT <50 / <400 copies/mL |
Maraviroc QD + OBT <50 / <400 copies/mL |
Maraviroc BID + OBT <50 / <400 copies/mL |
|
| Total population | 25% / 30% (n=207) | 48% / 61% (n=408) | 48% / 65% (n=419) |
| T-20 first use/no mutations | 36% / 40% (n=58) | 64% / 75% (n=91) | 53% / 75% (n=109) |
| Lopinavir/r first use/no mutations | 50% / 60% (n=10) | 74% / 96% (n=27) | 70% / 87% (n=23) |
In a second poster, Trip Gulick from Weill Medical College of Cornell University, New York, presented efficacy analysis supporting the decision for maraviroc to be dose twice-daily.[3]
Although tolerability was similar between the two dosing groups, twice-daily dosing provided significantly greater viral suppression, especially for patients with lower baseline CD4, higher baseline viral load, and fewer active drugs in the background regimen (see Table 2).
| Table 2: Virological efficacy of QD vs BID maraviroc | |||
| 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 viral load >100,000 copies/mL |
11% / 16% (n=84) | 28% / 45% (n=170) | 35% / 52% (n=176) |
Comment
The underperformance in important patient subgroups (low CD4, high viral load, and fewer active drugs in the regimen) clearly supported the choice to develop maraviroc as a twice-daily drug.
References
| 1. | van der Ryst E, Cooper D, Konourina I et al. Efficacy of maraviroc in combination with at least one other potent new antiretroviral drug: 24week combined analysis of the MOTIVATE 1 and 2 studies. IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: (Abstract No. WEPEB115LB). |
| 2. | See: Maraviroc Phase2b/3 results in treatment-experienced CCR5-tropic patients. HIV Treat Bull 2007 Mar/Apr. |
| 3. | Gulick RM, van der Ryst E, Lampiris H et al. Efficacy and safety of once-daily (QD) compared with twice-daily (BID) maraviroc plus optimised background therapy (OBT) in treatment-experienced patients infected with CCR5-tropic-HIV-1: 24-week combined analysis of the MOTIVATE 1 and 2 studies. IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: (Abstract No. WEPEB115LB). |
2007-08-10
IB070808-08
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